Research advance on structure and function of amides in Zanthoxylum plants / 中国中药杂志

Zanthoxylum belongs to the Rutaceae family, and there are 81 Zanthoxylum species and 36 varieties in China. Most of the Zanthoxylum plants are used as culinary spice. In recent years, scholars in China and abroad have carried out in-depth research on Zanthoxylum plants, and found that the peculiar numbing sensation of Zanthoxylum plants originates from amides. It is also determined that amides are an important material basis for exerting pharmacological effects, especially in anti-inflammatory analgesia, anesthesia and other aspects. In this paper, 123 amides in 26 Zanthoxylum plants and their pharmacological activity that have been reported were summarized, which provided scientific reference for the clinical application of Zanthoxylum plants and the research and development of new drugs, and also facilitated the sustainable development and utilization of Zanthoxylum plant resources.

Establishment and Usage of Leukemia-Lymphoma Cell Lines--Review / 中国实验血液学杂志

Cancer cell lines are an indispensable tool in the cancer research. Since the first human cell line, HeLa was established in the 1950s, thousands of cancer cell lines have been established, including 637 characterized leukemia-lymphoma cell lines. The probability to successfully establish cancer cell lines is a low by traditional methods, and the addition of regulatory factors is often required. However, a novel "conditional reprogramming" technology can improve this situction. The establishment and description of a new cell line should be consistent with international guidelines. Cancer cell lines are mainly used in the research of tumor pathogenesis and drug development. Scientists have developed many kinds of cell line panels which can be used for the high-throughput screening of anticancer drugs. Mycoplasma contamination and/or cross-contamination from other cells should be avoided during the use of cell lines. The establishment of a cell model passport database can prevent those misidentifications. In this review, the types, establishment and usage of leukemia-lymphoma cell lines as well as points of attention when using them are summarized briefly.

Effect of Carfilzomib on Proliferation and Apoptosis of Mantle Cell Lymphoma Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of Carfilzomib on mantle cell lymphoma (MCL), and to compare with effect of Bortezomib.@*METHODS@#The Jeko-1 cells and primary MCL cells were treated with Carfilzomib for 24, 48 and 72 h, then the inhibitory rate was detected using CCK-8. Lymphocytes derived from healthy volunteer were served as cell controls. Bortezomib and Cyclophosphamide (CTX) were served as medicinal controls. At the same time, the apoptosis of cells treated with different drugs was detected using flow cytometry.@*RESULTS@#The inhibitory effect of Carfilzomib on Jeko-1 cells and primary MCL cells was exhibited with time-dependent and concentration-dependent manners (P＜0.01, r=0.393, r=0.650, rJ=0.473, r=0.417), but the effect on lymphocytes derived from healthy volunteer only showed time-dependence (P＜0.01, r=0.928). Under the same concentration, Carfilzomib exhibited the proliferation Jeko-1 cells stronger than Bortezomib (P＜0.01), but the same inhibition on primary MCL cells was not significantly different from that on lymphocytes derived from healthy volunteer (P＞0.05). Under clinical recommended concentration, Carfilzomib had a stronger inhibitory effect on primary MCL cells than that of Bortezomib (P＜0.01). Cell apoptosis assay showed that under the same concentration the ability of Carfilzomib to induce cell apoptosis was significantly stronger than that of Bortezomib (P＜0.05).@*CONCLUSION@#Carfilzomib can inhibit the growth of MCL cells, its inhibitory rate on the MCL cells is higher than that of Bortezomib.

