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1.
AIDS Res Hum Retroviruses ; 35(7): 679-683, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30924679

RESUMO

Jiangsu province has severe HIV-1 epidemic in China. Suqian which is located in north of the province has limited HIV epidemic information. Therefore, this study aimed to characterize the epidemic details in the area. A total of 196 plasma samples were collected from treated HIV-1-positive cases and viral RNA was extracted. Then HIV partial pol genes (nucleotide 2147-3462 by using HXB2 as calibrator) were amplified and sequenced. Finally, 84 partial pol genes were successfully obtained. The subtyping results indicate that multiple HIV-1 subtypes are circulating in Suqian district. Thereinto, CRF01_AE has been the dominant stains here and belonged to multiple lineages of CRF01_AE identified in China previously. Moreover, there is a high level of HIV drug resistance. All these results suggest HIV-1 epidemic in Suqian is rather complex and more measures must be performed for prevention and intervention in the area.


Assuntos
Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/genética , Fármacos Anti-HIV/uso terapêutico , Sequência de Bases , China/epidemiologia , Farmacorresistência Viral/efeitos dos fármacos , Farmacorresistência Viral/genética , Feminino , Genes pol/genética , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , HIV-1/classificação , HIV-1/efeitos dos fármacos , HIV-1/isolamento & purificação , Humanos , Masculino , Epidemiologia Molecular , Filogenia , RNA Viral/sangue , RNA Viral/genética
2.
J Med Virol ; 90(1): 93-100, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28851115

RESUMO

We aimed to explore whether maternal chronic hepatitis B virus (HBV) infection certainly affects preterm labor (birth) in pregnant women. Four databases were systematically searched up to May 31, 2017, without language restriction. Any study was included if it clearly defined exposure to chronic HBV infection, reported risk of preterm labor or birth in pregnant women, and reported relative risks (RRs) or odds ratios (ORs) or provided data for estimation. RRs (or ORs) with 95% confidence intervals were pooled using random-effects models. Statistical heterogeneity was assessed with Cochran's Q statistic and I2 statistic. Twenty-two observational studies involving 6 141 146 pregnant women (three prospective cohort studies, n = 1 116 799; 15 retrospective cohort studies, n = 5 022 513 and four case-control studies, n = 1834) were included. The risk of preterm labor was significantly intensified with chronic HBV infection compared with uninfected women, with substantial heterogeneity. Chronic HBV infection was also significantly associated with a 16% increase in the risk of preterm birth, with substantial heterogeneity. The risk of preterm birth significantly increased by 21% in HBsAg+/HBeAg+ pregnant women compared with uninfected pregnant women. Chronic HBV infection intensifies the risk of preterm labor and birth in pregnant women, but this conclusion should be interpreted with caution given the possibility of residual confounding and be confirmed by well-designed studies in the future.


Assuntos
Hepatite B Crônica/complicações , Trabalho de Parto Prematuro/etiologia , Complicações Infecciosas na Gravidez , Nascimento Prematuro/etiologia , Adulto , Estudos de Casos e Controles , Bases de Dados Factuais , Feminino , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/virologia , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Estudos Observacionais como Assunto , Trabalho de Parto Prematuro/epidemiologia , Trabalho de Parto Prematuro/virologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , Estudos Prospectivos , Estudos Retrospectivos
3.
Steroids ; 128: 89-94, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28899726

