Construction of a genome instability-derived lncRNA-based risk scoring system for the prognosis of hepatocellular carcinoma.

Emerging evidence revealed the critical roles of long non-coding RNAs (lncRNAs) in maintaining genomic instability. However, genome instability-associated lncRNAs (GILncRNAs) and their performance in clinical prognostic significance in hepatocellular carcinoma (HCC) are rarely reported. Our study constructed a computational framework integrating somatic mutation information and lncRNA expression profiles of HCC genome and we identified 88 GILncRNAs of HCC. Function enrichment analysis revealed that GILncRNAs were involved in various metabolism processes and genome instability of cancer. A genome instability-derived lncRNA-based gene signature (GILncSig) was constructed using training set data. The performance of GILncSig for outcome prediction was validated in testing set and The Cancer Genome Atlas (TCGA) set. The multivariate cox regression analysis and stratification analysis demonstrated GILncSig could serve as an independent prognostic factor for the overall survival of HCC patients. The time-dependent Receiver Operating Characteristic (ROC) curve illustrated GILncSig outperformed two recently published lncRNA signatures for overall survival prediction. The combination of GILncSig and tumor protein p53 (TP53) mutation status exhibited better prognostic performance in survival evaluation compared to TP53 mutation status alone. AC145343.1 was further validated to be a risk factor for HCC in vitro among GILncSig. Overall, our study provided a novel approach for identification of genome instability-associated lncRNAs and established an independent risk score system for outcome prediction of HCC patients, which provided a new insight for exploring in-depth mechanism and potential therapy strategy.

Long-term follow-up of cumulative incidence of hepatocellular carcinoma in hepatitis B virus patients without antiviral therapy.

BACKGROUND: China has a high prevalence of hepatitis B virus (HBV), but most chronic hepatitis B (CHB) patients do not receive standardized antiviral therapy. There are few relevant reports addressing the outcomes of the large number of CHB patients who do not receive antiviral therapy. AIM: To observe the outcomes of long-term follow-up of patients with CHB without antiviral treatment. METHODS: This study included 362 patients with CHB and 96 with hepatitis B cirrhosis without antiviral treatment and with only liver protection and anti-inflammatory treatment from 1993 to 1998. The median follow-up times were 10 and 7 years, respectively. A total of 203 CHB and 129 hepatitis B cirrhosis patients receiving antiviral therapy were selected as the control groups. The median follow-up times were 8 and 7 years, respectively. Kaplan-Meier curves were used to analyze the cumulative incidence of hepatocellular carcinoma (HCC), and the Cox regression model was used to analyze the risk factors for HCC. RESULTS: Among the patients in the non-antiviral group, 16.9% had spontaneous decreases in HBV DNA to undetectable levels, and 32.8% showed hepatitis B e antigen (HBeAg) seroconversion. In the antiviral group, 87.2% of patients had undetectable HBV DNA, and 52% showed HBeAg seroconversion. Among CHB and hepatitis B cirrhosis patients, the cumulative incidence rates of HCC were 14.9% and 53.1%, respectively, in the non-antiviral group and were 10.7% and 31.9%, respectively, in the antiviral group. There was no difference between the two groups regarding the CHB patients (P = 0.842), but there was a difference between the groups regarding the hepatitis B cirrhosis patients (P = 0.026). The cumulative incidence rates of HCC were 1.6% and 22.3% (P = 0.022) in the groups with and without spontaneous HBeAg seroconversion, respectively. The incidence rates of HCC among patients with and without spontaneous declines in HBV DNA to undetectable levels were 1.6% and 19.1%, respectively (P = 0.051). There was no difference in the cumulative incidence of HCC between the two groups regarding the patients with drug-resistant CHB (P = 0.119), but there was a significant difference between the two groups regarding the patients with cirrhosis (P = 0.004). The Cox regression model was used for regression of the corrected REACH-B score, which showed that alanine aminotransferase > 400 U/L, history of diabetes, and family history of liver cancer were risk factors for HCC among men aged > 40 years (P < 0.05). Multifactorial analysis showed that a family history of HCC among men was a risk factor for HCC. CONCLUSION: Antiviral therapy and non-antiviral therapy with liver protection and anti-inflammatory therapy can reduce the risk of HCC. Antiviral therapy may mask the spontaneous serological response of some patients during CHB. Therefore, the effect of early antiviral therapy on reducing the incidence of HCC cannot be overestimated.