Effect of Amino Acid Motifs in Integrin β3 Cytoplasmic Tail on αⅡbβ3-Mediated Cell function in 293T cell models / 中国实验血液学杂志

OBJECTIVE@#To establish 293T cell lines stably expressing Calpain-cleavage related α3 cytoplasmic tail mutants, and to explore the effect of amino acid motifs in integrin β3 cytoplasmic tail on αⅡbβ3-mediated cell function.@*METHODS@#293T cell lines stably co-expressing human wild type integrin αⅡb and full length β3 or mutant β3, including β3-ΔNITY (β3 cytoplasmic tail NITY motif deleted), β3-Δ754 (β3 cytoplasmic tail TNITYRGT motif deleted) and β3-Δ759 (β3 cytoplasmic tail RGT motif deleted) were established. Spreading and adhesion of these stable cell lines on immobilized fibrinogen were tested.@*RESULTS@#293T-αⅡbβ3ΔNITY, 293T-αⅡbβ3Δ754, 293T-αⅡbβ3Δ759 and 293T-αⅡbβ3 cell lines were successfully established. Compared with the 293T cells, 293T-αⅡbβ3 cells which expressed full β3, possessed well adhesion and spread ability on immobilized fibrinogen, suggesting it can be as a surrogate for platelet. Compared with 293T-αⅡbβ3 cells, the 293T-αⅡbβ3ΔNITY cells showed a partial impairment of adhesion and spreadability on immobilized fibrinogen. while the 293T-αⅡbβ3Δ754 cells and 293T-αⅡbβ3Δ759 cells failed to adhere or spread on immobilized fibrinogen.@*CONCLUSION@#To the cell spreading function mediated by integrin β3, RGT motif is vital, while NITY can be dispensable. These established 293T cell lines stably expressing different β3 mutants provide a solid basis for a further analysis of mass spectrometry.

Study on Antioxidant Activity of Different Concentrations of Alcohol Extracts from Paeonia Rockii Pollen / 中国中医药信息杂志

Objective To evaluate the antioxidant activity of different concentrations of alcohol extracts from Paeonia Rockii pollen.Methods The antioxidant activity of different concentrations of alcohol extracts from Paeonia Rockii pollen was evaluated by cupric reducing power method, DPPH radical scavenging activity method and ABTS radical scavenging activity method.Results The amounts of antioxidant activity of gallic acid of anhydrous ethanol extract, 75％ alcohol extract, 50％ alcohol extract, 25％ alcohol extract, and water extract from Paeonia Rockii pollen were 26.00, 28.33, 28.90, 14.98, and 9.24 mg/g, respectively. The sequence of the ability of scavenging DPPH free radical and ABTS radical was Vc > 50％ alcohol extract > 75％ alcohol extract > anhydrous ethanol extract > 25％ alcohol extract > water extract.Conclusion The different concentrations of alcohol extracts from Paeonia Rockii pollen has relatively strong antioxidant activity, especially for 50％ alcohol extract and 75％ alcohol extract.

A study on the correlations study among HOMA-IR, obesity and inflammatory factors among middle aged and elderly population / 预防医学

Objective To investigate the distribution of insulin resistance (HOMA-IR) index and its influencing factorsamong middle and old aged people with normal glucose and to provide the basis for early screening and prevention of type 2diabetes. Methods A total of 229 residents were selected with health records showed normal blood glucose (fasting bloodglucose < 7.0mmol/L, postprandial 2h blood glucose<11.1 mmol/L) and more than 40 years old from July, 2012 to June,2015. Height, weight, waist and hip circumference, and the fasting plasma glucose (FPG), insulin (FINS), lowdensity lipoprotein (LDL), uric acid, tumor necrosis factor (TNF) and interleukin -6 (IL-6) were recorded to analyzethe distribution of HOMA-IR and its influencing factors. Results Totally 229 people were included, of which 113 were male(49.34%), 116 female(50.66%) . The average age was(63.58 + 8.85) years old. The average HOMA-IR index was 0.94(1.08) and there were 21 people that HOMA-IR exceed the standard (HOMA-IR≥2.68), accounting for 9.17%.TheHOMA-IR index of different gender, age, waist circumference, hip circumference, uric acid in the elderly had significantdifference (P < 0.05) .Multiple linear regression analysis showed that HOMA-IR index was positively correlated withfemale, waist circumference and IL-6 and was negatively correlated with age. Conclusion The possibility of IR was higherin women with relatively low age, female, central obesity and high IL-6 levels among the middle and old aged people withnormal blood glucose.

