RESUMO
To identify the integration sites in the host genome for the hepatitis B virus (HBV)-encoded X protein (HBx) in hepatocellular carcinoma (HCC) biopsies that are positive for hepatitis B surface antigen (HBsAg). HCC biopsies were obtained from six patients that were HBV carriers, as demonstrated by the presence of HBsAg in their serum and sero-negativity for antibody to HBsAg. DNA was extracted from the tissue, fractionated, and circularized. Primers were designed according to the HBx sequence and used to amplify the circularized DNA templates by inverse polymerase chain reaction (IPCR). The amplified DNA fragments were checked by electrophoresis, cloned into the PMD18-T expression vector, and sequenced. Sequence alignment was performed by the Blast algorithms. Seven electrophoresis bands yielded 22 sequencing results, which represented a total of three HBx integration sites in the host genome: 19q12, 2q32.2, 22q12. The 19q12 integration site encompasses the CCNE1 gene, which encodes a G1/S-specific cyclin-E1. HBx-related integration sites exist in HBsAg-positive HCC biopsies. The CCNE1 gene may play a role in the development of HBx-related HCC.
Assuntos
Carcinoma Hepatocelular/genética , Vírus da Hepatite B/fisiologia , Neoplasias Hepáticas/genética , Transativadores/genética , Integração Viral , Carcinoma Hepatocelular/sangue , Ciclina E/genética , Primers do DNA , DNA Viral/genética , Antígenos de Superfície da Hepatite B/metabolismo , Vírus da Hepatite B/genética , Humanos , Neoplasias Hepáticas/sangue , Proteínas Oncogênicas/genética , Proteínas Virais Reguladoras e AcessóriasRESUMO
OBJECTIVE: This study aimed to evolution of genotypic drug resistance prevalence in treatment-failing patients in Shenzhen. METHODS: Peripheral venous blood samples were collected from 41 AIDS patients whom failing combination antiretroviral therapy, and were amplified by nested PCR; then the amplified fragments were sequenced and analyzed. RESULTS: Partial pol sequences of 38 samples were successfully amplified, and 3 samples have not found any mutations in their pol sequences. K103N, G190A, Y181C, K101P, M184V, D67N, K70R, T215Y and K219 were most common mutations. According to the genotypic analysis, 100% of the patients (35/35) showed high and intermediate level resistance to nevirapine (NVP) and efavirenz (EFV); above 50% of the patients showed high and intermediate level resistance to zidovudine (AZT), lamivudine (3TC), stavudine (D4T) and didanosine (DDI); only a few patients showed intermediate and low level drug resistance to protease inhibitors (PIs). Patients whom take D4T + DDI + NVP regimens were most common to appear drug mutation. CONCLUSIONS: The high prevalence of drug resistance to NNRTIs and NRTIs among patients failing combination antiretroviral therapy in Shenzhen. That is the main reason for treatment failure in AIDS patients. Now most of mutations were detected against NNRTIs and NRTIs, only a few against PIs. Our finding suggested that a second-line antiretroviral therapy regimens is needed among the patients failing therapy and the boosted-PIs maybe are good choice.