Bioinformatics Analyses of Potential miRNA-mRNA Regulatory Axis in HBV-related Hepatocellular Carcinoma.

Aims: We aimed to explore the crucial miRNA-mRNA axis through bioinformatics analysis and provide evidences for the development of pathophysiological mechanisms and new therapies for HBV-related HCC. Methods: MiRNA (GSE76903) and mRNA (GSE77509) dataset were used to screen differentially expressed miRNAs (DE-miRNAs) and differentially expressed mRNAs (DE-mRNAs) using R software. Overlapping genes between DE-mRNAs and target genes of DE-miRNAs were identified as candidate genes. Hub genes were obtained via cytohubba analysis. The expression at protein and mRNA levels and prognostic value of hub genes were evaluated based on The Cancer Genome Atlas (TCGA) data. Key miRNA-mRNA axes were constructed according to predicted miRNA-mRNA pairs. MiRNA expression and prognostic role were respectively identified using starBase v3.0 and Kaplan-Meier plotter database. Real-time PCR was performed to verify the expression of crucial miRNAs and mRNAs. Coexpression of crucial miRNA and mRNA were analyzed using starBase v3.0. Results: CDK1, CCNB1, CKS2 and CCNE1 were screened as hub genes, which were significantly upregulated at protein and mRNA levels. These up-regulated hub genes were also significantly associated with poor prognosis. Hsa-mir-195-5p/CDK1, hsa-mir-5589-3p/CCNB1 and hsa-let-7c-3p/CKS2 were screened as critical miRNA-mRNA axes. Critical miRNAs were decreased in HCC, which indicates unfavourable prognosis. QPCR results showed that crucial miRNAs were decreased, whereas critical mRNAs were increased in HBV-related HCC. A reverse relationship between miRNA and mRNA in crucial axis was further verified. Conclusion: This study identified several miRNA-mRNA axes in HBV-related HCC. Hsa-mir-195-5p/CDK1, hsa-mir-5589-3p/CCNB1 and hsa-let-7c-3p/CKS2 might serve as potential prognostic biomarkers and therapeutic targets for HBV-related HCC.

Efficacy of a Chinese herbal formula on hepatitis B e antigen-positive chronic hepatitis B patients.

BACKGROUND: No guideline recommends antiviral therapy for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients with persistently normal alanine aminotransferase levels and a high hepatitis B virus (HBV) DNA viral load. AIM: To evaluate the feasibility and safety of a Chinese herbal formula as a therapeutic option for chronic HBV infection. METHODS: In total, 395 patients (30-65 years old) with confirmed HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase were randomized to receive either Chinese herbal formula or placebo for 96 wk. Endpoints to evaluate therapeutic efficacy included: (1) HBV DNA levels decreased to less than 4 log10 IU/mL at weeks 48 and 96; and (2) HBeAg clearance and seroconversion rates at weeks 48 and 96. RESULTS: HBV DNA levels ≤ 4 log10 IU/mL were 10.05% at week 48 and 18.59% at week 96 in the treatment group. The HBeAg clearance and conversion rates were 8.54% and 8.04% at week 48 and 16.08% and 14.57% at week 96, respectively. However, HBV DNA levels ≤ 4 log10 IU/mL were 2.55% and 2.55% at weeks 48 and 96, respectively, and the HBeAg clearance rates were 3.06% and 5.61% at weeks 48 and 96, respectively, in the control group. The quantitative hepatitis B surface antigen and HBeAg levels at baseline and changes during the treatment period as well as the alanine aminotransferase elevation at weeks 12 and 24 were strong predictors of HBeAg clearance. CONCLUSION: High rates of HBV DNA reduction, HBeAg clearance and seroconversion could be achieved with Chinese herbal formula treatments, and the treatments were relatively safe for HBeAg-positive chronic hepatitis B-infected patients with persistently normal alanine aminotransferase. The ability of the compound to modulate host immune function probably contributed to this effect.