Myr-RKEFAK Peptide Selectively Regulates Outside-in Signaling Transduction-related Functions in Human Platelets / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To study the effect of interaction of the talin rod domain integrin binding site 2 with integrin β3 on platelet signal transduction.</p><p><b>METHODS</b>A peptide that mimics the membrane proximal α helix 6 residues R724 KEFAK729 of the integrin β3 cytoplasmic tails was designed and synthesized, to which the myristoylation was covalently linked to the N-terminal of the peptide enabling membrane penetration. The effects of myr-RKEFAK peptide on the typical platelet outside-in signaling ovent (stable adhesion and spreading on immobilized fibrinogen, aggregation, fibrin clot retraction) and inside-out signaling events (soluble fibrinogen binding) were tested.</p><p><b>RESULTS</b>myr-RKEFAK peptide dose-dependently inhibited platelet stable adhesion and spreading on immobilized fibrinogen, irreversible aggregation, as well as fibrin clot retraction, but not soluble fibrinogen binding and reversible phase of platelet aggregation.</p><p><b>CONCLUSION</b>The cell-penetrating peptide myr-RKEFAK causes an inhibitory effect on integrin β3 outside-in signaling-regulated platelets functions, but did not affect inside-out signaling-regulated platelets functions.</p>

Effect of the Integrin β3 Cytoplasmic NITY Motif on α II bβ3-Mediated Cell Functions in CHO Cell Model / 中国实验血液学杂志

<p><b>UNLABELLED</b>OBJLECTIVE: To investigate the effect of integrin β3 cytoplasmic NITY motif on αIIbβ3-mediated cell functions.</p><p><b>METHODS</b>Stable Chinese hamster ovary (CHO) cell lines that co-express human wild type integrin αIIb and wild type β3 or mutant β3ΔNITY (β3 deleting cytoplasmic NITY motif) were established. Expression of αIIb and β3 were tested by Western blot and flow cytometry in CHO cell lines. Spreading and adhesion of stable cell lines on immobilized fibrinogen were examined. The co-immunoprecipitation was used to detect protein interactions.</p><p><b>RESULTS</b>CHO-αIIbβ3, CHO-αIIbβ3ΔNITY cells were successfully established. The CHO cells transfected with wild type αIIbβ3 had the ability of adhesion and spreading. Compared with CHO-αIIbβ3 cells, CHO-αIIbβ3ΔNITY cells showed an impaired capacity of adhesion but no significant difference was observed in spreading of adhered cells. The co-immunoprecipitation showed that kindlin-2 associated with wild type integrin αIIbβ3. The β3ΔNITY mutation substantially reduced kindlin-2 association.</p><p><b>CONCLUSION</b>Deletion of NITY motif causes an impaired ability of adhesion. The deletion mutation can suppress kindlin-2 binding to integrin β3, thereby partially inhibit the integrin β3 signaling.</p>

Transgenic mouse models of the truncated platelet integrin β3 cytoplasmic tail established by stem cell transplantation / 中国实验血液学杂志

This study was purpose to establish the transgenic mouse models of the truncated platelet integrin β3 by retrovirus-infected hematopoietic stem cells (HSCs) transplantation and to provide the basis for further study of the role of integrin β3 cytoplasmic domain in platelet bi-directional signaling pathways. Wild-type β3, β3-Δ759 (R(760) GT(762) truncated β3) and β3-Δ754 (T(755) NITYRGT(762) truncated β3) cDNAs were subcloned into MSCV MigR1 retroviral vector bearing a GFP gene and packaged into infective retrovirus with BOSC23 cell strain. The bone marrow HSCs of the β3 deficient mice were infected by the retroviruses, and transplanted into lethally-irradiated wild type C57BL/6 mice. GFP positive rate and surface β3 expression of the recipients' platelets at 6 to 8 weeks after transplantation were detected by flow cytometry to evaluate the transgenic efficiency. The results showed that four kinds of transgenic mouse models including vector, wild-type β3, β3-Δ759 and β3-Δ754 were established successfully. GFP positive rates of transgenic mouse platelets ranged from 18% to 66% and the β3 expression of transgenic mouse reached heterozygote (β3(+/-) level of mouse). It is concluded that establishment of transgenic mouse models mediated by retrovirus-infected HSCs transplantation is a feasible, fast, and high throughput transgenic approach and laid a solid foundation for further research on the role of integrin β3 cytoplasmic domain for bi-directional signaling of platelets in vivo, and for the gene therapy of platelet disorders.