Assuntos
Síndrome da Imunodeficiência Adquirida/virologia , Farmacorresistência Viral/genética , HIV-1/genética , Mutação , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Adulto , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Evolução Molecular , Feminino , HIV-1/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral , Falha de Tratamento , Adulto JovemRESUMO
OBJECTIVE: To evaluate the value of chest CT findings and dynamic changes of viral load in patients with novel influenza A (H1N1) infection in clinical diagnosis, differential diagnosis and treatment. METHODS: Fifty-one patients with confirmed novel influenza A (H1N1) according to the diagnostic criteria of the Ministry of Health, received chest X-ray, CT scans (HRCT) and viral load tests in our hospital from May to December of 2009. Based on whether there were signs of pneumonia in CT imaging, the patients were divided into a pneumonia group (n = 31) and a non-pneumonia group (n = 20). The relationship between chest CT changes and viral load was observed and analyzed statistically using SPSS 10.5 software. RESULTS: Patchy consolidations of lungs were the main findings in pneumonia group with influenza A (H1N1) infection, and ground-glass opacities were the main CT findings at acute and convalescent phases. Lobular and segmental shadows of the lungs were diffusely distributed, mostly found in lower lungs, especially the left lung. In some cases, the lung diseases were accompanied with mediastinal lymphadenopathy. Co-existence of pulmonary parenchymal, interstitial and pleural diseases was observed. Peak viral load occurred at the early phase of illness, with the mean initial viral load being 7.7 copies/ml and 4.2 copies/ml in the pneumonia and the non-pneumonia groups respectively. The viral nucleic acid became negative 4 days after antiviral treatment (course of 6 days). Dynamic observation of 3 patients with novel influenza A (H1N1) pneumonia showed that, the viral clearance period preceded the absorption of lung lesions in 2 cases, but viral clearance period of a young patient was significantly prolonged. CONCLUSION: In patients with the novel influenza A (H1N1) infection, the viral load in the pneumonia group was significantly higher than that in the group with normal chest imaging. Dynamic observation on chest imaging and viral load may be beneficial for clinicians to start prompt and effective treatment.
Assuntos
Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/diagnóstico por imagem , Influenza Humana/virologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Influenza Humana/epidemiologia , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Tomografia Computadorizada por Raios X , Carga Viral , Adulto JovemRESUMO
OBJECTIVE: To investigate whether the CD4+CD25+Foxp3+ regulatory T cells are associated with serum TGF beta 1 in patients with hepatitis B. METHODS: Patients with chronic hepatitis B (CHB), chronic asymptomatic carriers (AsC), normal subjects (NS) and the resolved from HBV infection (Resolved) were recruited in this study. Flow cytometric analysis was used to detect the frequency and phenotype of peripheral CD4+CD25+Foxp3+ T cells, and Foxp3 gene expression were examined by real time PCR. Serum TGF beta 1 levels were measured by ELISA (enzyme-linked immunosorbent assay). RESULTS: Patients with CHB or AsC exhibited significantly higher frequency of CD4+CD25+Foxp3+ T cells compared to healthy controls. CD4+CD25+ T cells derived from patients with CHB and AsC expressed higher level of Foxp3-mRNA. Furthermore, the frequency of CD4+CD25+Foxp3+ regulatory T cells was correlated with serum HBV DNA copy numbers in patients with CHB and AsC. Our results indicated that the serum TGF beta was increased in CHB and AsC patients compared to control patients, and that serum TGF beta was correlated with the expression of Foxp3-mRNA and the frequency of CD4+CD25+Foxp3+ regulatory T cells in patients with CHB and AsC. CONCLUSIONS: The findings have important implication in the understanding of the role and mechanism of aberrant CD4+CD25+Foxp3+ regulatory T cells in the maintenance of chronicity in hepatitis B patients.
Assuntos