Clinical and histopathological features of chronic hepatitis B virus infected patients with high HBV-DNA viral load and normal alanine aminotransferase level: A multicentre-based study in China.

BACKGROUND: The aim of this study is to reveal the clinical and histopathological features of HBsAg-positive and HBeAg-positive chronic hepatitis B infected patients with high level of HBV DNA, from 17 hospitals and medical centres in China, with alanine aminotransferase levels within the lower region of normal range versus those with levels within the upper region of normal range and to investigate the clinical risk factors for the requirement of treatment through the examination of liver biopsy. METHODS: Liver biopsy was performed on high level of HBV DNA of 455 patients with HBsAg-positive and HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase level. Liver necroinflammation and fibrosis were graded per the Knodell histological activity index and Ishak's fibrosis score, respectively. Univariate analysis of the clinical parameters versus necroinflammation and fibrosis was carried out. RESULTS: Of the subjects in this multicentre-based study, 5.49% and 10.11% had significant necroinflammation with Knodell histological activity index ≥ 9 and hepatic fibrosis stages with Ishak scores ≥ 3, respectively. The subjects were stratified into three age groups (30-39, 40-49 and ≥ 50 years), and our data clearly suggested that age, particularly in the age group over 50, was an independent predictor of liver necroinflammation and fibrosis. Lower HBV-DNA viral levels were found in patients with Knodell histological activity index ≥ 9 or advanced fibrosis (Ishak scores ≥ 3). CONCLUSION: Our results showed that histological changes in liver tissues were observed in a significant proportion of patients with persistently normal alanine aminotransferase level. According to the data evaluation results, liver biopsy is advisable for HBeAg-positive chronic hepatitis B infected patients aged older than 40 and high HBV-DNA viral load in China.

Shugan Xiaozhi Decoction Attenuates Nonalcoholic Steatohepatitis by Enhancing PPARα and L-FABP Expressions in High-Fat-Fed Rats.

This study aimed to investigate the effects of Shugan Xiaozhi decoction (SX) on nonalcoholic steatohepatitis (NASH) induced by high-fat diet in rats. The rats were randomly divided into 6 groups, namely, control, model, fenofibrate, and three different dosage of SX (10, 20, and 40 g/kg/day, p.o.). After establishing the NASH model, at 8 weeks of the experiment, treatments were administrated intragastrically to the fenofibrate and SX groups. All rats were killed after 4 weeks of treatment. Compared with the model group, alanine aminotransferase (ALT), aspartate aminotransferase (AST), free fatty acid (FFA), total cholesterol (TC), triacylglycerol (TG), and low-density lipoprotein cholesterol (LDL) serum in the serum were significantly reduced in all SX treatment groups in a dose-dependent manner. Evidence showed that SX could protect the liver by upregulating the gene and protein expressions of peroxisome proliferator-activated receptor alpha (PPARα) and liver fatty acid binding protein (L-FABP) in a dose-dependent manner. Chemical constituents of SX were further analyzed by ultraperformance liquid chromatography coupled with electrospray ionization mass spectrometry (UPLC-ESI-MS) and 30 chemicals in the ethanolic extract were tentatively identified. To conclude, our results clearly indicated that SX could protect liver functions and relieve hepatic steatosis and inflammation.

Efficacy of early treatment on 52 patients with preneoplastic hepatitis B virus-associated hepatocellular carcinoma by compound Phyllanthus Urinaria L.

