RESUMEN
BACKGROUND: Overexpression of PTK7 has been found in multiple cancers and has been proposed to serve as a prognostic marker for intrahepatic cholangiocarcinoma. Its role in esophageal cancer, however, remains to be clarified. We hypothesize that PTK7 positively regulates tumorigenesis of esophageal cancer. METHODS: We examined PTK7 expression pattern in human esophageal squamous carcinoma by Oncomine expression analysis and by immunohistochemistry (IHC) staining. We knocked down PTK7 in two esophageal squamous cell carcinoma cell lines, TE-5, and TE-9, by siRNA, and evaluated cell proliferation, apoptosis, and migration ofPTK7-defective cells. Expressions of major apoptotic regulators and effectors were also determined by quantitative real-time PCR in PTK7-defective cells. We further overexpressed PTK7 in the cell to evaluate its effects on cell proliferation, apoptosis, and migration. RESULTS: Both Oncomine expression and IHC analyses showed that PTK7 is overexpressed in clinical esophageal squamous cell carcinoma tumors. PTK7 siRNA suppressed cell growth and promoted apoptosis of TE-5 and TE-9. PTK7-defective cells further displayed reduced cellular migration that was concomitant with upregulation of E-cadherin. Conversely, overexpression of PTK7 promotes cell proliferation and invasion, while apoptosis of the PTK7-overexpressing cells is repressed. Notably, major apoptotic regulators, such as p53 and caspases, are significantly upregulated in siPTK7 cells. CONCLUSIONS: PTK7 plays an oncogenic role in tumorigenesis and metastasis of esophageal squamous carcinoma. PTK7 achieves its oncogenic function in esophageal squamous cell carcinoma partially through the negative regulation of apoptosis.
Asunto(s)
Carcinoma de Células Escamosas/patología , Moléculas de Adhesión Celular/metabolismo , Movimiento Celular , Proliferación Celular , Neoplasias Esofágicas/patología , Proteínas Tirosina Quinasas Receptoras/metabolismo , Apoptosis , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Moléculas de Adhesión Celular/genética , Ciclo Celular , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Proteínas Tirosina Quinasas Receptoras/genética , Células Tumorales CultivadasRESUMEN
Late stent thrombosis (LST) following drug-eluting stent (DES) implantation in patients with coronary artery disease (CAD) is often associated with delayed vascular healing, resulting from vascular inflammation and hypersensitivity to durable polymers and drugs. Therefore, DES design, materials, and coatings have been technologically revolutionized. Herein, we designed a novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent (AGF-BP-SES), with a sirolimus content of only about one-third of traditional DES. The mechanical performances of AGF-BP-SES during compression and expansion were investigated. The pharmacokinetic (PK) profile of sirolimus was studied in the swine model. The in vivo efficacy of AGF-BP-SES was compared with that of Xience PRIME® stent. The results showed that AGF-BP-SES exhibited mechanical properties similar to traditional DES, including the rebound ratio of radial contraction/direction, rebound ratio of axial contraction/direction, and inhomogeneity of compression/expansion. Despite utilizing a reduced dose of sirolimus, AGF-BP-SES delivered sirolimus to the coronary artery in a controlled and efficient manner. The stent maintained a safe and effective local drug concentration without local or systemic risks. In the swine model, histopathological indicators predicted safety and biocompatibility of AGF-BP-SES. In conclusion, AGF-BP-SES maintained similar mechanical properties as other stents while reducing the drug-loading capacity, and showed a favorable safety and efficacy profile of the targeted DES.