Fatores de Transcrição Forkhead/metabolismo , Hepatite B Crônica/imunologia , Linfócitos T Reguladores/imunologia , Fator de Crescimento Transformador beta/sangue , Adolescente , Adulto , Antígenos CD4/imunologia , Antígenos CD4/metabolismo , Portador Sadio/sangue , Portador Sadio/imunologia , Feminino , Citometria de Fluxo , Fatores de Transcrição Forkhead/imunologia , Antígenos de Superfície da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Hepatite B Crônica/sangue , Humanos , Subunidade alfa de Receptor de Interleucina-2/imunologia , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Masculino , Fenótipo , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Linfócitos T Reguladores/virologia , Carga Viral , Adulto JovemRESUMO
OBJECTIVE: To investigate the effects of inactivation of CD(4)(+)CD(25)(+) regulatory T cells (Treg) combined with the administration of levofloxacin (LFX) on the cellular immune response of murine tuberculosis. METHODS: Inactivation of Treg was achieved by intraperitoneal injection of anti-CD(25), clone PC61. Female C57BL/6 mice were divided into 4 groups, PC61 alone, LFX alone, PC61 plus LFX, and the control, with 19 mice in each group. The LFX group and the control group were treated with rat-IgG isotope control. Mice were inoculated with H(37) Rv (1 x 10(6) CFU) via the tail vein 3 days later. From the 2nd day, the LFX group and the PC61 plus LFX group received intragastric administration of LFX at 200 mg x kg(-1) x d(-1) per mouse for 45 days. Blood and spleen Tregs were measured by flow cytometry. The cellular immune response and pulmonary histopathology at different time points were also evaluated after infection. RESULTS: At the 10th and 30th day, the ratio of CD(4)(+)CD(25)(+)/CD(4)(+)T cells in the spleen was (30 +/- 4)% and (17.3 +/- 1.6)% respectively in the control group, (21 +/- 4)% and (16.1 +/- 1.3)% respectively in the PC61 group, (44 +/- 6)% and (24.7 +/- 2.0)% respectively in the LFX group, (24 +/- 3)% and (10.4 +/- 1.0)% respectively in the PC61 plus LFX group. The differences were significant between groups (q = 3.62 - 5.56, P < 0.05), but the difference between the PC61 plus LFX group and the PC61 group at the 10th day. Same results were obtained from the peripheral blood. PC61 plus LFX therapy resulted in BCG specific cytokine response (IL-17, IFN-gamma, TNF-alpha) from murine spleen cells at the 10th and the 30th day, and also in milder pathologic changes and the lowest mortality. CONCLUSIONS: The cellular immune response was enhanced by Treg inactivation and LFX therapy, which decreased the pathologic changes and the mortality of murine tuberculosis.
Assuntos
Antibacterianos/uso terapêutico , Levofloxacino , Ofloxacino/uso terapêutico , Linfócitos T Reguladores/imunologia , Tuberculose Pulmonar/tratamento farmacológico , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Tuberculose Pulmonar/imunologiaRESUMO
OBJECTIVE: To obtain the purified early secretory antigenic target-6 (ESAT-6) protein and to evaluate its application in detection of Mycobacterium tuberculosis antigen-specific interferon-gamma (IFN-gamma) response. METHODS: ESAT-6 protein was expressed by genetic engineering. The antigen specificity and reactivity of ESAT-6 were evaluated by Western blot. Using ESAT-6 as the antigen, the antigen-specific IFN-gamma response in patients with tuberculosis, healthy medical workers, and village residents was detected by the Elispot method. The results were also compared with those obtained by a commercial kit (QuantiFERON-TB-GOLD, QFT-G). RESULTS: ESAT-6 protein was successfully expressed and purified, and the antigen specificity of ESAT-6 was confirmed by its recognition by the antigen-specific antibody (anti-ESAT-6). The specificity and sensitivity of the Elispot assay using ESAT-6 as the antigen in detecting the IFN-gamma response was comparable with those of the commercial kit (QFT-G). The positive rates of the Elispot assay for patients with tuberculosis, healthy medical workers and villagers were 36/49 (73.5%), 11/62 (17.7%), and 17/194 (8.8%), respectively, while the rates of the OFT-G method for patients with tuberculosis and healthy medical workers were 38/49 (77.6%) and 14/58 (24.1%), respectively. The sensitivity (73.5%, 77.6%; chi2 = 0.381, P > 0.05) and specificity (82.3%, 75.9%; chi2 = 0.406, P > 0.05) of these two methods did not differ significantly. CONCLUSIONS: Recombinant ESAT-6 protein was expressed and purified. Elispot using recombinant ESAT-6 protein as antigen showed high sensitivity and specificity for detection of Mycobacterium tuberculosis antigen-specific IFN-gamma response. The purified ESAT-6 can be used for diagnosis of Mycobacterium tuberculosis infection.
