Objective To investigate the efficacy and safety of adefovir dipivoxil(ADV)for chronic hepatitis B(CHB)patients with lamivudine(LMD)resistance.MethodsA total of 247 LMDresistant CHB patients were included in this multi-center,randomized(1:1),double-blinded and LMDcontrolled clinical trial.All subjects were swithed to open-labelled ADV treatment after 12-week doubleblinded stage.Serum HBV DNA and ALT levels were monitored and safety assessments were conducted at 12th and 48th week during the treatment.Results At 12th week.mean reduction of ALT in trial group was 35.9 U/L,and the reduction of HBV DNA was 3.01 log10 copies/mL.The reductions of HBV DNA in 61.8%(76/123)subjects were more than 2 log10 copies/mL.While in the control group,ALT raised 2.8 U/L in average,and the reduction of HBV DNA was 0.78 log10 copies/mL.The reductions of HBV DNA in 17.7%(22/124)subjects were more than 2 log10 copies/mL.At 48th week,mean reduction of ALT in trial group was 59.7 U/L,and the reduction of HBV DNA was 4.70 log10 copies/mL.The reductions of HBV DNA in 87.0%(107/123)subjects were more than 2 log10 copies/mL.While in the control group,mean reduclion of ALT was 56.6 U/L,and the reduction of HBV DNA was 4.43 log10 eopies/mL.The reductions of HBV DNA in 85.5%(106/124)subjects were more than 2 log10 copies/mL.No severe adverse effect related to the investigational product was observed in both groups.Conclusion ADV is safe and effective in the treatment of LMD-resistant CHB patients with virological and biochemical improvements.

Objective To investigate the screening and evaluating methods of positive recombinant clones for small fragments such as LoxP sequence. Methods Synthesized LoxP and vector complementary sequence were used as the upper and lower primer respectively, and colonies were used directly as the templates of polymerase chain reaction (PCR). The presence of 784 bp strap in electrophoresis was seen as positive. The positive recombinant clones screened by PCR were evaluated contrastively by restriction endonuclease digestion and verified by DNA sequence analysis. Results Among the six colonies randomly screened by PCR, three showed positive straps and one was verified by DNA sequence analysis. However, the electrophoresis only showed unclear and clouding straps when the three positive recombinant clones were evaluated by restriction endonuclease digestion. Conclusion Self-primer colony PCR is a high-speed, convenient, economic and effective method for screening and evaluating of positive clones recombinated by small fragments such as LoxP sequence.

Objective To investigate the efficacy and mechanism of compound glycyrrhizin on patients with serious hepatitis. Methods Thirty patients who were hospitalized from August 2005 to June 2007 with diagnosed with serious hepatitis were enrolled into treatment group and treated by compound glycyrrhizin injection ( 80 to 100 ml per day,for 3 consecutive weeks) and common supporting medicines,while the other 30 patients in control group were treated only with same supporting medicines. Mortality,biochemical parameters, plasma levels of endotoxin and inflammatory factors in patients of both groups were observed during the treatment. Results By the end of three-week of treatment,8 patients in the treatment group died with the mortality of 26. 7% ( 8 /30) . Thirteen patients died in the control group and the mortality was 43. 3% ( 13 /30) . Serum ALT and AST levels in treatment group were significantly lower than those of control group during the treatment. The average level of serum total bilirubin and plasma prothrombin time in treatment group was lower than those of control group by end of the third treatment week. The level of TNF-alpha in treatment group was lower than that of control group during treatment. The levels of plasma endotoxin and interleukin-6 in treatment group were significantly lower than those of the control group at the second and third treatment week. Conclusion Compound glycyrrhizin improves the biochemical parameters of patients with serious hepatitis,and probably,improves the survival of patients with severe hepatitis. The implying mechanism might be that compound glycyrrhizin declines plasma endotoxin levels and lessen cytokine-induced secondary hepatic injuries.