Asunto(s)
Materiales Biocompatibles/química , Sistemas de Liberación de Medicamentos , Stents Liberadores de Fármacos , Polímeros/química , Sirolimus/farmacocinética , Implantes Absorbibles , Animales , Área Bajo la Curva , Enfermedad de la Arteria Coronaria/terapia , Vasos Coronarios/efectos de los fármacos , Vasos Coronarios/patología , Análisis de Elementos Finitos , Humanos , Microscopía Electrónica de Rastreo , Seguridad del Paciente , Sirolimus/administración & dosificación , Stents , Porcinos , TrombosisRESUMEN
BACKGROUND: The aim of this study was to describe 3-year mortality rates, associated risk factors, and long-term clinical outcomes of children enrolled in China's national free pediatric antiretroviral therapy (ART) program. METHODS: Records were abstracted from the national human immunodeficiency virus (HIV)/AIDS case reporting and national pediatric ART databases for all HIV-positive children ≤15 years old who initiated ART prior to December 2010. Mortality risk factors over 3 years of follow-up were examined using Cox proportional hazards regression models. Life tables were used to determine survival rate over time. Longitudinal plots of CD4(+) T-cell percentage (CD4%), hemoglobin level, weight-for-age z (WAZ) score, and height-for-age z (HAZ) score were created using generalized estimating equation models. RESULTS: Among the 1818 children included in our cohort, 93 deaths were recorded in 4022 child-years (CY) of observed time for an overall mortality rate of 2.31 per 100 CY (95% confidence interval [CI], 1.75-2.78). The strongest factor associated with mortality was baseline WAZ score <-2 (adjusted hazard ratio [HR] = 9.1; 95% CI, 2.5-33.2), followed by World Health Organization stage III or IV disease (adjusted HR = 2.4; 95% CI, 1.1-5.2), and hemoglobin <90 g/L (adjusted HR = 2.2; 95% CI, 1.2-3.9). CD4%, hemoglobin level, WAZ score, and HAZ score increased over time. CONCLUSIONS: Our finding that 94% of children engaged in this program are still alive and of improved health after 3 years of treatment demonstrates that China's national pediatric ART program is effective. This program needs to be expanded to better meet treatment demands, and efforts to identify HIV-positive children earlier must be prioritized.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa/métodos , Infecciones por VIH/mortalidad , Adolescente , Niño , Preescolar , China , Estudios de Cohortes , Infecciones por VIH/tratamiento farmacológico , Humanos , Lactante , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVES: To identify factors influencing mortality in an HIV programme providing care to large numbers of injecting drug users (IDUs) and patients co-infected with hepatitis C (HCV). METHODS: A longitudinal analysis of monitoring data from HIV-infected adults who started antiretroviral therapy (ART) between 2003 and 2009 was performed. Mortality and programme attrition rates within 2 years of ART initiation were estimated. Associations with individual-level factors were assessed with multivariable Cox and piece-wise Cox regression. RESULTS: A total of 1671 person-years of follow-up from 1014 individuals was analysed. Thirty-four percent of patients were women and 33% were current or ex-IDUs. 36.2% of patients (90.8% of IDUs) were co-infected with HCV. Two-year all-cause mortality rate was 5.4 per 100 person-years (95% CI, 4.4-6.7). Most HIV-related deaths occurred within 6 months of ART start (36, 67.9%), but only 5 (25.0%) non-HIV-related deaths were recorded during this period. Mortality was higher in older patients (HR = 2.50; 95% CI, 1.42-4.40 for ≥40 compared to 15-29 years), and in those with initial BMI < 18.5 kg/m(2) (HR = 3.38; 95% CI, 1.82-5.32), poor adherence to treatment (HR = 5.13; 95% CI, 2.47-10.65 during the second year of therapy), or low initial CD4 cell count (HR = 4.55; 95% CI, 1.54-13.41 for <100 compared to ≥100 cells/µl). Risk of death was not associated with IDU status (P = 0.38). CONCLUSION: Increased mortality was associated with late presentation of patients. In this programme, death rates were similar regardless of injection drug exposure, supporting the notion that satisfactory treatment outcomes can be achieved when comprehensive care is provided to these patients.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Causas de Muerte , Consumidores de Drogas , Infecciones por VIH/mortalidad , Hepatitis C/complicaciones , Abuso de Sustancias por Vía Intravenosa/complicaciones , Adulto , Factores de Edad , Índice de Masa Corporal , Recuento de Linfocito CD4 , Atención a la Salud , Femenino , Estudios de Seguimiento , VIH , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Hepacivirus , Hepatitis C/tratamiento farmacológico , Hepatitis C/virología , Humanos , Incidencia , Estudios Longitudinales , Masculino , Cooperación del Paciente , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
In 2003, the Chinese Government initiated a free antiretroviral therapy (ART) program focusing on adult AIDS patients. Pediatric antiretroviral (ARV) formulations were yet unavailable. It was not until July 2005, with the initiation of a two-stage program implemented by the Chinese Ministry of Health, that pediatric formulations became accessible in China. Initially, the pediatric ART program was piloted in six provinces with the highest incidences of pediatric HIV/AIDS. The pilot stage allowed the Chinese Center for Disease Control and Prevention (CCDC) to finalize entry criteria, treatment regimen, and patient monitoring and follow-up procedures. The second stage commenced at the end of 2006 when the program was scaled-up nationally. In order to guarantee treatment of pediatric patients, extensive training in the selection of appropriate ARV drug regimen and dosage was provided to doctors, often through on-site collaboration with domestic and international experts. The CCDC simultaneously established a pediatric ARV management system and a pediatric ART information system. CD4 count and other laboratory tests are being routinely performed on these pediatric patients. By the end of June 2009, 1529 pediatric patients had received ARV under the national program. However, challenges remain. Firstly, many children infected with HIV/AIDS live in rural areas where the treatment quality is hindered by the limited number of medical facilities and skilled medical workers. Secondly, much of the pediatric ARV drug supply depends on donation. An effort needs to be made by the Chinese Government to establish China's own drug procurement and supply system.