Assuntos
Antígenos de Bactérias/isolamento & purificação , Proteínas de Bactérias/isolamento & purificação , Interferon gama/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose/diagnóstico , Adolescente , Adulto , Idoso , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Interferon gama/sangue , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Proteínas Recombinantes/isolamento & purificação , Sensibilidade e Especificidade , Tuberculose/imunologia , Adulto JovemRESUMO
BACKGROUND: The diagnosis of active pulmonary tuberculosis (TB) remains a challenge in clinic, especially for sputum negative pulmonary TB. Bronchoalveolar lavage fluid (BALF) has higher sensitivity than sputum for detection of Mycobacterium tuberculosis (Mtb). However, bronchoscopy is invasive and costly, and not suitable for all patients. In order to make TB patients get more benefit from BALF for diagnosis, we explore which indicator might be used to optimize the choice of bronchoscopy. METHODS: A total of 1539 sputum-smear-negative pulmonary TB suspects who underwent bronchoscopy were recruited for evaluation. The sensitivity, specificity and accuracy of Mtb detection in sputum and BALF were compared. Odds ratios and 95% confidence intervals were used to assess variables that associated with positive acid-fast bacilli (AFB) smear, Mtb culture and nucleic acid amplification test (NAAT) of BALF in sputum-negative and non-sputum-producing pulmonary TB suspects. RESULTS: BALF has significantly higher sensitivity (63.4%) than sputum (43.5%) for Mtb detection by culture and NAAT. 19.7% (122/620) sputum-negative and 40.0% (163/408) non-sputum-producing suspects had positive bacteriological results in BALF. Among sputum-negative and non-sputum-producing pulmonary TB suspects, the positivity of Mtb detection in BALF is associated with a younger age, the presence of pulmonary cavities and a positive result of interferon-gamma release assay (IGRA). Sputum-negative patients under 35 years old with positive IGRA and pulmonary cavity had 84.8% positivity of Mtb in BALF. CONCLUSIONS: Our study indicated that combination of age, the presence of pulmonary cavity, and the result of IGRA is useful to predict the positivity of Mtb detection in BALF among sputum-negative and non-sputum producing pulmonary TB suspects. Those who are under 35 years old, positive for the presence of pulmonary cavity and IGRA, should undergo bronchoscopy to collect BAFL for Mtb tests, as they have the highest possibility to get bacteriologically confirmation of TB.
Assuntos
Líquido da Lavagem Broncoalveolar/microbiologia , Mycobacterium tuberculosis , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/epidemiologia , Adulto , Idoso , Feminino , Humanos , Testes de Liberação de Interferon-gama , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Radiografia Torácica , Estudos Retrospectivos , Fatores de Risco , Escarro/microbiologia , Adulto JovemRESUMO
OBJECTIVE: In order to take an insight into the profile of HIV/AIDS and tuberculosis (TB) co-infection, we made a statistic survey in 9 hospitals in mainland China. With the purpose of guiding the prevention and treatment, 241 cases with such co-infection were enrolled and the data with respect to clinical manifestations, laboratory tests, therapy and prognosis were analysed. METHODS: All indices were collected with unified questionary. RESULTS: Young men (75.9%) took constituted the majority. HIV was transmitted mainly by intravenous drug use (IDU) in Xinjiang and Yunnan provinces, by blood transfusion or blood products in Shanghai, Henan and Wenxi county of Shanxi, and by sexual transmission in Fuzhou, Shanghai, Shenzhen and Dehong prefecture of Yunnan province. In this survey, pulmonary TB accounted for 59.3%, extra-pulmonary TB for 21.2%, and both for 19.5% of the patients. As for laboratory tests, only 9.5% was positive in sputum for acid-fast bacillus (AFB) and 2.9% in culture, 10.8% of the patients had AFB in pleural fluid or cerebrospinal fluid. Besides, PPD was negative or weakly positive in most of the cases. Overall, 76.8% of the 241 cases had a CD(4) cell count < 200/microl, and 58.5% < 100/microl. 80.5% of the patients was treated with anti-tuberculous medications and 69.7% with highly active antiretroviral therapy (HAART). 203 (84.2%) were still alive and 38 (15.8%) died. CONCLUSIONS: (1) The clinical manifestations of the 241 cases were varied because of prevailing pulmonary TB. (2) The immune function was depressed with reducing CD(4) counts in most of the patients. (3) Positivity rate of examination relevant to TB was too low to help the diagnosis. (4) The mortality (15.8%) was high even with HAART and/or chemotherapy.