Investigation of entecavir treatment in patients with LAM-refractory chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of entecavir (ETV) as a long-term treatment in patients with lamivudine (LAM)-refractory chronic hepatitis B (CHB).</p><p><b>METHODS</b>In this phase II study of ETV-056, 32 CHB patients with resistance to LAM monotherapy were administered ETV at 1.0 mg/day and monitored over a period of 8 years. The virologic, serologic and biochemical responses were measured throughout the treatment course. Outcomes analysis was conducted according to intention-to-treat principles.</p><p><b>RESULTS</b>At baseline and treatment weeks 8, 12, 24, 48, 96, 144, 192, 240, and 420, the proportion of patients with HBV DNA less than 300 copies/ml was 0, 6.3% (2/32), 9.4% (3/32), 18.8% (6/32), 18.8%(6/32), 46.9% (15/32), 43.8% (14/32), 50.0% (16/32), 50.0% (16/32), and 62.5% (20/32). At treatment weeks 48, 96, 168, 192, 240, and 420, the proportion of patients experiencing virological breakthrough was 6.1% (2/32), 9.4% (3/32), 12.5% (4/32), 18.8%(6/32), 25.0%(8/32), and 28.1% (9/32). In the 8 year study period, 32.3% (10/31) of patients achieved HBs seroconversion and four patients achieved HBe seroconversion.</p><p><b>CONCLUSION</b>While treatment with 1.0 mg/day ETV for up to 8 years resulted in mild HBV DNA suppression and increase of HBeAg seroconversion, the safety profile of this therapy was good but the economic cost was high and virological breakthrough rates were high.</p>

Effect of TGF-b1 siRNA-mediated silencing on Smad proteins in hepatic fibrosis rats / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the changes in Smad 2, 3, 4 and 7 of the transforming growth factor-beta 1 (TGF-b1)/Smad signaling pathways in carbon tetrachloride (CCL4)-induced hepatic fibrosis rats treated with TGF-b1 small interfering (si)RNA.</p><p><b>METHODS</b>Rats were randomly divided among five groups: non-fibrotic (normal); fibrosis-induced (model); fibrotic treated with 0.125 mg/kg TGF-b1 siRNA; fibrotic treated with 0.250 mg/kg TGF-b1 siRNA; and fibrotic treated with negative control TGF-b1 siRNA. The expression of Smad 2, 3, 4 and 7 was detected by real-time polymerase chain reaction (for mRNA), immunohistochemistry and Western blotting (for protein).</p><p><b>RESULTS</b>The mRNA and protein levels of Smad 2, 3 and 4 were significantly lower in the the fibrotic rats treated with either 0.250 mg/kg or 0.125 mg/kg TGF-b1 siRNA than in the fibrotic model or the negative control TGF-b1 siRNA rats (P less than 0.01). Moreover, the mRNA and protein expression levels of Smad 2, 3 and 4 were significantly lower in the 0.250 mg/kg TGF-b1 siRNA group than in the 0.125 mg/kg group (P less than 0.05). Comparing the 0.250 mg/kg and 0.125 mg/kg TGF-b1 siRNA groups to the model group and the TGF-b1 siRNA negative control group showed significantly increased levels of mRNA and protein expression of Smad 7 (P less than 0.01). In addition, the expression levels of Smad 7 were significantly higher in the 0.250 mg/kg TGF-b1 siRNA group than in the 0.125 mg/kg group (P less than 0.05).</p><p><b>CONCLUSION</b>siRNA-mediated silencing of TGF-b1 in rats led to significantly reduced expression of Smad 2, 3 and 4, but significantly increased expression of Smad 7. TGF-b1 regulation of Smad signaling molecules may contribute to hepatic fibrosis in rats and represent a target of future therapeutic intervention.</p>