Asunto(s)
Antirretrovirales/uso terapéutico , Servicios de Salud del Niño/organización & administración , Atención a la Salud/organización & administración , Infecciones por VIH/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/prevención & control , Antirretrovirales/economía , Antirretrovirales/provisión & distribución , Niño , Servicios de Salud del Niño/normas , Preescolar , China/epidemiología , Atención a la Salud/normas , Femenino , Infecciones por VIH/prevención & control , Accesibilidad a los Servicios de Salud , Humanos , Masculino , Pediatría/normasRESUMEN
OBJECTIVE: To investigate the changes of the T lymphocytes and their subsets before and after receiving highly active anti-retroviral therapy (HAART) in children who were infected with HIV or AIDS patients. METHODS: Ninety-nine children met the criteria were recruited. All of them had received HAART in Guangxi Center for Disease Control and Prevention from May 2006 to April 2009. Peripheral blood of 2 milliliter was collected before treatment (D0) and after 3, 6, 12, 18, 24, 30, and 36 months (M3, M6, M12, M18, M24, M30 and M36), respectively. Four-color fluorescence flow cytometry was used for the detection of the absolute numbers of CD3(+), CD4(+), CD8(+) T lymphocytes in peripheral blood. And then, the percentages of CD3(+), CD4(+), CD8(+) T lymphocytes in the CD45(+) cells and the ratio of CD4/CD8 were calculated. RESULTS: Sixteen-five (65.66%) cases were treated with lamivudine (3TC)/zidovudine (AZT)/nevirapine (NVP), and 16 (16.16%), 8 (8.08%) and 10 (10.10%) cases were treated with 3TC/stavudine (D4T)/NVP, 3TC/AZT/efavirenz (EFV) and 3TC/AZT/lpv-rtv (LPV/r), respectively. The median of the ratio of CD4/CD8 were 0.39, 0.51, 0.61, 0.65, 0.70, 0.73 and 0.76 in M3, M6, M12, M18, M24, M30 and M36, respectively which were significantly higher than that in D0 (0.19) (Z values were -5.158, -7.375, -9.078, -8.853, -8.373, -5.845 and -5.844 respectively, P < 0.000). The median of CD4% were 16.92%, 22.70%, 25.54%, 26.66%, 27.99%, 30.36% and 29.30% respectively in M3, M6, M12, M18, M24, M30 and M36 respectively, which were also higher significantly than that in D0 (9.92%) (Z values were -5.268, -7.568, -9.496, -9.171, -8.760, -6.190 and -5.964 respectively, P < 0.000). In addition, the median of the absolute numbers of CD4(+)T lymphocytes in peripheral blood were 631, 813, 1050, 946, 1057, 1166 and 894 cells/mm(3) respectively in M3, M6, M12, M18, M24, M30 and M36, which were higher significantly than that of D0 (382 cells/mm(3)) (Z values were -3.318, -5.288, -6.661, -5.886, -5.801, -4.110 and -3.600 respectively, P < 0.000). However, the median of CD8% were 47.25%, 43.01%, 43.04%, 42.60%, 41.37%, 40.83% and 38.31% respectively in M3, M6, M12, M18, M24, M30 and M36, which were lower significantly than that of D0 (53.17%) (Z values were -3.082, -4.697, -5.282, -5.846, -5.757, -3.883 and -4.380 respectively, P < 0.001). CONCLUSION: There is certain rules for the changes of T lymphocytes and their subsets, which may play important roles in the evaluation of the therapeutic effect and the clinical application guidance of HAART.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/inmunología , Terapia Antirretroviral Altamente Activa , Infecciones por VIH/inmunología , Subgrupos de Linfocitos T , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Niño , Preescolar , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Lactante , Recuento de Linfocitos , MasculinoRESUMEN