Assuntos
Síndrome da Imunodeficiência Adquirida/epidemiologia , Infecções por HIV/epidemiologia , Tuberculose/epidemiologia , Adulto , Antituberculosos/uso terapêutico , Contagem de Linfócito CD4 , China/epidemiologia , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Prognóstico , Tuberculose/tratamento farmacológicoRESUMO
OBJECTIVE: To study into the genetic polymorphism of DC-SIGN and DC-SIGNR's exon 4 in Chinese hepatitis C patients and its relationship with HCV infection susceptibility. METHODS: Patients with hepatitis C (n=300, group A) and healthy subjects (n=520, group B) were genotyped and analysed for the repeat sequence of polymorphism of DC-SIGN and DC-SIGNR's exon 4 using PCR and DNA sequencing. RESULTS: The distribution of genotypes and alleles in DC-SIGN's exon 4 in the two groups did not differ significantly (P > 0.05). The difference of allele frequency in DC-SIGNR's exon 4 between the two groups was also not significant (P > 0.05). However, 9/5 genotype distribution frequency of DC-SIGNR's exon 4 in patients with hepatitis C was significantly higher than that in the healthy subjects (P < 0.05). CONCLUSION: There is no significant correlation between the genetic polymorphism of DC-SIGN's exon 4 and HCV infection susceptibility. 9/5 genotype distribution frequency of DC-SIGNR's exon 4 in patients with hepatitis C is significantly higher and may be associated with HCV infection susceptibility.
Assuntos
Moléculas de Adesão Celular/genética , Predisposição Genética para Doença , Hepatite C Crônica/genética , Lectinas Tipo C/genética , Polimorfismo Genético , Receptores de Superfície Celular/genética , Adolescente , Adulto , Idoso , Povo Asiático/genética , Doadores de Sangue , Estudos de Casos e Controles , Criança , Éxons , Feminino , Genótipo , Hepatite C Crônica/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: To understand the genetic polymorphism of DC-SIGN's and DC-SIGNR's neck regions in normal Chinese Han population, and to obtain the genetic data of the two loci in Chinese Han population. METHODS: The genotypes and alleles of repeat sequences of DC-SIGN and DC-SIGNR neck region were typed by PCR, agarose gel electrophoresis and sequencing. Polymorphism information content (PIC) of DC-SIGNR was calculated. RESULTS: DC-SIGN genetic polymorphism was rare. Allele 7 was most and its frequency was 0.9808. 4-, 5-, 6- and 8- alleles were also found, although their frequencies were very low. Caucasians had only 6- and 8- allele mutants; DC-SIGNR genetic polymorphism was high, its PIC was 0.5312, 4-,5-,6-,7-,8-,9- alleles and 16 genotypes were found in normal Chinese Han population. The differences of 6/5,7/4,7/5,7/6,7/7,9/5,9/7,9/9 genotypes distribution and 5-,6-,7-,9- alleles frequency between normal Chinese Han population and Caucasian population were all extremely distinct (P<0.01). The inserted mutation seemed more in Chinese Hans than Caucasian population. CONCLUSION: DC-SIGN and DC-SIGNR genotypes and alleles distribution in Chinese Han population are significantly different from Caucasian population and with Chinese own population genetic characteristics, compared with Caucasians.