OBJECTIVE: To observe the change in the number of antibodies of preneoplastic hepatocellular carcinoma (HCC) using early treatment by Compound Phyllanthus Urinaria L. (CPUL) on patients with preneoplastic hepatitis B virus (HBV)-associated HCC. METHODS: A total of 102 cirrhosis patients with regenerative or dysplastic nodules whose sera were tested positive for at least one of these six proteins (five up-regulated genes URG4, URG7, URG11, URG12 and URG19, and one down-regulated gene DRG2) were assigned randomly to two groups using continual random codes by SPSS software. Fifty-two patients were in the treatment group and 50 patients were in the control group. CPUL was used in the treatment group for 3 years, while the control group did not receive any treatment. The changes in HBV-DNA level, number of antibodies, and hepatocarcinogenesis occurred were observed. Patients who did not develop HCC were followed up for another 2 years. RESULTS: HBV-DNA levels decreased ⩾2log in 22.2% (10/45) of patients in the treatment group in contrast to only 5.0% (2/40) of patients in the control group (P=0.0228). The number of antibodies that were tested positive in the treatment group (1.08±1.01) was significantly lower compared with the control group (2.11±1.12) after 24 months of drug treatment (P<0.01). Both the positive rates of anti-URG11 (33/52) and anti-URG19 (31/52) were over 60% at baseline in the two groups, and were decreased to 48.1% (25/52) and 46.2% (24/52) respectively at 36 months of drug treatment, while the rates increased to 68.0% (34/50) and 66.0% (33/50) respectively (P=0.0417, P=0.0436) in the control group. The positive rate of anti-DRG2 was increased to 55.8% (29/52) at 36 months of drug treatment, while in the control group was decreased to 36.0% (18/50, P=0.0452). Among the 102 patients who developed HCC, 2 were in the treatment group and 9 were in the control group, meaning that a significant difference between the two groups (P=0.0212). In 11 patients who developed HCC, anti-URG11 and anti-URG19 were always positive, while anti-DRG2 was negative. Patients newly developing HCC were 6 (20.0%) in the control group, and only one (2.5%) in the treatment group (P=0.0441) during 2-year follow-up after the end of the treatment. CONCLUSIONS: Anti-URG11, anti-URG19 and anti-DRG2 could be used as early markers in the prediction of the therapeutic efficacy of CPUL in treating preneoplastic HCC. CPUL is useful in preventing or delaying the development of HBV-associated cirrhosis to HCC.

Two new acetylated flavonoid glycosides from Phyllanthus urinaria.

Two new acetylated flavonoid glycosides, quercetin 3-O-α-l-(2,4-di-O-acetyl) rhamnopyranoside-7-O-α-l-rhamnopyranoside (1) and quercetin 3-O-α-l-(3,4-di-O-acetyl) rhamnopyranoside-7-O-α-l-rhamnopyranoside (2), together with two known compounds, quercetin (3) and quercetin 3-O-α-l-rhamnopyranoside (4), were isolated from the ethanol extract of Phyllanthus urinaria. The structures of the new compounds were determined on the basis of extensive spectroscopic data including IR, HR-ESI-MS, 1D NMR, and 2D NMR.

Efficacy of ursodeoxycholic acid combined with Tongdan Decoction () on immunological indices and histopathological changes in primary biliary cirrhosis patients.

OBJECTIVE: To observe the efficacy of ursodeoxycholic acid (UDCA) combined with Tongdan: Decoction () on immunological indices and histopathological changes in patients with primary biliary cirrhosis (PBC) of IIor III histological stage. METHODS: Sixty PBC patients were assigned randomly and equally: to the control group treated with UDCA alone and the treatment group treated with UDCA combined with Tongdan Decoction. The immunological indices and histopathological changes were detected before and after 24-week treatment, and the follow-up lasted for 1-3 years. RESULTS: After 24-week treatment, CD4(+)CD28(-) in the peripheral blood was lowered and CD4(+)CD25(+) was increased in both groups, and better effect was shown in the treatment group (P<0.01). The levels of IgM, IgG, and IgA decreased markedly after 96-week treatment in the treatment group (P< 0.05, P< 0.01), while in the control group, only the latter two showed significant decrease after 148 week (all P<0.05). At the end of the 3-year follow-up, the medians of histopathological

[Combined therapy of shehuang paste and colonic dialysis with Chinese medicines for treatment of refractory cirrhotic ascites complicated with azotemia].