OBJECTIVE: To study the clinicopathologic features, immunophenotype and prognosis of primary cutaneous anaplastic large cell lymphoma (C-ALCL). METHODS: Eight cases of C-ALCL were enrolled into the study. The clinicopathologic features, immunohistochemical findings and results of in-situ hybridization for EBER 1/2 were analyzed. RESULTS: Three of the 8 patients were males and 5 were females. The median age was 49.5 years. C-ALCL often presented with solitary skin nodule, without systemic symptoms. Histologically, the lymphoma cells infiltrated the dermis and subcutis in a sheet-like pattern. They were of large size and showed conspicuous nuclear atypia. Immunohistochemical study showed that more than 75% of the lymphoma cells were positive for CD30. All cases expressed one to three T cell markers (CD3, CD5 or CD45RO) and cytotoxic granule-associated antigens (TIA-1, granzyme B or perforin). The staining for leukocyte common antigen was positive in all cases, while the expression of CD5, CD8, ALK-1 and epithelial membrane antigen was noted in 5, 1, 1 and 3 cases, respectively. The staining for CD15, CD20, CK and HMB45 was negative. In-situ hybridization for EBER 1/2 was also negative in all the cases studied. Follow-up information was available in 6 patients. Five of them were still alive and 1 died of unclear cause. CONCLUSIONS: C-ALCL has distinctive clinicopathologic and immunophenotypic features. It is not Epstein-Barr virus-related and often carries a favorable prognosis.
Asunto(s)
Antígeno Ki-1/metabolismo , Linfoma Anaplásico Cutáneo Primario de Células Grandes/patología , Neoplasias Cutáneas/patología , Adulto , Anciano , Antígenos CD5/metabolismo , Niño , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Inmunofenotipificación , Hibridación in Situ , Antígenos Comunes de Leucocito/metabolismo , Linfoma Anaplásico Cutáneo Primario de Células Grandes/inmunología , Linfoma Anaplásico Cutáneo Primario de Células Grandes/metabolismo , Linfoma Anaplásico Cutáneo Primario de Células Grandes/terapia , Masculino , Persona de Mediana Edad , Pronóstico , ARN Viral/metabolismo , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/terapia , Adulto JovenRESUMEN
The magnetic properties of particulate matter (PM) deposited on the needles of Juniperus formosana along an urban street in Lanzhou city were measured to evaluate the variations of PM concentration in different seasons by varying distance from the road. The magnetism of PM deposited in this context was significantly higher in winter than in summer, which may reflect changes of atmospheric particle concentrations. Needle samples which were collected from the road-facing side exhibiting significantly stronger magnetism compared with those which were collected from the opposite side of the road, indicating the distance from pollution source to the needles as a factor controls the amount of PM. The results of this study show that the needles of Juniperus formosana are effective traps for PM and can therefore be used to monitor pollution fluxes in different seasons in an important urban context in NW China.
Asunto(s)
Contaminantes Atmosféricos/química , Monitoreo del Ambiente , Juniperus/química , Magnetismo , Material Particulado/química , Contaminantes Atmosféricos/análisis , China , Ciudades , Tamaño de la Partícula , Material Particulado/análisis , Estaciones del AñoRESUMEN
Leaf samples of Juniperus formosana were collected from an open road environment, in order to establish how particulate matter (PM) generated by vehicles was dispersed in both horizontal and vertical directions. Sampling was conducted at sites with trees of varying height and configuration adjacent to a major road in Lanzhou, Gansu Province, Northwest China. The concentration of remanence-bearing ferrimagnets in the leaf samples was estimated from measurements of Saturation Isothermal Remanent Magnetization (SIRM), while the weight of particles deposited on the leaves and their elemental composition were determined at different heights and in different directions relative to the road. The PM on the surface of needles was predominantly influenced by traffic emissions and by dust resuspension. Rows of roadside trees, as opposed to solitary trees, were more effective at intercepting PM and thus in filtering road traffic pollution. The results indicate that Juniperus formosana needles may be an effective bio-sensor for monitoring variations in the spatial diffusion of road pollutants.
