A novel RAV transcription factor from pear interacts with viral RNA-silencing suppressors to inhibit viral infection.

In plants, RNA silencing constitutes a strong defense against viral infection, which viruses counteract with RNA-silencing suppressors (RSSs). Understanding the interactions between viral RSSs and host factors is crucial for elucidating the molecular arms race between viruses and host plants. We report that the helicase motif (Hel) of the replicase encoded by apple stem grooving virus (ASGV)-the main virus affecting pear trees in China-is an RSS that can inhibit both local and systemic RNA silencing, possibly by binding double-stranded (ds) siRNA. The transcription factor related to ABSCISIC ACID INSENSITIVE3/VIVIPAROUS1 from pear (PbRAV1) enters the cytoplasm and binds Hel through its C terminus, thereby attenuating its RSS activity by reducing its binding affinity to 21- and 24-nt ds siRNA, and suppressing ASGV infection. PbRAV1 can also target p24, an RSS encoded by grapevine leafroll-associated virus 2 (GLRaV-2), with similar negative effects on p24's suppressive function and inhibition of GLRaV-2 infection. Moreover, like the positive role of the PbRAV1 homolog from grapevine (VvRAV1) in p24's previously reported RSS activity, ASGV Hel can also hijack VvRAV1 and employ the protein to sequester 21-nt ds siRNA, thereby enhancing its own RSS activity and promoting ASGV infection. Furthermore, PbRAV1 neither interacts with CP, an RSS encoded by grapevine inner necrosis virus, nor has any obvious effect on CP's RSS activity. Our results identify an RSS encoded by ASGV and demonstrate that PbRAV1, representing a novel type of RAV transcription factor, plays a defensive role against viral infection by targeting viral RSSs.

[Evaluation of chemical constituents of Draconis Sanguis and its protective effect on renal tubular injury in diabetic kidney disease].

The chemical constituents of Draconis Sanguis were preliminarily studied by macroporous resin, silica gel, dextran gel, and high-performance liquid chromatography. One retro-dihydrochalcone, four flavonoids, and one stilbene were isolated. Their chemical structures were identified as 4-hydroxy-2,6-dimethoxy-3-methyldihydrochalcone(1), 4'-hydroxy-5,7-dimethoxy-8-methylflavan(2), 7-hydroxy-4',5-dimethoxyflavan(3),(2S)-7-hydroxy-5-methoxy-6-methylflavan(4),(2S)-7-hydroxy-5-methoxyflavan(5), and pterostilbene(6) by modern spectroscopy, physicochemical properties, and literature comparison. Compound 1 was a new compound. Compounds 2 and 6 were first found in the Arecaceae family. Compound 5 had the potential to prevent and treat diabetic kidney disease.

Propeller Configuration Flipping of the Trivalent Boron-Inducing Substituent Dependence of the Circularly Polarized Luminescence Sign in Triarylborane-Based [7]Helicenes.

We here disclose two triarylborane-based [7]helicenes, which contain a dimesitylboryl or a 2-(dimesitylboryl)phenyl at position 9 of the [7]helicene skeleton. The change in the peripheral substituent from dimesitylboryl to 2-(dimesitylboryl)phenyl induced doubling of |glum| and sign inversion of the circularly polarized luminescence (CPL). The substituent dependence of the CPL sign is reasonably explained by the propeller configuration flipping of boron, which has a significant influence on the chiroptical properties.

Sesquiterpenoids from Artemisia argyi and their NO production inhibitory activity in RAW264.7 cells.

Investigation into the chemical diversity of Artemisia argyi led to the discovery of two new (1, 4) and four known (2-3, 5-6) sesquiterpenoids. The new structures were determined via extensive spectroscopic data, including IR, UV, MS, and NMR, and the absolute configurations of these compounds were elucidated by calculated ECD method. All isolates were tested for their inhibitory activity against NO production in RAW 264.7 macrophages, and the isolated sesquiterpenoids exhibited NO production inhibitory activity with IC50 values ranging from 1.91 to 36.52 µM.

A Review on Classification and Biological Activities of Alkaloids from the Genus Zanthoxylum Species.

Many plants in the genus Zanthoxylum, belonging to the Rutaceae family, are used as folk medicines for the treatment of various diseases, which have gained much attention for their phytochemical and pharmacological activity investigations. Alkaloids are the largest secondary metabolites with structurally diverse types found in this genus and they demonstrate a wide range of biological activities. The aim of this review is to provide a summary on the isolation, classification, and biological properties of alkaloids from Zanthoxylum species, which also will bring more attention to other researchers for further biological study on alkaloids for the new drug development.