OBJECTIVE: To observe the clinical efficacy of combined therapy of Shehuang Paste (SHP) with colonic dialysis in treating patients with refractory cirrhotic ascites complicated with azotemia. METHODS: Adopting a multi-centered, randomized, double blinded and 1:1 parallel controlled trial, 120 patients were equally randomized into 2 groups, the control group was treated by conventional basic therapy (umbilical application of placebo paste and colonic dialysis with normal saline), and the treatment group by, besides the same basic therapy, umbilical application of SHP once a day and colonic dialysis with herbal medicine once every other day. The course was 1 month for both groups. Changes of ascites volume, renal function, serum and urinary levels of Na+ and K+, blood vasoactive substance, and portal dynamics in patients before and after treatment were observed. RESULTS: The total effective rate for ascites was 71.7% (43/60 cases) in the treatment group and 18.3% (11/60 cases) in the control group, showing significant difference between groups (P < 0.01). Significant difference of blood creatinine, urea nitrogen, serum Na+ levels, and urinary Na+/K+ ratio were shown in the treatment group (P < 0.01) before and after treatment, and between groups after treatment (P < 0.05, P < 0.01). Portal vein blood flow was significantly lowered in the treatment group after treatment (P < 0.01), which showed significant difference as compared with that in the control group (P < 0.01). Besides, levels of atrial natriuretic peptide, renin, angiotensin, nitric oxide, and aldosterone decreased and endotoxemia improved remarkably in the treatment group (P < 0.01). One-year follow-up showed that the ascites eliminating rate and the incidence of hepato-renal syndrome in the treatment group was 38.3% (23/60 cases) and 23.3% (14/60 cases) respectively, while in the control group 0 and 41.7% (25/60 cases) respectively, all showed statistical difference between groups (all P < 0.05). CONCLUSION: Combined therapy of SHP and colonic dialysis with herbal medicine could effectively eliminate the ascites, improve the hemodynamic condition of portal and splenic veins, reduce the content of vasoactive substance and noxious substances like ammonia and endotoxin in blood, and lower the incidence of hepato-renal syndrome.

[Preneoplastic markers of hepatitis B virus-associated hepatocellular carcinoma and their significance in clinical settings].

OBJECTIVES: To identify serologic markers that may indicate the early presence of hepatocellular carcinoma (HCC), and analyze their significance in the pathogenesis of chronic hepatitis B. METHODS: Hepatitis B x antigen (HBxAg) positive and negative HepG2 cells were subjected to PCR select cDNA subtraction to identify differentially expressed genes that may precede the development of HCC. These included the up-regulated genes URG4, URG7, URG11, and VEGFR3, and the down-regulated gene, Sui1. Specific ELISAs were constructed to measure differentially expressed antigens and their corresponding antibodies to determine whether they had prognostic and/or diagnostic value. The study population consisted of 730 people. Among them, 416 were HBsAg(-) and 298 were HBV carriers with chronic liver disease and/or HCC. In addition, 16 patients had non-viral hepatitis. Among these, serial serum samples from 53 HBsAg(+) patients with cirrhosis were collected and studied. RESULTS: Antibodies to multiple differentially regulated genes were detectable in serum samples from patients with HBV associated cirrhosis and HCC, but not in serum samples from uninfected individuals (P < 0.01). Antibodies were undetectable in serum samples from HBV patients without liver disease and in serum samples from patients with other tumor types, and among those with non viral hepatitis. Among patients at high risk of developing HCC, these antibodies were found to be independent of nationality and ethnicity. Statistical analysis of the 28 HBsAg(+) patients with HCC showed that anti-URG11 and anti-VEGFR3 were the most frequently detected antibodies. These antibodies were found to coexist in 16 (P < 0.05). In contrast, among the 25 HBsAg(+) patients without HCC, anti-Sui1 and anti-URG7 were the most prevalent antibodies. These antibodies coexisted in 11 (P < 0.05). In addition, HCC patients with four or more antibodies detected before the appearance of HCC had a poorer survival outcome. CONCLUSION: These antibodies can be detected in serum samples several months to several years before the appearance of HCC. This suggests that they may be preneoplastic markers that may help to distinguish which HBV carriers with cirrhosis are most likely to progress and develop HCC.

[Preventive and therapeutic effects of qiongyugao on hepatocellular carcinoma via inhibition of the expression of HBxAg in hepatic carcinoma cells].

