Efficacy of early treatment on 52 patients with preneoplastic hepatitis B virus-associated hepatocellular carcinoma by compound Phyllanthus Urinaria L / 中国结合医学杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Identification of tetracenomycin X from a marine-derived Saccharothrix sp. guided by genes sequence analysis / 药学学报

The crude extracts of the fermentation broth from a marine sediment-derived actinomycete strain, Saccharothrix sp. 10-10, showed significant antibacterial activities against drug-resistant pathogens. A genome-mining PCR-based experiment targeting the genes encoding key enzymes involved in the biosynthesis of secondary metabolites indicated that the strain 10-10 showed the potential to produce tetracenomycin-like compounds. Further chemical investigation of the cultures of this strain led to the identification of two antibiotics, including a tetracenomycin (Tcm) analogs, Tcm X (1), and a tomaymycin derivative, oxotomaymycin (2). Their structures were identified by spectroscopic data analysis, including UV, 1D-NMR, 2D-NMR and MS spectra. Tcm X (1) showed moderate antibacterial activities against a number of drug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) pathogens, with the MIC values in the range of 32-64 microg x mL(-1). In addition, 1 also displayed significant cytotoxic activities against human cancer cell lines, including HL60 (leukemia), HepG2 (liver), and MCF-7 (breast) with the IC 50 values of 5.1, 9.7 and 18.0 micromol x L(-1), respectively. Guided by the PCR-based gene sequence analysis, Tcm X (1) and oxotomaymycin (2) were identified from the genus of Saccharothrix and their 13C NMR data were correctly assigned on the basis of 2D NMR spectroscopic data analysis for the first time.

Advances in the study of affinity selection-ultrafiltration/HPLC-MS / 药学学报

Affinity selection-ultrafiltration/HPLC-MS is the combination of the ultrafiltration and HPLC-MS, mainly used for screening small active molecular substances from combinatorial libraries and natural product extracts, which can bind to solution-phase targets. Besides, it can be used in metabolic screening and characterization of ligand-receptor binding. It is a complement to the traditional methods of screening and identifying drugs. This review describes its principle and application in drug study.

Preneoplastic markers of hepatitis B virus-associated hepatocellular carcinoma and their significance in clinical settings / 中华肝脏病杂志

<p><b>OBJECTIVES</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Bacterial resistance and study of new antibiotics / 中国医学科学院学报

Drug-resistant (including multidrug-resistant) bacteria increase continuously with the wide use of antibiotics, which have seriously threatened the human health. It is an important way to fight against drug-resistance by screening and developing novel drugs based on the various mechanisms of the bacterial drug tolerances. Meanwhile, the basic research related to the new drug R. & D. and studies on the new screening methods for the antimicrobial agents should be taken seriously and strengthened, so as to accelerate the process of finding new drugs and meet the challenge of new pathogens and new drug-resistant strains.

Drug screening model acting on out-membrane protein OprM in pseudomonas aeruginosa efflux pump system / 中国医学科学院学报

<p><b>OBJECTIVE</b>To establish an efflux pump inhibitor screening model with the out-membrane protein OprM in Pseudomonas aeruginosa efflux pump system as the target point.</p><p><b>METHODS</b>Efflux pump out-membrane protein gene oprM was obtained from standard Pseudomonas aeruginosa PA01 strain. Expression of OprM protein was induced in E. coli strain HS151 with T-easy vector as the cloning vector, and pMMB67EH as the expression vector. In order to evaluate the function of OprM protein, we measured intracellular tetracycline concentrations with liquid scintillation counter, measured the diameters of bacteriostatic circles with paper disc, and then established a screening model accordingly.</p><p><b>RESULTS</b>OprM protein was highly expressed. Using Pseudomonas aeruginosa as the main detecting bacteria, we established a drug screening model acting on OprM. A total of 1 600 microbial fermentation samples were screened with this model, among which 56 positive strains were found, with a positive rate of 3.5%.</p><p><b>CONCLUSION</b>OprM plays an important role in drug efflux. The established model has good specificity and maneuverability.</p>

Clone and expression of isocitrate lyase gene in Mycobacterium tuberculosis H37Rv / 中国医学科学院学报

<p><b>OBJECTIVE</b>To construct recombinant plasmid with isocitrate lyase (ICL) gene of Mycobacterium tuberculosis H37Rv for stable and high level expression of ICL in prokaryotic expression system.</p><p><b>METHODS</b>The recombinant plasmid with ICL gene (pET30 (a)-Rv0467) was constructed by polymerase chain reaction and cloning. The fusion protein was expressed in E. coli host strain BL21 (DE3). Activity of the fusion protein was studied after it was purified with metal chelating chromatography.</p><p><b>RESULTS</b>We constructed the plasmid which could highly express Mycobacterium tuberculosis H37Rv ICL. The plasmid was highly expressed in E. coli BL21 (DE3), in which the fusion protein accounted for 30% of total protein content. After having been purified by metal chelating chromatography, the purity of the soluble fusion protein was 90%. The fusion protein had activity of ICL.</p><p><b>CONCLUSION</b>Using the prokaryotic expression system, the ICL gene of Mycobacterium tuberculosis H37Rv was successfully cloned and expressed, which build the basis for screening new anti-tuberculosis drugs with ICL as the target point.</p>

A Clinical Trial of Paroxetine and Psychotherapy in Patients with Poststroke Depression and Anxiety / 中国心理卫生杂志

Objective:To study the efficacy of paroxetine and psychotherapy in patients with poststroke de- pression and anxiety.Methods:81 patients who met the CCMD-3 criteria of depression and anxiety after acute brain stroke were recruited and randomized into 3 groups.Group A was treated with routine antistroke medication and paroxetine;Group B was treated with routine antistroke medications,paroxetine plus psychotherapy;Group C(con- trol)was treated with routine antistroke medication.All patients were treated for 6 weeks and evaluated with SSS, HAMD,HAMA as measures of efficacy and side effects.Results:The comorbidity rate of poststroke depression and anxiety was 65.9%.According to the reduction of SSS,HAMD and HAMA scores,and increase of BI score,signifi- cant improvement has been showed in all patients.There was significant difference among group A,B and the control group(P