Efficacy of lamivudine on acute-on-chronic liver failure in patients with chronic hepatitis B / 中华肝脏病杂志

To observe the therapeutic effects of lamivudine treatment in patients with early- to mid-stage hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Clinical data of 73 hospitalized patients with HBV-ACLF were retrospectively analyzed. Prothrombin time (PT, active coagulation), HBV DNA, and model for end-stage liver disease (MELD) score data from treatment weeks 4, 8, 24, and 48 were collected and analyzed using the statistical t-test. During the treatment duration, the complete virologic response rates were 57.5% (42/73) at 4 weeks, 71.0% (44/62) at 8 weeks, 83.1% (49/59) at 24 weeks, and 86.5% (45/52) at 48 weeks. The partial virologic response rates were 30.1% (22/73) at 4 weeks, 25.8% (16/62) at 8 weeks, 17.0% (10/59) at 24 weeks, and 13.5% (7/52) at 48 weeks. At week 48, the survival rate was 71.2% (52/73) and the probability of survival was higher in the complete virological response rate (VRR) group than in the partial VRR group [45/73 (61.6%) vs. 7/73 (30.1%), respectively; P = 0.000]. In addition, there were significant improvements in the serum normalization rate of HBV DNA, alanine aminotransferase, aspartate aminotransferase, albumin, total bilirubin, PT and MELD score in surviving patients compared to baseline (P less than 0.05) and in the complete VRR group compared to the partial VRR group (P less than 0.05). Antiviral therapy using lamivudine may be an effective therapeutic option for patients with HBV-ACLF.

Evolution of hepatitis B virus quasispecies during antiviral therapy in one chronic hepatitis B patient / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the evolution of hepatitis B virus (HBV) quasispecies in one patient during lamivudine (LAM) monotherapy and switching to entecavir (ETV) rescue treatment.</p><p><b>METHODS</b>Serum samples were taken at seven different time points during antiviral therapy (0, 24, 48, 60, 72, 96, 152 weeks, respectively), the HBV DNA polymerase gene was amplified, cloned and sequenced to analyze the amino acid substitutions within HBV DNA polymerase gene and distribution of virus quasispecies. Quantitative detection of the HBV wild strains and total virus was performed by amplification refractory mutation system real-time PCR (ARMS-PCR).</p><p><b>RESULTS</b>Three mutation patterns detected during antiviral therapy in the patient: rtM204V, rtM204V+rtL180M and rtM204I. The HBV quasispecies were found always in dynamic variation. The HBV populations were completely replaced with the LAM-resistant variants when the viral breakthrough was encountered during LAM monotherapy. Interestingly, the wild-type variants presented gradually dominant (79.3%) with the decline of HBV DNA load after switching to ETV rescue administration. ARMS-PCR results showed that the wild-type variants account ed for 68.55% of the HBV populations at baseline and this proportion declined to 0.21% when the viral breakthrough emerged under LAM therapy. The wild-type variants gradually increased from week 24 after switching to ETV rescue therapy and the proportion of HBV wild-type variants in the population fluctuated between 16.01% to 26.93%.</p><p><b>CONCLUSIONS</b>The distribution of virus quasispecies were always in dynamic variation during sequential therapy with nucleotide analogs in chronic hepatitis B patients. Different patterns of dynamic HBV quasispecies may have different contribution in ETV resistance in LMV refractory patients with ETV administration.</p>