Asunto(s)
Contaminantes Atmosféricos/análisis , Material Particulado/análisis , Árboles , China , Difusión , Polvo/análisis , Monitoreo del Ambiente , Magnetismo , Fenómenos Físicos , Hojas de la Planta/química , Emisiones de Vehículos/análisisRESUMEN
OBJECTIVE: To evaluate the 3-year outcomes of the Medecins Sans Frontieres/Guangxi Center for Disease Control and Prevention comprehensive and free of charge HIV/AIDS treatment and care project. METHODS: We present a detailed retrospective analysis of treatment outcomes of 432 cases who received highly active antiretroviral therapy (HAART) from December 2003 to December 2006. RESULTS: Among the adult patients who received HAART, the mortality rate was 6.5% and only 12 (2.8%) patients were lost to follow up. The mean CD4+ T cell count increase was 147 cells/microl and 246 cells/microl for patients receiving HAART for 9-15 and 21-27 months respectively. An adherence assessment conducted during March to December 2006 indicated that 95.9% of the study cases reached an adherence of 95% or more of the prescribed medications. Among the 30 children patients who received HAART, 4 (13.3%) cases died and the mean CD4+ T cell increase after 9-15 and 21-27 months of HAART was 673 cells/microl and 658 cells/microl respectively. 148 of the adult patients starting HAART were current or ex-intravenous drug users (IDU) and showed global death rate and lost to follow-up rate comparable to those of non-IDU patients (Log rank test, P = 0.91). CONCLUSIONS: Good mid-term therapeutic outcomes with combination antiretroviral therapy have been achieved in this project. Total free of charge care and treatment and intensive patient support/ counseling are crucial to program success.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Terapia Antirretroviral Altamente Activa , Infecciones por VIH/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/mortalidad , Síndrome de Inmunodeficiencia Adquirida/prevención & control , Adulto , Recuento de Linfocito CD4 , Preescolar , China , Femenino , Estudios de Seguimiento , Infecciones por VIH/mortalidad , Infecciones por VIH/prevención & control , Humanos , Lactante , Recién Nacido , Masculino , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Medicina Preventiva/organización & administración , Medicina Preventiva/estadística & datos numéricos , Estudios Retrospectivos , Tasa de Supervivencia , Factores de TiempoRESUMEN
OBJECTIVE: To assess the efficacy of Mytrolimus (CCI-779), a derivative of rapamycin, eluting stents in preventing restenosis in the porcine model. METHODS: The bare stents (n = 10), stents coated with polyolefin (n = 10) or stents coated with Mytrolimus (160 microg/18 mm) in polyolefin (n = 8) were implanted in left anterior descending coronary arteries or right coronary artery of mini-swine. Coronary angiography was performed after 4 weeks then the animals were sacrificed. The cross sections of the stented coronary arteries were analyzed, the injury score, luminal area, neointimal thickness above the struts and between the struts of stents, neointimal area and percentage of restenosis were measured. RESULTS: The mean injury scores and luminal area were similar in three groups. There was no difference in above-stated items between the polyolefin coating stent and bare mental stent. To compare Mytrolimus-eluting stent with bare-stent, neointimal thickness above the struts [(0.18 +/- 0.08) mm vs (0.33 +/- 0.25) mm, P < 0.05] and between the struts [(0.14 +/- 0.05) mm vs (0.28 +/- 0.23) mm, P < 0.05] and neointimal area [(1.09 +/- 0.24) mm(2) vs (2.44 +/- 1.59) mm(2), P < 0.05] were significantly decreased in the Mytrolimus-eluting stent group than in bare mental stent group. Compared with bare-stent, the Mytrolimus eluting stent was associated with a 55.33% reduction in neointimal area. No restenosis developed in the Mytrolimus group. CONCLUSION: The Mytrolimus-eluting stents can effectively inhibit the neointimal hyperplasia in stented areas of coronary arteries 4 weeks after stent implantation in porcine model.