1,10-seco guaianolide-type sesquiterpenoids from Chrysanthemum indicum.

ABSTACTA chemical investigation of the whole plant of traditional Chinese medicine, Chrysanthemum indicum L., led to the discovery of six guaianolide-type sesquiterpenoids 1-6 with a 1,10-splited skeleton. The structure of the new compound 1 was established by extensive analysis of UV, IR, MS, NMR and ECD data. Compounds 3-6 are mutually stereoisomers with four chiral centers and their absolute configurations were determined by comparison of ECD spectra. The anti-inflammatory effects of these isolates on lipopolysaccharide (LPS)-induced nitric oxide (NO) were investigated in RAW 264.7 cells. Results showed that most of the compounds displayed NO production inhibitory activities with IC50 values ranged from 3.54 to 8.17 µM.

CO2 or air cholangiography reduces the risk of post-ERCP cholangitis in patients with Bismuth type IV hilar biliary obstruction.

BACKGROUND: Endoscopic biliary stenting by endoscopic retrograde cholangiopancreatography (ERCP) is the most common form of palliation for malignant hilar obstruction. However, ERCP in such cases is associated with a risk of cholangitis. The incidence of post-ERCP cholangitis is particularly high in Bismuth type IV hilar obstruction, and this risk is further increased when the contrast injected for cholangiography is not drained. The present study aims to compare the incidence of cholangitis associated with the use of a contrast agent, air and CO2 for cholangiography in type IV hilar biliary lesions. METHODS: The clinical data of consecutive 70 patients with type IV hilar obstruction, who underwent ERCP from October 2013 to November 2017, were retrospectively analyzed. These patients were divided into three groups based on the agent used for cholangiography: group A, contrast (n = 22); group B, air (n = 18); group C, CO2 (n = 30). These three methods of cholangiography were chronologically separated. Prior to the ERCP, MRCP was obtained from all patients to guide the endoscopic intervention. RESULTS: At baseline, there was no significant difference in terms of the patient's age, gender, symptoms and liver function tests among the three groups (P > 0.05). The complication rates were significantly higher in group A than in groups B and C (63.6% vs. 26.7 and 27.8%, P < 0.05). The incidence of post-ERCP cholangitis was significantly higher in group A (P < 0.05), while the incidence of post-ERCP pancreatitis and bleeding were similar in the three groups. After the ERCP, the mean hospital stay was shorter in groups B and C, when compared to group A (P < 0.05). However, there was no significant difference in the 30-day mortality rate among the three groups (P > 0.05). Furthermore, there was no significant difference between groups B and C in terms of primary end points. CONCLUSION: CO2 or air cholangiography during ERCP for type IV hilar obstruction is associated with reduced risk of post-ERCP cholangitis, when compared to conventional contrast agents.

Platinum ions mediate the interactions between DNA and carbon quantum dots: diagnosis of MRSA infections.

In this study, we have developed a rapid and cost-effective method employing platinum ion (Pt4+)-capped fluorescent carbon quantum dots (CQDs) coupled with loop-mediated isothermal amplification (LAMP) to detect dual MRSA genes. We synthesized nitrogen- and chlorine-co-doped fluorescent CQDs (CQDSPDs) from spermidine trihydrochloride via a simple one-step pyrolysis. The CQDSPDs capped with Pt4+ ions through the cooperative coordination of the amine and chlorine groups on the surface of CQDs facilitated the double-stranded DNA (dsDNA)-induced fluorescence quenching of CQDs, and enabled the construction of the CQDSPDs/Pt4+ probe for the detection of as few as 10 copies of the MRSA gene (mecA and femA). The sensitivity and specificity of the CQDSPDs/Pt4+ probe for MRSA detection in clinical specimens (n = 24) were 94% and 86%, respectively. Our results reveal that the CQDSPDs/Pt4+ probe has great potential for the diagnosis of antibiotic-resistant superbugs with high sensitivity, specificity, and agreement.

Effects of Portulaca Oleracea Extract on Acute Alcoholic Liver Injury of Rats.