Construction and identification of siRNA eukaryotic expression vectors targeting on TGFβ1, TIMP-1 and TIMP-2 genes in vitro / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To construct the siRNA eukaryotic expression vectors targeting on TGFβ1, TIMP-1 and TIMP-2 and to investigate the inhibitory efficiency of target genes expression on rat hepatic stellate cell in vitro.</p><p><b>METHODS</b>The siRNA cDNA sequences of TGFβ1, TIMP-1 and TIMP-2 were designed, synthesized and inserted into plasmid pGenesil-1 respectively to generate eukaryotic expression plasmids. The plasmids were transfected into HSC T6 cells in vitro and the inhibitory efficiency of target genes expression was observed with real-time PCR and Western blot.</p><p><b>RESULTS</b>The eukaryotic expression vectors were constructed successfully. The expressions of TGFβ1 mRNA, TIMP-1 mRNA and TIMP-2mRNA in siRNA-transfected groups were decreased by 63.4% ± 8.0%, 64.5% ± 9.0% and 55.0% ± 17.0% respectively and the expressions of TGFβ1 protein, TIMP-1 protein and TIMP-2 protein were decreased by 57.8% ± 3.0%, 55.1% ± 5.0%, 49.3% ± 1.0% respectively as compared to the control groups.</p><p><b>CONCLUSIONS</b>The siRNA eukaryotic expression vectors constructed targeting on TGFβ1, TIMP-1 and TIMP-2 could reduce the expressions of target genes and they might be able to used for the exploration of new anti-fibrosis drugs genetically.</p>

Comparison of the efficacy of 48 week-Entecavir therapy with that of Adefovir therapy for chronic hepatitis B patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To compare the efficacy of 48 week-Entecavir therapy with that of Adefovir therapy for chronic hepatitis B patients.</p><p><b>METHODS</b>In this open-label study we randomly assigned 125 CHB patients to receive 0.5 mg of entecavir (n = 56) or 10mg of adefovir (n = 69) once daily for 48 weeks.</p><p><b>RESULTS</b>HBV DNA, ALT and HBeAg were quantified at baseline and at 0, 24, 48 weeks. At week 24 and 48, more patients in entecavir group than in adefovir group achieved undetectable serum HBV DNA level (68% vs 35%, 84% vs 49%, P < 0.05). The percentage of patients with normal ALT level in the two groups at week 48 was similar (100% vs 94%, P > 0.05). Among the HBeAg positive patients, more patients in entecavir group than in adefovir group had HBeAg loss at week 24 and 48 (23% vs 7%, 44% vs 15%, P < 0.05). The ratio of HBeAg seroconversion was similar in the two groups at week 24 (18% vs 7%, P > 0.05), but more patients in entecavir group than in adefovir group achieved HBeAg seroconversion at week 48 (33% vs 12%, P < 0.05). The retreated patients in the entecavir group had a higher chance to achieve undetectable serum HBV DNA level (79% vs 34%, P < 0.05), HBeAg loss (42% vs 17%, P > 0.05), and seroconversion (26% vs 17%, P > 0.05), than these in the adefovir group. The safety profiles and adverse event profiles were similar in the two groups.</p><p><b>CONCLUSIONS</b>Compared to adefovir, entecavir is more potent to suppress HBV replication.</p>