Assuntos
Moléculas de Adesão Celular/genética , Lectinas Tipo C/genética , Polimorfismo Genético/genética , Receptores de Superfície Celular/genética , Adolescente , Adulto , Alelos , Povo Asiático/genética , China , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Reação em Cadeia da Polimerase , Adulto JovemRESUMO
OBJECTIVES: To study the effect of using lamivudine to prevent fulminant hepatic failure (FHF) in patients with chronic hepatitis B. METHODS: 164 patients were randomly put into a conventional supporting treatment control group and a lamivudine treatment group. In the latter, 82 patients were given lamivudine orally at a dose of 100 mg every day besides the support care which was also given to the control group. RESULTS: The rate of deterioration to chronic severe hepatitis in the lamivudine treatment group was significantly lower than that of the control group (23.2% vs. 46.3%, P < 0.01). 52.6% (20/38) with chronic severe hepatitis in the control group died. Only 26.3% (5/19) in the lamivudine treatment group succumbed to terminal liver disease (P < 0.01). There was a significant difference between the two groups in regards to the complication incidence of gastrointestinal bleeding, infections, hepatic coma, and kidney failure (P < 0.05). In addition, the recovery of liver function and liver fibrosis, and the rates of HBeAg loss and seroconversion in the lamivudine treatment group were better than those in the control group. Furthermore, the serum HBV DNA levels decreased more rapidly and continued to be substantially suppressed in the lamivudine treatment group. CONCLUSIONS: Our results suggest that lamivudine administration with improved support care not only is likely to prevent chronic severe hepatitis occurrence in patients with chronic viral hepatitis B of a severe degree, but also shows some efficacy in preventing FHF.
Assuntos
Hepatite B Crônica/tratamento farmacológico , Lamivudina/uso terapêutico , Falência Hepática Aguda/prevenção & controle , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Transcriptase Reversa/uso terapêuticoRESUMO
OBJECTIVE: To investigate the level of specific cellular immunity in patients with active pulmonary tuberculosis and its potential relationship with severity of the disease. METHODS: Thirty active pulmonary tuberculosis patients with positive tubercle bacilli in sputum were enrolled for the study. Immune responses including lymphocytes proliferation enhanced by enhance intracellular survival (EIS) antigen and cytokine production including interferon-gamma (IFN-gamma) and interleukin-10 (IL-10), were assayed. Cell proliferation was determined by methyl thiazolyl tetrazolium (MTT), while cytokine production was quantified by enzyme linked immunoadsorbent assay (ELISA). The results were compared to those of 20 healthy individuals and 16 persons recovered from tuberculosis. RESULTS: Cell proliferation response and IFN-gamma production were significantly higher in patients convalescent from tuberculosis compared to patients with active pulmonary tuberculosis, EIS antigen was found to elicit a dominant Th2 cytokine response. CONCLUSION: Impaired Th1 immune response to EIS is observed in patients with active pulmonary tuberculosis. Induction of imbalance of Th1/Th2 immune response may be the main action of EIS, which may be a factor of pathogenesis of tuberculosis.
Assuntos
Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Imunidade Celular , Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/imunologia , Acetiltransferases , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Interferon gama/imunologia , Ativação Linfocitária , Masculino , Células Th1/imunologia , Adulto JovemRESUMO
Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma in the adult population, and treatment of DLBCL is still unfavorable. Therefore, there is an urgent requirement to investigate the molecular mechanisms underlying DLBCL tumorigenesis. To study the potential function of microRNA-155 (miR-155) involved in the regulation of lymphoma, we monitored lymphoma cell behavior including proliferation, cell cycle, and apoptosis using CCK-8 and flow cytometry analysis. Real-time PCR was used to detect the expression levels of miR-155 in 118 lymphoma patients' tissues, and Western blot was also used to analyze the expression level of proteins correlated with cell cycle and apoptosis in lymphoma cells. miR-155 expression levels were higher in lymphoma tissues compared with adjacent tissues. Downregulation of miR-155 inhibited lymphoma cell progress by arresting cell cycle in the G0/G1 phase and promoting apoptosis. Cell cycle-correlated proteins (cyclin B1, cyclin D1, and CDK4) were inhibited by downregulation of miR-155. Apoptosis-correlated proteins level (Bax/Bcl-2 and caspase 3 activity) were increased by downregulation of miR-155. In addition, a significant inverse correlation between the level of miR-155 and transforming growth factor-ß receptor 2 (TGFBR2) was observed, which has been demonstrated to be a novel tumor suppressor gene. A further in vivo tumor formation study in nude mice indicated that downregulation of miR-155 in lymphoma cells delayed the progress of tumor formation. These findings indicate that miR-155 may serve as a useful potential target for the treatment of lymphoma.