AIM: To investigate the effects of qiongyugao on the expression of hepatitis B x antigen (HBxAg) in BALB/c-nu mice into which human hepatic carcinoma cells were transplanted, and to analyze its specific mechanism in prophylaxis and treatment of hepatocellular carcinoma. METHODS: A nude mouse model with the transplantation of human hepatic carcinoma cells was established to observe the preventive and therapeutic effects of qiongyugao on the body weight and tumor weight of the mice. The expression of HBxAg in tumor and liver tissue wsa detected by immunohistochemical studies. RESULTS: Compared with model control group, prophylaxis and treatment with qiongyugao increased the body weight, depressed the tumor weight and inhibited HBxAg expression. The same efficacy was showed in both qiongyugao prophylaxis group and cyclophosphamide treatment group. CONCLUSION: Qiongyugao can slow down the growth of tumor and inhibit the expression of HBxAg, which may be an essential mechanism in prophylaxis and treatment of hepatocellular carcinoma.

Antiviral effect of Chinese medicine jiaweisinisan in hepatitis B virus transgenic mice.

AIM: To study the antiviral effect of Chinese medicine jiaweisinisan (JWSNS) on hepatitis B virus (HBV) infection in transgenic mice (TGM). METHODS: Twenty two 6-8 wk old HBV TGM in the third generation were divided into TGM control group and TGM treated group randomly. The normal control group included ten normal BC 57L/6 mice at the same age. The mice in treated group were administrated with JWSNS at the concentration of 4 g/mL and the dosage of 50 g/kg per d for 30 d, while the mice in TGM control group and normal control group were administrated with normal saline at the same dosage and the same time. Polymerase chain reaction (PCR) was used to assess the contents of HBV DNA in serum of HBV TGM before and after treatments, whereas blot hybridization was utilized to measure the contents of HBV DNA in the liver of both HBV TGM and normal BC 57L/6 mice. RESULTS: The levels of serum HBV DNA in TGM treated group were remarkably decreased after the treatment of JWSNS (7.662+/-0.78 vs 5.22+/-3.14, P < 0.05), while there was no obvious change after administration of normal saline in TGM control group (7.125+/-4.26 vs 8.932+/-5.12, P > 0.05). The OD values of HBV DNA in the livers of the mice in TGM treated group were significantly lower than those of TGM control group (0.274+/-0.096 vs 0.432+/-0.119, P < 0.01). CONCLUSION: JWSNS exerts suppressive effects on HBV DNA in the serum and liver of TGM.

Clinical research on navel application of Shehuang Paste combined with Chinese herbal colon dialysis in treatment of refractory cirrhotic ascites complicated with azotemia.

AIM: To explore the efficacy and mechanism of a novel therapeutic method of traditional Chinese medicine in patients with refractory cirrhotic ascites complicated with azotemia. METHODS: Seventy-five cases of refractory cirrhotic ascites complicated with azotemia were randomly divided into 3 groups: comprehensive treatment (n = 29), simple treatment (n = 24), and control (n = 22). The basic treatment methods were the same in all groups, including liver protecting medicines, diuretics and supportive drugs. The control group underwent only the basic treatment. Shehuang Paste (SHP) was applied to the navels of the two treatment groups once a day for 30 d. Colon dialysis with Chinese herbs was administered to the comprehensive treatment group once every two days. Before and after treatment, we measured abdominal circumference, BUN, Cr, serum Na+, urine Na+/K+, liver function, endotoxin content, NO, and ET-1. Color Doppler ultrasonography was conducted to measure the portal vein blood flow. RESULTS: The total effective rate for ascites was 72.4% in the comprehensive treatment group, 45.8% in the simple treatment, contrasting with 18.2% in the controls. Between the two treatment groups and the controls, there were significant differences in the effective rates (P < 0.01, and P < 0.05). There was also a significant difference (P < 0.05) between the two treatment groups. Measurements of Cr and BUN showed higher values for the treatment groups, with the comprehensive better than the simple group (P < 0.05). Sera Na, urine Na/K were different, P < 0.01 between pre- and post-treatment in the comprehensive group, and P < 0.05 in the simple group. The treatment groups' endotoxin content was also significantly reduced (P < 0.01, and P < 0.05), with the comprehensive group better than the simple group (P < 0.05). Portal vein blood flow and NO content significantly reduced (P < 0.05), as did ET-1 content (P < 0.01). There were no significant changes in the control group (P > 0.05). The comprehensive treatment group's pre- and post-treatment portal vein and splenic vein blood flows showed a positive correlation to NO, ET-1 and endotoxin contents. CONCLUSION: When treating refractory cirrhotic ascites complicated with azotemia, Shehuang Paste combined with Chinese herbal dialysis is better than Shehuang Paste alone for ascites resolution, azotemia, and endotoxin elimination. However, both methods on their own were also effective for reducing portal and splenic vein blood flow, and lowering the contents of NO, ET-1 in the two treatment groups.