Analysis of spontaneous decline of HBV DNA in chronic hepatitis B patients in 12 weeks / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To analyze the spontaneous decline of HBV DNA in chronic hepatitis B patients in 12 weeks.</p><p><b>METHODS</b>Chronic hepatitis B patients not receiving antiviral treatment from 2003 to 2005 were divided into two groups according to the baseline value of ALT and TBil. Spontaneous decline of HBV DNA were retrospected, and the influence of the baseline value of ALT and TBil on spontaneous decline of HBV DNA was analyzed.</p><p><b>RESULTS</b>Total of 213 chronic hepatitis B patients (male 174, female 39, aged from 18 to 65) were recruited in this study, including 124 mild and moderate type of hepatitis B, 89 severe type of hepatitis B, and 19 patients (8.92%) were lost at the end of the 12th week. The mean baseline value of HBV DNA of all the patients was (6.66+/-1.03) log10 copies/ml, at 12 week the mean value of HBV DNA of all the patients was (5.98+/-1.53) log10 copies/ml (compared to baseline P<0.01), the decline value of HBV DNA was (0.68+/-1.46) log10 copies/ml. The mean baseline value of HBV DNA of patients with the severe type of hepatitis B was lower than that with the mild or moderate type of hepatitis B patients [(6.45+/-0.99) log10 copies/ml and (6.81+/-1.04) log10 copies/ml respectively] (P<0.05). However, there was no significant difference in the mean and the declined value of HBV DNA between these two groups at the 12th week (P<0.05). At the 12th week, the baseline values of ALT and TBil were higher in patients with HBV DNA<or=3 log10 copies/ml than those in patients with HBV DNA>3 log10 copies/ml (P>0.05); And there were no significant difference in the baseline values of ALT and TBil between patients with the declined value of HBV DNA>or=2 log10 copies/ml and patients with declined value of HBV DNA less than 2 log10 copies/ml. At the 12th week, the mean and the declined value of HBV DNA were similar between the patients with ALT<or=5xULN and the patients with ALT>5xULN at baseline. The mean baseline value of HBV DNA of patients in the group of patients whose baseline value of ALT<or=5xULN while TBil<or=5xULN was higher than that in the group of patients whose baseline value of ALT>5xULN while TBil>5xULN, ALT<or=5xULN while TBil>5xULN, ALT>5xULN while TBil<or=5xULN (P<0.05 respectively), there were no significant difference in the rate of the HBV DNA<or=3 log10 copies/ml and the rate of the declining value of HBV DNA<or=2 log10 copies/ml between the groups at 12 week (P>0.05 respectively).</p><p><b>CONCLUSIONS</b>There is spontaneous decline of HBV DNA in patients with chronic hepatitis B in 12 weeks, but the level of liver injury is not correlated with the level of spontaneous decline of HBV DNA in chronic hepatitis B patients in 12 weeks.</p>

Five years trial of entecavir for chronic hepatitis B patients failed with lamivudine therapy in the Chongqing area / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of five-year trail of entecavir for chronic hepatitis B patients failed with lamivudine therapy in the Chongqing area.</p><p><b>METHODS</b>32 patients failed with lamivudine therapy were enrolled in this study. In the double-blind phase, patients were randomly divided into entecavir 1.0 mg/d group (n = 28) and placebo group(n = 4) for 12 weeks. In the open-lable phase, patients received ETV 1.0 mg/d for 240 weeks. HBV DNA level, liver function, HBV serology were observed.</p><p><b>RESULTS</b>The mean reduction in HBV DNA level at week 12 was 4.05 log10 copies/ml in ETV group, and 0.08 log10 copies/ml in placebo group (P less than 0.05). The mean of HBV DNA level after 240 weeks of ETV treatment was decreased to 2.58 log10 copies/ml. The proportion of patients with HBV DNA less than 3 log10 copies/ml was 0, 6.25%, 15.6% , 50%, and 57.14% at 0, 8, 24, 96 and 240 weeks respectivfely. There were 2 patients with HBsAg seroconversion and 4 patients with HBeAg seroconversion at the end of the study. The ALT level returned to normal at week 12 and remained normal throughout the following 240 weeks. One patient had a severe adverse event during the trail.</p><p><b>CONCLUSION</b>Entecavir is effective and safe for the chronic hepatitis B patients failed with lamivudine therapy.</p>

