Dual therapy with lopinavir/ritonavir plus lamivudine could be a viable alternative for antiretroviral-therapy-naive adults with HIV-1 infection regardless of HIV viral load or subgenotype in resource-limited settings: A randomised, open-label and non-inferiority study from China

Backgrounds: This randomised controlled, open-label, non-inferiority trial was conducted in antiretroviral-na飗e HIV-1-infected patients to assess the efficacy and safety of 48-week dual therapy of LPV/r plus 3TC (DT group) compared with Chinese first-line triple-therapy regimen (TT group). Methods: 198 were randomised to DT (n = 100) or TT (n = 98). Results: Ninety-two DT patients (92%) and 88 TT patients (89.8%) achieved HIV-1 RNA <50 copies/ml at week 48 (P = 0.629). Moreover, the safety profile was similar between two groups, and no secondary HIV resistance was observed. Conclusion: The results suggest that dual therapy of LPV/r plus 3TC is non-inferior to the first-line triple-therapy regimen in China.

ChIP-seq analysis of histone H3K9 trimethylation in peripheral blood mononuclear cells of membranous nephropathy patients

Membranous nephropathy (MN), characterized by the presence of diffuse thickening of the glomerular basement membrane and subepithelial in situ immune complex disposition, is the most common cause of idiopathic nephrotic syndrome in adults, with an incidence of 5-10 per million per year. A number of studies have confirmed the relevance of several experimental insights to the pathogenesis of human MN, but the specific biomarkers of MN have not been fully elucidated. As a result, our knowledge of the alterations in histone methylation in MN is unclear. We used chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) to analyze the variations in a methylated histone (H3K9me3) in peripheral blood mononuclear cells from 10 MN patients and 10 healthy subjects. There were 108 genes with significantly different expression in the MN patients compared with the normal controls. In MN patients, significantly increased activity was seen in 75 H3K9me3 genes, and decreased activity was seen in 33, compared with healthy subjects. Five positive genes, DiGeorge syndrome critical region gene 6 (DGCR6), sorting nexin 16 (SNX16), contactin 4 (CNTN4), baculoviral IAP repeat containing 3 (BIRC3), and baculoviral IAP repeat containing 2 (BIRC2), were selected and quantified. There were alterations of H3K9me3 in MN patients. These may be candidates to help explain pathogenesis in MN patients. Such novel findings show that H3K9me3 may be a potential biomarker or promising target for epigenetic-based MN therapies.

Experimental study on the atlanto-axial joint and related structures with regional anatomy and medical imaging / Estudio experimental de la articulación atlanto-axial y las estructuras relacionadas con la anatomía regional y la imagen médica

OBJECTIVE: To evaluate the anatomy and medical imaging characteristics in a study observing the atlanto-axial joint (AAJ) and related structures. METHODS: Eight cadaveric specimens of the AAJ segment were studied with both anatomical and imaging methods. The vertebral arteries of the AAJ segment (VA-A), the first and second cervical nerves (CN1, CN2) and synovial fold (SF) of the AAJ were observed and measured. RESULT: After extending from the vertebral canal, the CN1 goes between the posterior arch of the atlas and VA-A, and the CN2 passes between the posterior arch of the atlas and axis, and is posterior to VA-A. Among the eight cases, six were found in the SF in the central anterior AAJ and five in lateral. The vertebral arteries of the AAJ segment go along the AAJ with four curves, of which the second and fourth are away from the bone structure of the AAJ. The distance from CN1, CN2 to VA-A and that from the second, fourth curve of VA-A to AAJ is 0.0-2.2 mm, 0.0-3.6 mm and 0.0-4.8 mm, 2.0-7.9 mm respectively. There is no significant difference between the measurements made anatomically and those by the imaging method (p > 0.05). CONCLUSION: The anatomical method has advantages in observing the CN and SF, while the imaging method shows clearly and directly the VA-A and AAJ. Both are mutually complementary with consistent measurements. The combined use of the two provides a new way to study the complicated anatomy in this region.

OBJETIVO: Evaluar las características del método anatómico y el uso de la imagen médica en un estudio de observación de la articulación atlanto-axial (AAA) y estructuras relacionadas. MÉTODOS: Se estudiaron ocho especimenes cadavéricos del segmento de la AAA tanto con métodos anatómicos como con métodos de imaginología médica. Las arterias vertebrales del segmento de AAA (AV-A), el primer y el segundo nervios cervicales (NC1, NC2) y los pliegues sinoviales (PS) fueron observados y medidos. RESULTADO: Tras de extenderse desde el canal vertebral, el NC1 se extiende entre el arco posterior del atlas, y el NC2 pasa entre el arco posterior del atlas y el axis, y es posterior a las AV-A. Entre los ocho casos, se encontraron seis en los PS en la AAA anterior central, y cinco en la lateral. Las arterias vertebrales del segmento AAA van junto con la AAA con cuatro curvas, de las cuales la segunda y la cuarta están separadas de la estructura ósea de la AAA. La distancia del NC1 y NC2, a las AV-A, y la de la segunda y cuarta curvas de las AV-A a la AAA es 0.0-2.2 mm, 0.0-3.6 mm y 0.0-4.8 mm, 2.0-7.9 mm respectivamente. No hay ninguna diferencia significativa entre las mediciones realizadas anatómicamente y las hechas mediante métodos de imaginología (p > 0.05). CONCLUSIÓN: El método anatómico tiene ventajas al observar el NC y los PS, mientras que el método imaginológico muestra clara y directamente las AV-A y la AAA. Ambos son mutualmente complementarios con las mediciones. El uso combinado de los dos proporciona una nueva manera de estudiar la complicada anatomía de esta región.

Thy-1 functions as a recognition/signaling molecule during mouse T lymphocyte development

Thy-1 is a prototype of mammalian glycosilphosphatidylinositol(GPI)-anchored molecules and belongs to the Ig sperfamily. This cell surface glycoprotein is expressed on mouse T lymphocytes, neurons and hematopoietic stem cells. Despite detailed structural studies, little is known about the physiological role(s) of Thy-1. We discuss here our results on the of Thy-1 in immature T lymphocytes during intrathymic maturation. It was observed that Thy-1-mediated adhesion of mouse thymocytes to thymic stromal cells occurs through interaction with an unknown ligand. The interaction occurs by a Ca²+ -independent mechanism and does not require TCR/CD3 surface expression. To evaluate the signal transduction upon Thy-1 ligation in immature thymocytes, we cultured mouse thymocytes with monoclonal antibodies specific for Thy-1, immobilized onto the tissue culture plates. Monoclonal antibodies directed at determinants located in a defined epitope domain, but not others, triggered marked physiological cell death (apoptosis) of immature thymocytes, as evidenced by morphological and biochemical data. This apoptosis is independent of the cell surface expression of TCR/CD3. It is a developmentally regulated process since the period in which thymocytes are sensitive to Thy-1-dependent apoptosis corresponds to the developmental "window" during which massive death of immature thymocytes takes place within the thymus. Therefore, we propose that Thy-1 could function as a cell survival/death regulator in mouse T lymphocyte development