The present study was envisaged to investigate the chemical constituents and the intervention effects of Portulaca oleracea extract (POE) on acute alcoholic liver injury of rats. The chemical composition of POE was detected by high performance liquid chromatography (HPLC). Sixty male Wistar rats were divided into 6 groups: Normal control (NC) group, acute alcoholic liver injury model group (ALI), low, medium and high dose of POE (25, 50, 100 mg/kg) groups and bifendate (BF, 3.75 mg/kg) group. Each group was given by intragastrical administration for 7 days. Alcoholic liver injury was induced in the experimental model by administering 50% ethanol at 8 mL/kg and repeated administration after 6 h, for a period of 7 days. The results showed that pretreatment with POE significantly reduced the ethanol-elevated serum level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and triglyceride (TG). The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in liver were enhanced followed by administration of POE, while the content of nitric oxide (NO) and malondialdehyde (MDA) was found to decrease. Hepatic content of tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) was also reduced by POE treatment. These results indicated that POE could increase the antioxidant capacity and relieve the inflammatory injury of the liver cells induced by ethanol. Meanwhile, in our study, POE reduced the expression of miR-122, acetyl coenzyme A carboxylase (ACC) 1 mRNA and protein and increased the expression of lipoprotein lipase (LPL) mRNA and protein in liver, which indicated that POE could improve the lipid metabolism disorder induced by ethanol. Our findings suggested that POE had protective effects on acute alcoholic liver injury of rats.

DNA Modulates the Interaction of Genetically Engineered DNA-Binding Proteins and Gold Nanoparticles: Diagnosis of High-Risk HPV Infection.

Gene detection has an important role in diagnosing several serious diseases and genetic defects in modern clinical medicine. Herein, we report a fast and convenient gene detection method based on the modulation of the interaction between a heat-resistant double-stranded DNA (dsDNA)-binding protein (Sso7d) and gold nanoparticles (Au NPs). We prepared a recombinant Cys-Sso7d, which is Sso7d with an extra cysteine (Cys) residue in the N-terminus, through protein engineering to control the interaction between Sso7d and Au NPs. Cys-Sso7d exhibited a stronger affinity for Au NPs and more easily induced the aggregation of Au NPs than Sso7d. In addition, Cys-Sso7d retained its ability to bind with dsDNA. The aggregation of Au NPs induced by Cys-Sso7d was diminished in the presence of dsDNA, which could be utilized as a transduction mechanism for the detection of the polymerase chain reaction (PCR) products of human papillomavirus (HPV) gene fragments (HPV types 16 and 18). The Cys-Sso7d/Au NP probe could detect as few as 1 copy of the HPV gene. The sensitivity and specificity of the Cys-Sso7d/Au NP probe for Pap smear clinical specimens (n = 52) for HPV 16 and HPV 18 detection were 85.7%/100.0% and 85.7%/91.7%, respectively. Our results demonstrate that the Cys-Sso7d/Au NP probe can be used to diagnose high-risk HPV types in Pap smear samples with high sensitivity, specificity, and accuracy.

Analysis of homozygosity disequilibrium using whole-genome sequencing data.

Homozygosity disequilibrium (HD), a nonrandom sizable run of homozygosity in the genome, may be related to the evolution of populations and may also confer susceptibility to disease. No studies have investigated HD using whole genome sequencing (WGS) analysis. In this study, we used an enhanced version of Loss-Of-Heterozygosity Analysis Suite (LOHAS) software to investigate HD through analysis of real and simulated WGS data sets provided by Genetic Analysis Workshop 18. Using a local polynomial model, we derived whole-genome profiles of homozygosity intensities for 959 individuals and characterized the patterns of HD. Generalized estimating equation analysis for 855 related samples was performed to examine the association between patterns of HD and 3 phenotypes of interest, namely diastolic blood pressure, systolic blood pressure, and hypertension status, with covariate adjustments for age and gender. We found that 4.48% of individuals in this study carried sizable runs of homozygosity (ROHs). Distributions of the length of ROHs were derived and revealed a familial aggregation of HD. Genome-wide homozygosity association analysis identified 5 and 3 ROHs associated with diastolic blood pressure and hypertension, respectively. These regions contain genes associated with calcium channels (CACNA1S), renin catalysis (REN), blood groups (ABO), apolipoprotein (APOA5), and cardiovascular diseases (RASGRP1). Simulation studies showed that our homozygosity association tests controlled type 1 error well and had a promising power. This study provides a useful analysis tool for studying HD and allows us to gain a deeper understanding of HD in the human genome.

Clinical-pathological analysis of hepatitis B virus recurrence after liver transplantation in Chinese patients.