Asunto(s)
Implantación de Prótesis Vascular , Reestenosis Coronaria/prevención & control , Stents Liberadores de Fármacos , Sirolimus/análogos & derivados , Animales , Enfermedad de la Arteria Coronaria/terapia , Sirolimus/farmacología , Sirolimus/uso terapéutico , PorcinosRESUMEN
OBJECTIVE: To identify patients with endometrial cancer with potential Lynch-related DNA mismatch repair (MMR) protein expression defects and to explore the role of these defects in screening for LS. METHODS: Endometrial cancers from 173 patients recruited to the Nanchong Central Hospital were tested for MMR (MLH1, MSH2, PMS2, and MSH6) protein expression using immunohistochemistry (IHC). RESULTS: In the 173 tumor tissue samples, the expression loss rates of MSH6, MSH2, PMS2 and MLH1 protein were 16.18% (28/173), 12.14% (21/173), 7.51% (13/173) and 5.78% (10/173), respectively. The total loss rate of MMR protein was 29.89% (27/87). There were 19 patients with a family history of cancer, of which 18 patients demonstrated loss of expression of MMR protein. In the 22 abnormal MMR patients without family history, five families were found to have Lynch-associated cancer (colorectal cancer, endometrial cancer, ovarian cancer, stomach cancer) after follow-up for two years. CONCLUSION: MMR proteins play an important role in the progress of endometrial cancer. The routine testing of MMR proteins in endometrial cancer can contribute to the screening of LS families, especially small families.
Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias Colorrectales Hereditarias sin Poliposis/química , Reparación de la Incompatibilidad de ADN , Neoplasias Endometriales/química , Proteínas Adaptadoras Transductoras de Señales/análisis , Adenosina Trifosfatasas/análisis , Adulto , Anciano , China , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Reparación de la Incompatibilidad de ADN/genética , Enzimas Reparadoras del ADN/análisis , Proteínas de Unión al ADN/análisis , Detección Precoz del Cáncer/métodos , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Femenino , Predisposición Genética a la Enfermedad , Herencia , Hospitales Generales , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto , Homólogo 1 de la Proteína MutL , Proteína 2 Homóloga a MutS/análisis , Proteínas Nucleares/análisis , Linaje , Fenotipo , Valor Predictivo de las Pruebas , Factores de RiesgoRESUMEN
Immune activation and IL-7/IL7 receptor (CD127) systems are significant for CD4+ T cell defect in AIDS patients. However, the association between immune activation and CD127 expression on T lymphocyte subsets in Chinese pediatric AIDS patients is not well studied. Here, we recruited a cohort of 194 Chinese pediatric AIDS patients: 135 good viral responders (GVRs) and 59 poor viral responders (PVRs). CD38high and HLA-DR+CD8+ T lymphocytes and CD127 expression on T-cell subsets were determined by flow cytometry. Viral load was detected using a quantitative RT-PCR assay. The results showed that pediatric AIDS patients had a lower memory CD4+ percentage and a higher memory CD8+ T-cell percentage. The percentage of naive CD4+T-cells was higher, especially in GVRs. The percentage of CD38high and HLA-DR+CD8+ in PVRs was higher than in GVRs and controls, being positively correlated with viral load and memory CD8+, but negatively correlated with memory CD4+ T cells. The percentage of CD127+ memory CD4+ T cells in GVRs was higher than in PVRs, but lower than in controls. CD127 expression was positively correlated with percentage of CD4+ subsets and naive CD8+ T cells, but negatively correlated with percentage of memory CD8+ T cells. Our study demonstrates that the percentages of CD38high and HLA-DR+ CD8+ T cells are good markers to evaluate immune activation of pediatric AIDS patients, and elevated immune activation has a more profound effect on memory T cells. IL- 7/CD127 system is more important to maintain the proportion of naive T cells.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/inmunología , Pueblo Asiatico/estadística & datos numéricos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , VIH-1/inmunología , Antígenos HLA-DR/inmunología , Subunidad alfa del Receptor de Interleucina-7/inmunología , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Síndrome de Inmunodeficiencia Adquirida/virología , Adolescente , Niño , China/epidemiología , Estudios Transversales , Progresión de la Enfermedad , Femenino , Citometría de Flujo , Humanos , Memoria Inmunológica , Activación de Linfocitos , Masculino , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Carga Viral , Replicación ViralRESUMEN
