Efficacy and safety of the long-acting fusion inhibitor albuvirtide in antiretroviral-experienced adults with human immunodeficiency virus-1: interim analysis of the randomized, controlled, phase 3, non-inferiority TALENT study / 中华医学杂志(英文版)

BACKGROUND@#Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs.@*METHODS@#We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%.@*RESULTS@#At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group.@*CONCLUSIONS@#The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure.@*TRIAL REGISTRATION@#ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx.

Study on environmental and psychological risk factors for female infertility / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the environmental and psychological risk factors for female infertility and to provide a scientific basis for the prevention and control of female infertility.</p><p><b>METHODS</b>In a hospital-based case-control study, a self-designed questionnaire was used to survey the cases and controls (1:1) with nation and age (± 2 years) as matching variables. Univariate and multivariate conditional logistic regression models were employed to analyze the datasets.</p><p><b>RESULTS</b>The univariate analysis showed that female infertility was related to the following factors: eating fried foods, alcohol consumption, smoking, staying up late, perm, housing decoration, contact with heavy metals, exposure to radiation, contact with pesticides, working in hot environment, mental stress, uneasiness, helplessness, and despair. The multivariate analysis showed that staying up late (OR = 2.937), housing decoration (OR = 2.963), exposure to radiation (OR = 2.506), contact with pesticides (OR = 2.908), and mental stress (OR = 4.101) were the main risk factors for female infertility. Furthermore, there was an interaction between staying up late and mental stress.</p><p><b>CONCLUSION</b>Female infertility is caused by multiple factors including staying up late, housing decoration, exposure to radiation, contact with pesticides, and mental stress, and there is an interaction between staying up late and mental stress.</p>

Effects of anisodamine on the expressions of vascular endothelial growth factor and intercellular adhesion molecule 1 in experimental infusion phlebitis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Infusion phlebitis is the most common side effect of clinical intravenous drug therapy and several clinical studies have demonstrated that anisodamine can effectively prevent the occurrence of infusion phlebitis. This study was designed to investigate effects of anisodamine on the expressions of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM-1) in a rabbit model of infusion phlebitis and to analyze the mechanisms of anisodamine effect on the prevention and treatment of experimental infusion phlebitis.</p><p><b>METHODS</b>Twenty-four specific pathogen-free male Japanese white rabbits were randomly assigned to the control group, the model group, the magnesium sulfate group and the anisodamine group. The rabbit model of infusion phlebitis, induced by intravenous administration, was established and expressions of VEGF and ICAM-1 were determined and contrasted with the control group treated with normal saline. We evaluated expression by histopathology, immunohistochemistry, reverse transcription-polymerase chain reaction, and Western blotting assay.</p><p><b>RESULTS</b>Pathohistological changes of the model group were observed, such as loss of venous endothelial cells, inflammatory cell infiltration, edema and thrombus. The magnesium sulfate group and the anisodamine group showed significant protective effects on vascular congestion, inflammatory cell infiltration, proliferation, swelling of endothelium and perivascular hemorrhage. The model group showed the highest expressions of VEGF and ICAM-1 of the four groups (P < 0.01). On the contrary, anisodamine alleviated the inflammatory damage by significantly reducing the expressions of VEGF and ICAM-1 compared with the model group (P < 0.01). There was no significant difference in the expressions of VEGF and ICAM-1 between the magnesium sulfate group and the anisodamine group (P > 0.05).</p><p><b>CONCLUSION</b>Anisodamine alleviates inflammatory damage by significantly reducing the expressions of VEGF and ICAM-1, and shows significant protective effects in an animal model of infusion phlebitis.</p>

Magnetic resonance spectroscopy in the diagnosis of cognitive impairment in AIDS patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The pathological abnormalities of the AIDS patients lie in the subcortical regions of the brain, specifically the deep white matter and basal ganglia, while the extent of pathology generally correlates with the severity of cognitive impairments in the white matter and basal ganglia. Brain metabolite changes of these lesions can reflect the pathological abnormalities. The purpose of this study was to assess the value of magnetic resonance spectroscopy (MRS) in the diagnosis of cognitive impairment in AIDS patients.</p><p><b>METHODS</b>3.0T MR was used to measure N-acetyl aspartate (NAA), choline (Cho), myo-inositol (MI) and creatinine (Cr) in the frontal white matter, basal ganglia and parietal cortex of 21 AIDS patients with dementia complex (ADC), 19 AIDS patients with neuroasymptomatic (NAS) and 20 seronegative (SN) controls. Then we compared the difference of metabolic rate between AIDS patients and SN groups.</p><p><b>RESULTS</b>NAA/Cr (mean = 1.2502, SD = 0.1600) was significantly decreased and Cho/Cr (mean = 1.2028, SD = 1.1655) was increased in the frontal white matter in ADC group, while NAA/Cr (mean = 1.5334, SD = 0.0513) was reduced in NAS group when compared with SN group. NAA/Cr in the basal ganglia was decreased in both ADC and NAS groups (mean = 1.2625, SD = 0.1615 and mean = 1.5278, SD = 0.0380, respectively). Cho/Cr (mean = 1.1631, SD = 0.0981) was markedly increased in ADC group. Although NAA/Cr, Cho/Cr and MI/Cr in the parietal cortex had a certain change in both ADC and NAS groups compared with SN group, the differences were not statistically significant.</p><p><b>CONCLUSIONS</b>The brain metabolite changes of AIDS patients are correlated with cognitive impairments. MRS can be used as a valuable inspection method to assess cognitive impairments in AIDS patients.</p>