Assuntos
Apoptose/genética , Pontos de Checagem do Ciclo Celular/genética , Regulação para Baixo/genética , Linfoma Difuso de Grandes Células B/genética , MicroRNAs/genética , Animais , Proteínas Reguladoras de Apoptose/genética , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Fase G1/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fase de Repouso do Ciclo Celular/genéticaRESUMO
AIM: To investigate the combined diagnostic accuracy of acoustic radiation force impulse (ARFI), aspartate aminotransferase to platelet ratio index (APRI) and Forns index for a non-invasive assessment of liver fibrosis in patients with chronic hepatitis B (CHB). METHODS: In this prospective study, 206 patients had CHB with liver fibrosis stages F0-F4 classified by METAVIR and 40 were healthy volunteers were measured by ARFI, APRI and Forns index separately or combined as indicated. RESULTS: ARFI, APRI or Forns index demonstrated a significant correlation with the histological stage (all P < 0.001). According to the AUROC of ARFI and APRI for evaluating fibrotic stages more than F2, ARFI showed an enhanced diagnostic accuracy than APRI (P < 0.05). The combined measurement of ARFI and APRI exhibited better accuracy than ARFI alone when evaluating ≥ F2 fibrotic stage (Z = 2.77, P = 0.006). Combination of ARFI, APRI and Forns index did not obviously improve the diagnostic accuracy compared to the combination of ARFI and APRI (Z = 0.958, P = 0.338). CONCLUSION: ARFI + APRI showed enhanced diagnostic accuracy than ARFI or APRI alone for significant liver fibrosis and ARFI + APRI + Forns index shows the same effect with ARFI + APRI.
RESUMO
Genetic polymorphisms in human genes can influence the risk for HIV-1 infection and disease progression, although the reported effects of these alleles have been inconsistent. This review highlights the recent discoveries on global and Chinese genetic polymorphisms and their association with HIV-1 transmission and disease progression.
Assuntos
Infecções por HIV/epidemiologia , Infecções por HIV/genética , HIV-1 , Polimorfismo Genético , China/epidemiologia , HumanosRESUMO
OBJECTIVE: To investigate the imaging and pathological findings of severe pneumonia caused by human infected avian influenza (H7N9), and therefore to further understand and improve diagnostic accuracy of severe pneumonia caused by human infected avian influenza (H7N9). METHODS: The relevant clinical and imaging data of 19 cases, including 10 males and 9 females, with pneumonia caused by human infected avian influenza (H7N9) was retrospectively analyzed. One of the cases had received percutaneous lung biopsy, with the clinical, imaging and pathological changes possible to be analyzed. RESULTS: The lesions were mainly located at lower lobes and dorsal of lungs, involving multiple lobes and segments. Ground-glass opacities and/or pulmonary opacities were the more often imaging manifestations of severe pneumonia caused by human infected avian influenza (H7N9) in early and evolving phases (19/19,100%). By biopsy following percutaneous lung puncture, exudation of slurry, cellulose, RBC and neutrophils, formation of hyaline membrane, squamous metaplasia and organizing exudates were observable at the alveolar space. Some of alveoli collapsed, and some responded to show compensatory emphysema. CONCLUSION: The imaging features of severe pneumonia caused by human infected avian influenza (H7N9) include obvious ground-glass opacity and pulmonary consolidation, mainly at lower lobes and dorsal of lungs, with rapid changes. The cross-analysis of imaging and pathology preliminary can elucidate the pathological mechanisms of ground-glass opacities and pulmonary consolidation of severe pneumonia. Such an intensive study is beneficial to prompt clinicians to observe and evaluate the progress of the disease. In addition, it is also in favor of managing the symptoms and reducing the mortality rate.
Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Antivirais/efeitos adversos , Hepatopatias/etiologia , Fígado/efeitos dos fármacos , Síndrome da Imunodeficiência Adquirida/complicações , Adulto , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Antivirais/administração & dosagem , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , China , Feminino , Humanos , Fígado/fisiopatologia , Hepatopatias/sangue , Hepatopatias/fisiopatologia , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVE: Lamivudine resistant HBV strains in Shenzhen were detected at multiple sites and in large amounts to understand further the distribution of lamivudine resistant mutants. METHODS: 552 Hepatitis B patients's sera were examined using genechip method. Among them, 192 samples of lamivudine resistant mutant were further analyzed. RESULTS: In those 192 lamivudine resistant samples, 191 were YMDD mutants, 124 mutants of codon 528 and 9 mutants of codon 555. 88% YMDD mutants were multi-mutants of YVDD and codon 528; single mutants of YIDD; multi-mutants of YIDD and codon 528. 91% codon of YMDD mutants were GTG, ATT; the other 9% were ATA, ATC. CONCLUSIONS: These results suggest that mutants of codon 552 (YMDD) are core mutants. Mutants of codon 528 and 555 are incidental mutants, YVDD mutants always emerge with mutants of codon 528, but YIDD mutants appear differently. 9% YMDD mutants's codons are ATA or ATC. This may be the reason for the low positive rate shown by using the conventional PCR methods.
Assuntos
Resistência Microbiana a Medicamentos/genética , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Lamivudina/uso terapêutico , Mutação Puntual , Motivos de Aminoácidos , Antivirais/farmacologia , Antivirais/uso terapêutico , Códon/genética , DNA Polimerase Dirigida por DNA/genética , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/virologia , Humanos , Lamivudina/farmacologia , Análise de Sequência com Séries de OligonucleotídeosRESUMO
OBJECTIVE: To investigate a new therapy for effectively correcting severe hypoxemia in patients with infectious diseases by infusion of oxygen-enriched liquid, in order to raise the partial pressure of blood oxygen without passing through pathologically damaged alveoli of such patients. METHODS: Intravenous drip with oxygen-enriched liquids was given to 6 cases suffering from severe acute respiratory syndrome (SARS), and 3 cases of acquired immune deficiency syndrome (AIDS) in the course of treatment for 1 to 5 days, 500-700 ml per day. RESULTS: For all the 9 SARS cases, their hypoxemia was gradually corrected to normal in 20 minutes' or 4 hours' intravenous drip with oxygen-enriched liquid. Respiratory rate decreased from 29-49 breath/min to 18-22 breath/min, heart rate decreased from 89-145 beats/min to 60-79 beats/min, two faint patients regained consciousness, hypoxemia was redressed, partial pressure of oxygen in artery increased from 56 mm Hg (1 mm Hg=0.133 kPa) to 87 mm Hg, saturation of oxygen increased from 0.89 to 0.96. CONCLUSION: Intravenous drip of the oxygen-enriched liquid effectively helped correct the hypoxemia of SARS and other infectious diseases cases by bypassing the diseased alveoli through which oxygen would not pass into the blood by conventional oxygen inhalation. This therapy of oxygen-enriched liquid infusion could be quite life-saving in the combined treatment for SARS and other infectious diseases.
Assuntos
Doenças Transmissíveis/terapia , Hipóxia/terapia , Oxigênio/uso terapêutico , Adolescente , Adulto , Feminino , Humanos , Bombas de Infusão , Masculino , Projetos Piloto , Síndrome Respiratória Aguda Grave/terapia , Resultado do TratamentoRESUMO
Hepatic angiosarcoma, also called Kupffer's sarcoma, is a malignant mesenchymal neoplasm of endothelial cells, represents less than two percent of all primary liver neoplasm. Hepatic angiosarcoma is an infrequent and difficult-to-diagnose disease, mostly discovered by chance. Because of its rapid progression and usually fatal outcome, early diagnosis is necessary and complete surgical resection is the key to improve prognosis, but the neoplasm is often disseminated at the time of diagnosis, making resection impossible. Rare cases of hepatic angiosarcoma have been reported in the literature. Here, we report a case of hepatic angiosarcoma with spleen, lungs, right atrium and spine infiltration. Contrast enhanced abdomen CT and MRI scans revealed multiple nodules in the liver and spleen with rich blood supply, at the same time many metastases were noticed at bilateral lungs, right atrium and spine. The lesions rapidly deteriorated during the 2 months following the exams. The diagnosis of hepatic angiosarcoma was made after an open biopsy.