Objective To investigate primary anti-tuberculosis drug resistance in patients with acquired immunodeficiency syndrome (AIDS) and tuberculosis in Chongqing area.Methods Clinical data of 119 patients with AIDS and tuberculosis were retrospectively collected.Anti-tuberculosis drug resistance rates were analyzed according to drug susceptibility testing, and their correlations with CD4+ T lymphocytes counts, initially treatment or retreatment and clinical forms of tuberculosis were also analyzed.Comparison between groups was analyzed by x2 test.Results Thirty-eight patients (31.9%) showed anti-tuberculosis drug resistance among the 119 patients with completed results of drug susceptibility testing results.The percentages of mono-resistance, poly-resistance, multi-drug resistance (MDR) and extensive drug resistance (XDR) were 11.7%, 7.6%, 6.7% and 5.9%, respectively.The resistance rate of isoniazid (22.7%, 28/119) was the highest among first-line anti-tuberculosis drugs and that of pasiniazide (11.0%, 14/119) was the highest among second-line drugs.Drug resistance rates among patients with different levels of CD4+ T lymphocytes counts did not differ significantly (the cut-off of CD4+ T lymphocytes count was 50/μL: x2=0.545, P=0.461;cut-off value was 100/μL: x2=0.652, P=0.420).Patents with milliary pulmonary tuberculosis had a significantly higher drug resistance rate (64.0%) than those with secondary pulmonary tuberculosis (27.6%).Conclusions The prevalence of anti-tuberculosis drug resistance prior to anti-tuberculosis treatment initiation is high among AIDS patients with tuberculosis in Chongqing area.Patients with milliary pulmonary tuberculosis tend to have higher anti-tuberculosis drug resistance, but drug resistance does not appear to correlate with CD4+ T lymphocytes counts.

Cytomegalovirus retinitis (CMVR) is the most frequently encountered ocular opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS). In the absence of accurate diagnosis and effective treatment, CMVR can cause different degree of ocular injury and even blindness in AIDS patients. Therefore, the early diagnosis and timely treatment of CMVR is particularly important. This article aims to review the progress in research on the clinical manifestations, diagnosis and treatment drugs of CMVR.

Hepatocytes ; pathology ; Humans ; Liver Diseases ; pathology ; Stem Cells ; pathology

The key materials for bioartificial liver (BAL) construction include biomaterials and scaffolding materials. The former mainly refers to hepatocytes, nonparenchymal cells, etc. The latter mainly refers to films and other scaffolding materials, the properties of which correlate directly with hepatocyte growth and functions, and thus are related to the support effects of BAL. Several kinds of scaffolding materials frequently used for BAL construction in recent years are reviewed in this article.
Biocompatible Materials ; Liver, Artificial ; Membranes, Artificial ; Polyurethanes ; Polyvinyls ; Tissue Engineering

Objective:To investigate the influence of hepatitis B virus (HBV) combined with human immunodeficiency virus (HIV) infection on the efficacy of anti-retroviral therapy (ART).Methods:The data of 269 HIV-infected patients treated in Chongqing Public Health Medical Center from September 2016 to October 2019 were collected. The patients were divided into HIV monoinfection group and HIV/HBV coinfection group. The changes in liver function, CD4 + T lymphocyte count, and HIV RNA level between the two groups were compared when ART started and at different time points (2, 4, 8, 12, 24, 36, 48, and 96 weeks) after ART started. Statistical analysis were performed by independent sample t test, rank sum test and chi-square test. Results:A total of 145 patients with HIV monoinfection and 124 patients with HIV/HBV coinfection were collected. There were no statistically significant differences in liver function indexes (aspartate aminotransferase ( t=9.566), alanine aminotransferase ( t=-4.652) and total bilirubin ( t=-25.476)) between the two groups of patients when ART started (all P>0.05). At 24, 48 and 96 weeks after ART, the CD4 + T lymphocyte counts in the HIV monoinfection group and the HIV/HBV coinfection group were (305.9±156.9)/μL vs (266.2±172.5)/μL, (388.5±226.1)/μL vs (380.8±287.4)/μL and (369.5±191.4)/μL vs (453.6±179.6)/μL, respectively. At 48, 72 and 96 weeks after ART, the CD4 + T lymphocyte count increasing values were 121.0(-52.5, 144.5)/μL vs 156.0(-35.8, 185.8)/μL, 139.0(-116.0, 176.8)/μL vs 114.5(-59.5, 229.0)/μL and -91.0(-110.0, 153.3)/μL vs -94.0(-130.8, 114.3)/μL, respectively. The differences were all not statistically significant ( t=-0.516, -0.066 and -1.414, Z=-1.715、-0.802 and -1.602, respectively, all P>0.05). At 24, 48, and 96 weeks after ART, the HIV RNA inhibition rates in the HIV monoinfection group were 89.7%(130/145), 96.6%(140/145), and 96.6%(140/145), respectively, and those in the HIV/HBV coinfection group were 87.1%(108/124), 92.7%(115/124) and 94.4%(117/124), respectively. The differences were all not statistically significant ( χ2=0.026, 0.053 and 0.017, respectively, all P>0.05). In the second and fourth weeks after ART, the abnormal liver function rates of the HIV monoinfection group were 3.4%(5/145) and 6.2%(9/145), respectively, which were lower than those in the HIV/HBV coinfection group (21.0%(26/124) and 13.7%(17/124), respectively). The differences were both statistically significant ( χ2=20.121 and 4.309, respectively, both P<0.05). However, the abnormal liver function rates in the two group in the 8th week after ART were 10.3%(15/145) and 9.7%(12/124), respectively, and those in the 12th week were 9.0%(13/145) and 9.7%(12/124), respectively, and those in the 24th week were 9.7%(14/145) and 8.9%(11/124), respectively, and those in the 36th week were 9.7%(14/145) and 10.5%(13/124), respectively, and those in the 48th week were 8.3%(12/145) and 8.1%(10/124), respectively, and those in the 96th week were 2.8%(4/145) and 0(0/124), respectively. The differences were all not statistically significant ( χ2=0.330, 0.040, 0.049, 0.051, 0.004 and 3.472, respectively, all P>0.05). Conclusion:HBV coinfection has no adverse effect on the ART effect of HIV-infected patients.