Abeta(25-35) and ginsenoside Rb1 influence on the expression of GSK-3beta, CDK-5 and PP2A in differentiated neural stem cells of rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the expression of GSK-3beta, CDK-5 and PP2A and the regulation of them by Abeta(25-35) and ginsenoside Rb1 after neural stem cells (NSCs) are transformed into neurons.</p><p><b>METHODS</b>To culture NSCs from the dentate gyrus of newborn rats(24 h) hippocampus in vitro. NSCs of the third passage were induced towards neurons; the expressions of GSK-3beta(pTyr279,216), PP2A and the regulation of them by Abeta(25-35) and ginsenoside Rb1 were tested by the immunofluorescence cytochemical staining after NSCs had been induced for one week; The expressions of GSK-3beta, CDK-5, PP2A and the regulation of them by Abeta(25-35) and ginsenoside Rb1 were detected with RT-PCR.</p><p><b>RESULTS</b>Immunofluorescence cytochemisty showed that neural cells from NSCs which had been differentiated after one week could express GSK-3j (pTyr279,216)and PP2A. Abeta(25-35) could enhance the expression of GSK-3beta(pTyr279,216), meanwhile it also restrained the expression of PP2A. Moreover ginsenoside Rb1 could reverse the affect of Abeta(25-35). RT-PCR found that neural stem cells which had been differentiated after one week could express GSK-3beta, CDK-5, PP2A . The expression of GSK-3beta and CDK-5 rose up and the expression of PP2A weakened when they were treated by Abeta(25-35). However, the effect of Abeta(25-35) was restrained when they were pretreated by ginsenoside Rb1.</p><p><b>CONCLUSION</b>These observations indicated that NSCs which were cultured and induced in vitro can express GSK-3beta, CDK-5 and PP2A; moreover Abeta(25-35) and ginsenoside Rb1 can regulate the expressions of GSK-3beta, CDK-5 and PP2A. It hints that cells which differentiated from neural stem cells in vitro have protein phosphorylation regulation system of normal cells.</p>

Characteristics of HIV-1-specific CD8 T-cell responses and their role in loss of viremia in children chronically infected with HIV-1 undergoing highly active antiretroviral therapy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Few studies have examined the properties of human immunodeficiency virus type 1 (HIV-1) epitope-specific cytotoxic T lymphocyte (CTL) responses in children. To address this issue, we characterized epitope-specific CTL responses and analyzed the determinants that may affect CTL responses before and after highly active antiretroviral therapy (HAART) in children with HIV-1 infection.</p><p><b>METHODS</b>A total of 22 HIV-1-infected children and 23 uninfected healthy children as control were enrolled in the study. Circulating CD4 T cells and HIV-1 RNA load in plasma were routinely measured. Peripheral HIV-1-specific CTL frequency and HIV-1 epitope-specific, interferon-gamma (IFN-gamma)-producing T lymphocytes were measured using tetramer staining and enzyme-linked immunospot (ELISPOT) assay, respectively. Circulating dendritic cell (DC) subsets were monitored with FACS analysis.</p><p><b>RESULTS</b>More than 80% of the children with HIV-1 infection exhibited a positive HIV-1-epitope-specific CTL response at baseline, but HIV-specific CTLs and IFN-gamma-producing lymphocytes decreased in patients who responded to HAART in comparison with non-responders and HAART-naive children. The duration of virus suppression resulted from HAART was inversely correlated with CTL frequency. While in HAART-naive children, HIV-1-specific CTL frequency was positively correlated with myeloid DC (mDC) frequency, although the cause and effect relationship between the DCs and CTLs remains unknown.</p><p><b>CONCLUSIONS</b>HIV-1-epitope-specific CTL responses are dependent on antigenic stimulation. The impaired DC subsets in blood might result in a defect in DC-mediated T cell responses. These findings may provide insight into understanding the factors and related mechanisms that influence the outcome of HIV-1 carriers to HAART or future antiviral therapies.</p>

Coinfection with HBV and HCV in 128 AIDS patients infected through blood transmission / 中国医学科学院学报

<p><b>OBJECTIVE</b>To analyze the clinical features of 128 acquired immunodeficiency syndrome (AIDS) patients infected through blood transmission who were coinfected with hepatitis B virus (HBV) and hepatitis C virus (HCV).</p><p><b>METHODS</b>The prevalence, liver functions, and some immunological profiles of 128 AIDS patients coinfected with HBV and HCV were retrospectively analyzed.</p><p><b>RESULTS</b>Among the 128 AIDS patients, 107 (83.6%) were coinfected with HCV, among which 40 (31.3%) patients had abnormal liver functions or liver damage and 15 (11.7%) patients experienced hepatitis symptoms. Three (2.3%) AIDS patients were singly coinfected with HBV, and all of them had abnormal liver functions and hepatitis symptoms. Seven (5.5%) patients were coinfected with HIV/HCV/HBV and none of them had abnormal liver functions or hepatitis symptoms. Eleven (8.6%) patients were only infected with HIV.</p><p><b>CONCLUSIONS</b>The prevalence of blood-transmitted HIV patients coinfected with HCV is higher than with HBV. The clinical outcomes of HIV coinfection with HCV and HBV are different.</p>