BACKGROUND AND AIM: Liver transplantation (LT) for hepatitis B virus (HBV)-related disease can be complicated by HBV recurrence. The aim of this study was to evaluate the risk factors, prophylaxis treatment, and histological characteristics of HBV recurrence after LT when using long-term, low-dose hepatitis B immunoglobulin (HBIG) plus nucleoside analog (lamivudine [LAM] or entecavir [ETV]). METHODS: Retrospective data from 253 adult LT patients using long-term, low-dose HBIG plus nucleoside analog after LT, for a mean treatment duration of 1-72 months, were collected from a single center in Beijing, China. Univariate analyses were conducted to determine the association among gender, age, hepatocellular carcinoma, hepatitis B e antigen-positive status, HBV-DNA level and tyrosine-methionine-aspartate-aspartate (YMDD) mutations on HBV recurrence in these patients. RESULTS: Overall, the HBV recurrence rate was 6.32% (16/253). There was no significant difference in the survival rate between the HBV recurrence and non-recurrence groups. Risk factors for HBV recurrence were: hepatitis B e antigen positivity, HBV-DNA > 10(5) copies/mL, hepatocellular carcinoma, and YMDD mutation. Sixteen patients receiving LAM had HBV recurrence (16/169; mean treatment duration: 61.8 ± 18.3 months). No HBV recurrence occurred in patients receiving ETV after LT (0/84; mean treatment duration: 57.1 ± 15.9 months). Differences in rate of mortality and HBV recurrence were not significant between the two groups. CONCLUSIONS: LT is an effective treatment for HBV-related end-stage liver disease. The combination of ETV and intramuscular HBIG for HBV recurrence prophylaxis after LT was more effective than LAM, especially in Chinese patients with HBV recurrence risk factors.

[A multicenter study of the effectiveness of interferon alpha-1b (Hapgen) in treating HBeAg positive chronic hepatitis B patients].

To compare the efficacy and safety of interferon a-1b and interferon a-1b combined with lamivudine in the treatment of HBeAg positive chronic hepatitis B (CHB), to analyze the impact of variable factors on the efficacy, and to investigate the individualized anti-viral regimen for CHB patients. 111 CHB patients were enrolled and randomly divided into two groups. Group A: patients received interferon a-1b (49 patients, 50mug I. M. , qod. ) , Group B: interferon a-1b (idem) combined with lamivudine for 6-12 months or longer(62 patients, 100 mg, P.O. , q.d. ). (1) The HBeAg seroconversion rates of treatment by 12 and 18 months were 28.6% and 36.7% in group A, 29.0% and 38.7% in group B, respectively, no significant difference found between the two groups at the end of treatment (x2=0.003, P value is more than 0.05; x2=1.500, P value is more than 0.05). (2) The HBV DNA undetectable rates of treatment by 6 months, 12 months and 18 months were 8.2%, 53.1% and 57.1% in group A, 66.1%, 83.9% and 88.7% in group B, respectively, still no significant difference existed between the two groups (x2=38.150, P value is less than 0.05; x2=12.073, P value is less than 0.05, x2=14.459, P value is less than 0.05). (3) In group A, the HBeAg seroconversion rates for male and female patients were 34.5% and 40.0% respectively, no significant difference found between. As regard ages the rates were 34.9% and 50.0% for patients younger or more than 40 years of age, no significant difference existed between. The HBeAg seroconversion rate was higher in patients with lower baseline serum HBV DNA loads ( less than 6 log10 copies/ml) . (4) The rates of patients with fever and blood abnormality were 36.7% and 34.7% in group A, 32.3% and 27.4% in group B, respectively. The total incidences of adverse events were similar between group A and B (x2=0.244, P value is more than 0.05; x2=0.682, P value is more than 0.05). (5) The ratio of drug resistance in group B was only 1.6%. The adverse events of interferon a-1b treatment for CHB are low and mild. The HBeAg seroconversion rate persistently raises with the extension of interferon a-1b treatment course. The HBV DNA undetectable rate of interferon a-1b combined with lamivudine is significantly higher than that of interferon a-1b and the drug resistance of lamivudine can be reduced obviously by combination therapy.

[Therapeutic effect of autologous cytokine-induced killer cells on patients with liver cirrhosis caused by HBV infection].