Nucleos(t)ides as prophylaxis for the reactivation of hepatitis B virus in immunosuppressed patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the incidence of HBV reactivation and its clinical characteristics in the non-active HBsAg carriers receiving chemotherapy or immunosuppressant treatment, and to evaluate the role of nucleos(t)ide analogues against HBV reactivation.</p><p><b>METHODS</b>Non-active HBsAg carriers suffering from cancer, autoimmune diseases recieving immunosuppression therapy or cytotoxic chemotherapy were enrolled in the study. The in-patients from June 2002 to April 2007 in the Second Affiliated Hospital of Chongqing Medical University were assigned in the control group. The outpatients or in-patients with the similar disease condition from April 2007 to July 2008 were enrolled in the preventive group. The characteristics of HBV replication, liver damage, clinical symptoms and effectiveness of nucleos(t)ide analogues as prophylaxis for HBV reactivation were observed. The nucleos(t)ide analogues were used before chemotheraphy or immunosuppressive agents. The characheristics and clinical manifestations about HBV reactivation were investigated.</p><p><b>RESULTS</b>Of the 32 patients in preventive group, the amount of HBV DNA was detected in the 1rst, 3rd, 6th and 12th month after nucleos(t)ide analogues treatment. After chemotherapy or immunosuppressant treatment, only 9.4% (3/32) of them suffered from HBV reactivation, as indicated by positive HBV DNA in the serum and abnormal liver function. Ot the 77 patients in control group without nucleos(t)ide analogues treatment before chemotherapy or immunosuppression therapy, 58.4% (45/77) shown HBV reactivation, 4 patients in the control group died of liver failure, and one liver failure patient recieved liver transplantation.</p><p><b>CONCLUSION</b>HBV can be activated in immunosuppressed patients, nucleos(t)ide analogues should be used in early phase to prevent HBV reactivation.</p>

The effect of the different immunosuppression therapy on CD4(+)Foxp3(+) Treg cells in kidney recipients / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of the different immunosuppression therapy on CD4(+)Foxp3(+)regulatory T cells (CD4(+)Foxp3(+)Treg cells) in the peripheral blood monocytes of kidney transplantation recipients.</p><p><b>METHODS</b>A Closed Cohort study was conducted in 50 primary living kidney transplant recipients between January 2006 and January 2008, who had been followed up for 1 year. The recipients divided into calcineurin inhibitors group (CNI + MMF + Pred) (19 recipients, including cyclosporin group 10 recipients and tacrolimus group 9 recipients), rapamycin group (RAPA + MMF + Pred) (31 recipients). Twenty end-stage renal disease patients were in control group. The frequency of CD4(+)Foxp3(+)Treg cells in total CD4(+)T cells was analyzed by flow cytometry in peripheral blood from three groups, results were compared.</p><p><b>RESULTS</b>The clinical variables of recipients such as age, sex, cold ischemia time, human leucocyte antigen mismatch, panel reaction antibody, rejection episode were no significant difference. The percentage of CD4(+)Foxp3(+)Treg cells in total CD4(+) cells was significantly higher in rapamycin group and end-stage renal disease group than calcineurin inhibitors group (P < 0.01). The level of CD4(+)Foxp3(+)Treg cells between cyclosporin group and tacrolimus group was no significant difference (P > 0.05).</p><p><b>CONCLUSION</b>The level of CD4(+)Foxp3(+)Treg was significantly higher in patients receiving RAPA + MMF + Pred than the patients receiving CNI + MMF + Pred, which suggested that RAPA may be play a more important role in immune tolerance induction.</p>

A clinical study of N-acetylcysteine treatment in chronic hepatitis B patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of N-acetylcysteine (NAC) and glutathione (GSH) in treating chronic hepatitis B patients.</p><p><b>METHODS</b>Seventy-five patients with chronic hepatitis B were treated daily with an injection containing the same basic therapeutic drugs and randomly divided into a NAC group (50 patients) and a GSH group (25 patients). A daily dose of 8 grams of NAC and 1.2 grams of GSH was added to the injections of the two groups respectively. The trial lasted 28 days. Hepatic function and other biochemistry parameters (TBil, PTA, ALB et al) were tested on experimental day 0 and on days 7, 14, 21 and 28. The evaluation on the total effective rates of the NAC and GSH groups was based on the decreases of serum TBil and the increases of PTA.</p><p><b>RESULTS</b>Both NAC and GSH have therapeutic effects. The total effective rate was 84% in the NAC group and 72% in the GSH group. The rate of side effects was 13% in the NAC group.</p><p><b>CONCLUSION</b>NAC and GSH can decrease the level of serum TBil and increase PTA, but NAC was more effective in decreasing TBil than GSH. Serious adverse effects of NAC were not observed during the period of our treatment.</p>