Effects of Shehuang Paste on hemodynamics, endotoxin, nitric oxide and endothelin-1 in patients with refractory cirrhotic ascites.

OBJECTIVE: To explore the influence of Shehuang Paste (SHP) to the hemodynamics, endotoxin, nitric oxide (NO), and endothelin-1 (ET-1) in patients with refractory cirrhotic ascites. METHODS: Fifty-nine cases of refractory cirrhotic ascites were randomly assigned to two groups, 32 cases in the treatment group and 27 cases in the control group. The basic treatment was the same for both groups, including liver protecting medicines, diuretics and supportive drugs, but SHP navel sticking was applied for the treatment group additionally once a day. A course of one month of treatment was applied and the general efficacy on ascites was observed by the end of the therapeutic course. Before and after the treatment, examinations by limulus lysate chromogenic test was conducted to measure plasma endotoxin content; colorimetry to measure plasma content of NO indirectly, radioimmunoassay to measure plasma ET-1 content; and color Doppler ultrasonography to measure the blood flow of portal vein and splenic vein. The relationship between the blood flow of portal vein and splenic vein and endotoxin, NO and ET-1 in the treatment group was analyzed as well. RESULTS: The total effective rate on ascites was 84.4% in the treatment group, and 48. 1% in the control group, with significant difference shown between them (P<0.01). In the treatment group the blood flow of portal vein and splenic vein, contents of endotoxin, NO and ET-1 all got significantly reduced after treatment ( P<0.05 or P<0.01); while these indexes in the control group were not significantly changed ( P 0.05). Moreover, it was found that in the treatment group, the blood flow of portal vein and splenic vein had a positive correlation to the levels of NO, ET-1, and endotoxin, either before or after treatment. CONCLUSION: Application of SHP navel sticking could clearly reduce the blood flow of portal vein and splenic vein, and lower the content of endotoxin, NO and ET-1. The blood flow of portal vein and splenic vein in the treatment group showed a positive correlation with the contents of endotoxin, NO and ET-1. liver cirrhosis, refractory ascites, vasoactive substance, hemodynamics

[Clinical study on treatment of liver fibrosis by different dosages of Salvia injection].

OBJECTIVE: To find the optimal dosage of Salvia injection in treating chronic hepatitis B caused liver fibrosis. METHODS: Sixty-four patients, whose diagnosis was confirmed as chronic hepatitis B caused liver fibrosis and differentiated by TCM typing as blood stasis blocking Collaterals type, were selected and randomly divided by lottery method into the large, middle and small dose of SI treated groups and the control group. All the patients were treated with modified Gexia Zhuyu Decoction, to the patients in the SI groups, 24 ml, 16 ml and 8 ml of SI were additionally administered by intravenous dripping respectively. The therapeutic course was 45 days. The clinical symptoms and signs; liver functional indexes as alanine transaminase (ALT), aspartate aminotransferase (AST) and albumin (ALB); and liver fibrosis indexes as procollagen type III (PC-III), collagen type IV (C-IV) and hyaluronic acid (HA), were measured before and after treatment. RESULTS: Different dosages of SI all could improve the clinical symptoms, and lower levels of ALT, AST, HA, PC-III and C-IV. Treatment of large dosage SI showed the best efficacy, superior to that of middle and small dosage SI, but no significant difference was found between the efficacy of the latter two. CONCLUSION: Anti-liver fibrosis effect of large dosage SI is better than that of middle or small dosage SI.