OBJECTIVE: To observe the therapeutic effect of autologous cytokine-induced killer cells (CIK) on HBV DNA positive patients with liver cirrhosis. METHODS: HBV DNA positive 33 patients with cirrhosis were treated with CIK. Before and after cultured in vitro and post-treatment, CD3+, CD3+CD4+, CD3+CD8+, CD3+CD56+ cells, mDC and pDC were detected by flow cytometry. The indexes of virus and liver function were compared between pre- and post-treatment. RESULTS: CD3+, CD3+CD8+ cells and CD3+CD56+ cells were higher after cultured in vitro and after transfused back than those before culture (91.5 +/- 10.3, 74.4 +/- 9.9 vs. 67.9 +/- 12.8; 60.9 +/- 15.5, 37.3 +/- 15.1 vs. 27.9 +/- 10.9; 18.4 +/- 11.7, 14.5 +/- 7.5 vs. 10.6 +/- 7.1). The percentages of mDC and pDC also increased after-treatment vs. pre-treatment (0.54 +/- 0.18 vs. 0.70 +/- 0.29; 0.26 +/- 0.13 vs. 0.41 +/- 0.25). HBV DNA became undetectable in 12 patients and decrease exceeded 100 times in 4 patients after treatment. HBeAg became undetectable in 10 of 14 patients who were HBeAg positive pretreatment patients, among them 2 patients had HBeAb sero conversion. The liver function was improved after treatment. All patients tolerated the treatment. CONCLUSION: CIK treatment can increase immune effector cells and has some antiviral effect and is safe.

[Clinical profiles of circulating dendritic cell phenotype and lymphocyte subsets in patients chronically infected with HBV during lamivudine treatment].

BACKGROUND: To investigate the changes of circulating dendritic cell (DC) and lymphocytes subsets in chronic hepatitis B patients treated with lamivudine. METHODS: Sixteen chronic hepatitis B patients treated with lamivudine were included and followed up for 48 weeks in this study. Before and during lamivudine treatment, DC collected from peripheral blood sample was cultured in vitro and surface markers of DC and lymphocytes subsets were detected by flow cytometry simultaneously. RESULTS: Of the 16 patients, 11 were consistently HBV DNA negative in serum and HBV DNA YMDD variants appeared in 5 cases. In the consistent responder group, HLA-DR level of DC decreased transiently in 12 weeks and recovered in 48 weeks (P<0.05). At 48 weeks CD80, CD40 and CD1a were improved compared with baseline level (P<0.05). In the YMDD variant group, CD83 and HLA-DR level of DC decreased at 12 weeks treatment (P<0.05) and HLA-DR was still lower compared with baseline (P<0.05). In the consistent responder group, no significant changes occurred in lymphocyte subsets number at 12 weeks treatment, but CD4 + T cell was improved and NK cell dropped at 48 weeks compared with baseline level (P<0.05). In the YMDD variant group lymphocyte subsets had no statistically significant change. CONCLUSION: In the consistent responder group, the expression of surface costimulatory molecules of DC, such as CD80 and CD40,was partly recovered after the virus of hepatitis B had been inhibited efficiently, HLA-DR levels of DC decreased transiently at 12 weeks and recovered in 48 weeks and CD4+ T cell improved and NK cell dropped at 48 weeks. In the YMDD variant group, HLA-DR levels of DC were lower consistently during treatment compared with baseline level.

Decreased numbers and impaired function of circulating dendritic cell subsets in patients with chronic hepatitis B infection (R2).

BACKGROUND AND AIM: To investigate the frequencies, numbers and function of circulating dendritic cell (DC) subsets in patients with hepatitis B virus (HBV) infection, we assayed the circulating precursor DC subsets (including pDC1 and pDC2) and their ability in patients at various stages of HBV infection in vitro. METHODS: Circulating pDC1 and pDC2 frequencies in peripheral blood mononuclear cells (PBMC) were analyzed by flow cytometric analysis. Costimulatory molecule expression and allostimulatory mixed lymphocyte reaction (AMLR) of DC1, cultured from PBMC in vitro, were detected in patients with chronic hepatitis B (CHB). On behalf of pDC2, interferon (IFN)-alpha production of PBMC was determined by the ELISA method in HBV-infected patients. RESULTS: The number of circulating pDC1 decreased only in patients with liver cirrhosis (LC) compared with that in normal controls. However, pDC2 numbers decreased in both CHB and LC patients. DC1 from CHB patients showed lower expression of costimulatory molecules CD80, CD86 and impaired allostimulatory mixed lymphocyte reaction (AMLR) compared with those in normal controls. The ability of PBMC to secrete IFN-alpha also decreased significantly in patients with chronic HBV infection. CONCLUSIONS: Our results suggest that patients with chronic HBV infection have a significantly lower expression of costimulatory molecules and impaired AMLR of pDC1, as well as decreased number and impaired function of circulating pDC2, which may be partially related to HBV disease progression in these patients.