Incomplete immune reconstitution remains a global challenge for human immunodeficiency virus (HIV) treatment in the present era of potent antiretroviral therapy (ART), especially for those individuals referred to as immunological non-responders (INRs), who exhibit dramatically low CD4 + T-cell counts despite the use of effective antiretroviral therapy, with long-term inhibition of viral replication. In this review, we provide a critical overview of the concept of ART-treated HIV-positive immunological non-response, and also explain the known mechanisms which could potentially account for the emergence of immunological non-response in some HIV-infected individuals treated with appropriate and effective ART. We found that immune cell exhaustion, combined with chronic inflammation and the HIV-associated dysbiosis syndrome, may represent strategic aspects of the immune response that may be fundamental to incomplete immune recovery. Interestingly, we noted from the literature that metformin exhibits properties and characteristics that may potentially be useful to specifically target immune cell exhaustion, chronic inflammation, and HIV-associated gut dysbiosis syndrome, mechanisms which are now recognized for their critically important complicity in HIV disease-related incomplete immune recovery. In light of evidence discussed in this review, it can be seen that metformin may be of particularly favorable use if utilized as adjunctive treatment in INRs to potentially enhance immune reconstitution. The approach described herein may represent a promising area of therapeutic intervention, aiding in significantly reducing the risk of HIV disease progression and mortality in a particularly vulnerable subgroup of HIV-positive individuals.
Humans ; Immune Reconstitution ; CD4 Lymphocyte Count ; Metformin/therapeutic use* ; Dysbiosis ; Antiretroviral Therapy, Highly Active ; HIV Infections/drug therapy* ; CD4-Positive T-Lymphocytes ; HIV ; Syndrome

OBJECTIVETo establish a rat model for hepatic oval cell proliferation and to observe the relationship between 2-acetaminofluorene (AAF) dosage and oval cell proliferation in the rat liver.

METHODSMale Wistar rats weighing 150 g received daily oral gavage of AAF for 4 days before operation and up to 7 days after operation. Two-thirds hepatectomy was performed on the 5th day and the gavage was not performed on the day of operation. AFF was given with the dosage of 2.5 mg/kg, 5 mg/kg, 10 mg/kg, 15 mg/kg, and 20 mg/kg body weight. Animals in control group were given saline. Three rats from each group were killed every 2~3 days after hepatectomy and liver slices were fixed and processed for routine histology and immunohistochemistry.

RESULTSHepatic oval cells were not observed in the liver of controls and only a few were detected in the liver of 2.5 mg/kg and 5 mg/kg groups. However, obvious oval cell proliferation was seen in the liver of 10 mg/kg, 15 mg/kg, and 20 mg/kg groups. Hepatic oval cells were stained positive for cytokeratin 19, OV6, vimentin and proliferating cell nuclear antigen (PCNA).

CONCLUSIONSSatisfactory rat models for hepatic oval cell proliferation can be obtained using our scheme when AAF is dosed at 10~20 mg/kg body weight.

Animals ; Cell Division ; physiology ; Cells, Cultured ; Culture Media ; Immunohistochemistry ; Liver ; cytology ; Male ; Models, Animal ; Rats ; Rats, Wistar ; Stem Cells ; physiology