BACKGROUND: Six provinces in China accounted for 70% - 80% of all reported HIV/AIDS cases in the country in 2009 and five provinces accounted for 78% of all reported mother-to-child transmission (MTCT) of HIV cases. Because Guangxi belonged to both groups, the Prevention of Mother-to-Child Transmission (PMTCT) Plus program was established there to understand better low birth weight (LBW) and preterm delivery (PD) birth outcomes and their associated risk factors better. METHODS: Pregnancy outcomes were examined among HIV-infected pregnant women who enrolled in the PMTCT Plus program from June 2006 to February 2009 in Guangxi, China. Multivariate Logistic regression analysis was used to explore the risk factors associated with LBW (< 2500 g) and PD (gestational age < 37 weeks). RESULTS: The prevalence of LBW and PD among 194 HIV-positive mothers was 19.6% (38/194) and 9.8% (19/194), respectively. Multivariate Logistic regression analysis showed that CD4 cell count < 100 cell/µl (multivariate-adjusted odds ratio (AOR) 5.52; 95%CI 1.11 - 25.55) and CD4 cell count 100 - 199 cells/µl (AOR 3.40; 95%CI 1.03 - 11.25, compared to CD4 cell count ≥ 350 cells/µl), gestational age < 37 weeks (AOR 4.38; 95%CI 1.29 - 14.82, compared to ≥ 37 weeks), maternal weight < 45 kg (AOR 5.64; 95%CI 1.09 - 29.07) and maternal weight 45 - 54 kg (AOR 3.55; 95%CI 1.31 - 9.60, compared to ≥ 55 kg) at enrollment, and HIV RNA ≥ 100 000 copies/ml at enrollment (AOR 4.22; 95%CI 1.24 - 14.32) and 20 000 - 99 999 (AOR 2.77; 95%CI 1.01 - 7.77, compared to < 20 000 copies/ml) were associated with a higher risk of LBW. For PD, only maternal injection drug use as the route of HIV transmission (AOR 5.30; 95%CI 1.33 - 21.14, compared to those infected with HIV through sexual transmission) was significantly associated with a higher risk of PD. CONCLUSIONS: Lower CD4 cell count and higher HIV RNA viral load at enrollment were associated with LBW. Optimal antenatal care, including earlier antenatal screening and HIV diagnosis, is critical to earlier PMTCT prophylaxis and/or HIV treatment to prevent transmission of HIV to the infant and also to prevent LBW pregnancy outcomes.
Asunto(s)
Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Recién Nacido de Bajo Peso/fisiología , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Adolescente , Adulto , Recuento de Linfocito CD4 , China/epidemiología , Femenino , Edad Gestacional , Humanos , Recién Nacido , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Factores de Riesgo , Carga Viral , Adulto JovenRESUMEN
BACKGROUND: The initiation and expansion of China's national free antiretroviral therapy program has led to significant improvement of survival among its participants. Success of further scaling up treatment coverage rests upon intensifying HIV screening and efficient linkage of care. Timely CD4 cell count testing after HIV diagnosis is necessary to determine whether a patient meets criteria for antiretroviral treatment, and represents a crucial link to engage HIV-infected patients in appropriate care, which has not been evaluated in China. METHODS: We evaluated all patients ≥ 16 years who tested HIV positive from 2005 to 2009 in Yunnan and Guangxi. Multivariate Logistic regression models were applied to identify factors associated with lack of CD4 cell count testing within 6 months after HIV diagnosis. RESULTS: A total of 83 556 patients were included. Over the study period, 30 635 (37%) of subjects received a CD4 cell count within 6 months of receiving the HIV diagnosis. The rate of CD4 cell count testing within 6 months of HIV diagnosis increased significantly from 7% in 2005 to 62% in 2009. Besides the earlier years of HIV diagnosis, negative predictors for CD4 cell count testing in multivariate analyses included older age, not married or unclear marriage status, incarceration, diagnosis at sexual transmitted disease clinics, mode of HIV transmission classified as men who have sex with men, intravenous drug users or transmission route unclear, while minority ethnicity, receipt of high school or higher education, diagnosis at voluntary counseling and testing clinics, and having HIV positive parents were protective. CONCLUSIONS: Significant progress has been made in increasing CD4 testing among newly diagnosed HIV positive patients in Yunnan and Guangxi from 2005 - 2009. However, a sizable proportion of HIV positive patients still lack CD4 testing within 6 months of diagnosis. Improving CD4 testing, particularly among patients with identified risk factors, is essential to link patients with ART services and optimize treatment coverage.