Decreased frequency and function of circulating plasmocytoid dendritic cells (pDC) in hepatitis B virus infected humans.

The Type 2 precursor plasmacytoid dendritic cells (pDC) represent the most important cell type in antiviral innate immunity. To understand the function of pDC during hepatitis B virus infection, the frequency and function of circulating pDC were analyzed by flow cytometric analysis, and IFN-alpha secretion of total PBMCs was determined by ELISA assay in 25 healthy subjects and 116 patients at various stages of chronic hepatitis B virus infection (CHB). The number of circulating pDC was found to be significantly lower in patients with CHB and associated liver cirrhosis (LC). The ability of PBMCs to secrete IFN-alpha also decreased significantly. There was a corresponding decrease of circulating NK cells and CD8+ T cells. We observed that lamuvidine antiviral therapy restored the number of circulating pDC and there was a reversal of pDC frequency with the control of HBV replication in chronic HBV patients, indicating these subjects are unlikely to be totally immunocompromised. The decrease of pDC was found to be related to nosocomial infections in LC patients. Our results suggest that CHB patients probably have a quantitative and qualitative impairment of circulating pDC or NK cells, which may be associated with HBV persistent infection as well as the nosocomial infections that arise in LC patients.

[A prospective study on short period antibiotic treatment of hepatic failure complicated with spontaneous bacterial peritonitis].

BACKGROUND: To observe the effects of short-term antibiotic treatment in patients with hepatic failure and spontaneous bacterial peritonitis (SBP). METHODS: In this prospective study short-term antibiotic treatment was given to 67 cases diagnosed as hepatic failure with spontaneous bacterial peritonitis. Ceftriaxone 2 g, iv drip, q12h for 10 d or ofloxacin 0.2 g, iv drip, q12h for 10 d was given to the patients at random and the efficacy was evaluated on the basis of clinical symptoms, medical examination and ascites after 3, 7, 10 days of therapy. RESULTS: Seven cases (10.44%) were cured and 57 cases (85%) were improved after 3 days therapy, the total effective rate was 95.52%, but in 3 cases the therapy had no effect. The results of ascites bacterial culture and drug susceptibility test showed that one case had drug resistance to ceftriaxone and two cases had drug resistance to ofloxacin, so antibiotics were changed in time. After 7 days therapy, the results showed that 65 cases (97.01%) cured and 2 cases (2.99%) were improved, the total effective rate was 100%. When the therapy lasted for 10 days, all patients were cured. One patient had oral mucous membrane. Candida albicans infection after 3 days therapy; two cases got thrush and one patient got fungal intestinal infection after 7 days therapy; when the therapy lasted for 10 days, 4 cases had thrush and 2 cases had fungal infection of intestines and one patient had pulmonary fungal infection. CONCLUSION: The optimal period of antibiotic treatment of hepatic failure with SBP should be from 7 days to 10 days.

[IFN or oxymatrine in combination with lamivudine in patients with lamivudine-resistant chronic hepatitis B].

OBJECTIVE: To observe the therapeutic efficacy of IFN or oxymatrine in combination with lamivudine in patients with lamivudine-resistant chronic hepatitis B. METHODS: Forty patients ongoing treatment with lamivudine were randomized to three groups: group A, 14 patients with addition of IFN alpha-2b 3MU to ongoing lamivudine, daily, one month, followed by the same dose given every other day, five months; group B, 15 patients with addition of injectable oxymatrine 60 mg daily, three months, followed by oral oxymatrine every day, three months, and group C, 11 patients ongoing treatment with lamivudine alone. The HBV DNA level in serum, HBeAg seroconversion, and ALT level were detected at the end of the treatment. RESULTS: After 6 months of treatment, HBV DNA became negative in 35.73% patients treated with combination with IFN, and in 13.3% patients treated with combination with oxymatrine. ALT level was normal in 85.71% or 86.66% of patients, respectively. In none of the patients under ongoing treatment with lamivudine alone HBV DNA or HBeAg became negative, and ALT level was normal in 36.36% of patients. CONCLUSION: These data indicated that IFN or oxymatrine in combination with ongoing lamivudine therapy provided effective antiviral therapy in patients with lamivudine-resistant HBV. The addition of IFN or oxymatrine to ongoing lamivudine therapy in lamivudine-resistant patients led to significant inhibition of viral replication and improvement in liver function after 6 months of therapy.