Asunto(s)
Recuento de Linfocito CD4 , Infecciones por VIH/inmunología , Adulto , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Humanos , Modelos Logísticos , MasculinoRESUMEN
Ge-gen (Radix Puerariae) is used in traditional oriental medicine for various medicinal purposes. The drug is the root of a wild leguminous creeper, Pueraria lobata (Willd) Ohwi. It possesses a high content of avonoid derivatives, the most abundant of which is puerarin. Our goal was to find the effect of puerarin on cytochrome P450 enzymes in vivo. The study was conducted in 18 male volunteers of different genotypes (CYP2D6 *1/*1, *1/*10, *10/*10). Plasma was obtained at 6 h after oral administration and urine was collected from 0 to 8 h after probe drug administration. The logarithm value of metabolic rate decrease from -0.0055 +/- 0.1887 to -0.1754 +/- 0.2411 implied puerarin inhibited activity of CYP2D6. There was no significant relationship between the inhibition with the CYP2D6 genotypes. The paraxanthin/caffeine ratio in the plasma sample at 6th hour was increased by 30 +/- 47% (p = 0.003), implied puerarin induced the activity of CYP1A2. While puerarin used together with the substrates of both enzymes, drug interaction worth the attention and at sometimes precautions are needed.
Asunto(s)
Citocromo P-450 CYP1A2/efectos de los fármacos , Citocromo P-450 CYP2D6/efectos de los fármacos , Isoflavonas/efectos adversos , Adulto , Cafeína/farmacocinética , Citocromo P-450 CYP2D6/genética , Interacciones Farmacológicas , Genotipo , Humanos , Masculino , Metoprolol/farmacocinética , Distribución AleatoriaRESUMEN
BACKGROUND: Pulmonary tuberculosis (PTB) among asymptomatic Chinese patients with HIV infection has not been investigated despite high tuberculosis burden in China. This study was aimed to evaluate the prevalence, risk factors and clinical outcomes of PTB among asymptomatic patients with HIV/AIDS in Guangxi to facilitate the development of diagnostic and treatment strategies. METHODS: All asymptomatic adult HIV-infected patients with CD4 < 350 cells/µl who attended four HIV clinics in Guangxi between August 2006 and March 2008 were evaluated for active PTB with physical examination, chest X-ray (CXR), sputum smear and/or sputum liquid culture. Data were described using median (interquartile range, IQR) and frequencies. Univariate and multivariate Logistic regression analyses were performed to identify risk factors associated with PTB. RESULTS: Among 340 asymptomatic subjects, 15 (4%) were diagnosed with PTB, with 4 (27%) sputum smear positive and 8 (53%) sputum culture positive. CXR has higher diagnostic sensitivity (87%) than sputum smear (25%) and sputum culture (67%), but lower specificity (56%) compared with sputum smear (99%) and culture (100%). In univariate analysis, injection drug user, body mass index (BMI) < 18 kg/m(2), CD4 < 50 cells/µl and presence of peripheral lymphadenopathy were associated with an increased risk of asymptomatic PTB, while in multivariate analysis only peripheral lymphadenopathy maintained statistical significance (OR = 7.6, 95%CI 1.4 - 40). Patients with negative smear and minor or no abnormalities on CXR had longer interval between screening and TB treatment. CONCLUSIONS: PTB was relatively common in this group of HIV(+) asymptomatic Chinese patients. Diagnosis is challenging especially where sputum culture is unavailable. These findings suggest that an enhanced evaluation for PTB needs to be integrated with HIV care in China and transmission prevention in China to control at both households and health care facilities, especially for patients with factors associated with a higher risk of PTB.