RESUMO

The efficacy, safety and health-economic outcomes were compared between corticosteroid and non-corticosteroid treatments in acute gout patients. All electronic literatures comparing the curative effects or full economic evaluations of corticosteroids versus non-corticosteroids on acute pain in acute gout patients and published until June 30, 2017 in any language were searched through PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. Pooled odds ratios with 95% confidence intervals and standard(or weighted) mean difference were calculated using random-or fixed-effects models according to the I2 statistic test of heterogeneity. Economic elevations were combined through qualitative narrative synthesis. Finally, seven randomized controlled trials(RCTs) involving 929 patients were included here and suggested corticosteroids had comparable analgesic efficacy to non-corticosteroids on day 5. As for inflammation and PGA, corticosteroids might outperform non-corticosteroids in reducing tenderness and swelling. Corticosteroids versus non-corticosteroids could significantly reduce incidence of only serious adverse advents, but not total adverse advents, with substantial heterogeneity. Qualitative narrative synthesis of economic elevation involving only one study shows corticosteroids are more cost-effective than indomethacin. The existing RCTs do not provide sufficient or precise evidence that corticosteroids are superior to non-corticosteroids in pain relief of acute gout patients. Therefore, studies on chronic use of corticosteroids or comparative studies with colchicine, tramadol and/or opiates may be needed in the future, as is patient satisfaction with analgesic control.


Assuntos
Corticosteroides/uso terapêutico , Análise Custo-Benefício , Gota/tratamento farmacológico , Inflamação/tratamento farmacológico , Corticosteroides/economia , Gota/economia , Humanos , Indometacina/economia , Indometacina/uso terapêutico , Inflamação/economia
4.
Clin Res Hepatol Gastroenterol ; 41(5): 533-542, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28866088

RESUMO

BACKGROUND/OBJECTIVES: Liver cirrhosis and its complications are important factors contributing to mortality worldwide. Statin use is probably associated with lower risk of hepatic decompensation and mortality, but not with cirrhosis or fibrosis progression according to a recent systematic review. We aimed to evaluate the definite effects of statins on the risk of virus-related cirrhosis. METHODS: We systematically searched four databases up to May 7, 2017, without language restriction. Studies were included if they evaluated and clearly defined exposure to statins, reported fibrosis progression, risk of cirrhosis in patients with chronic viral hepatitis or decompensation in cirrhotic patients, and reported relative risks (RRs) or odds ratios (ORs), or provided data for their estimation. Pooled RRs (or ORs) with 95% confidence intervals were calculated using the random-effects models irrespective of statistical heterogeneity assessed with the Cochran's Q statistic and I2 statistic. RESULTS: Ten observational studies involving 12,3445 patients (8 cohort studies, n=12,1823; 1 nested case-control, n=1350; and 1 abstract, n=272) were included. Statin use was associated with a statistically significant 51% reduction in the risk of virus-related cirrhosis (pooled RRs, 0.49; 95% CI, 0.30-0.80; P=0.004), with substantial heterogeneity (I2=98.3%; P<0.001). Statin use was also associated with a 51% reduction in the risk of decompensation (pooled RRs, 0.49; 95% CI, 0.41-0.59; P<0.001), which was statistically significant, with no heterogeneity (I2=33.8%; P=0.210). CONCLUSIONS: The meta-analysis showed that statin use was associated with a significantly reduced risk of virus-related cirrhosis and decompensation. However, these results should be interpreted with caution given the possibility of residual confounding. Large randomized controlled trials are warranted in future studies.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/virologia , Humanos
5.
Immunol Res ; 65(3): 739-749, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28286920

RESUMO

Liver injury after experimental acetaminophen treatment is mediated both by direct hepatocyte injury through a P450-generated toxic metabolite and indirectly by activated liver Kupffer cells and neutrophils. This study was designed to investigate the role of Notch signaling in the regulation of innate immune responses in acetaminophen (APAP)-induced liver injury. Using a mouse model of APAP-induced liver injury, wild-type (WT) and toll-like receptor 4 knockout (TLR4 KO) mice were injected intraperitoneally with APAP or PBS. Some animals were injected with γ-secretase inhibitor DAPT or DMSO vehicle. For the in vitro study, bone marrow-derived macrophages (BMMs) were transfected with Notch1 siRNA, TLR4 siRNA, and non-specific (NS) siRNA and stimulated with LPS. Indeed, paracetamol/acetaminophen-induced liver damage was worse after Notch blockade with DAPT in wild-type mice, which was accompanied by significantly increased ALT levels, diminished hairy and enhancer of split-1 (Hes1), and phosphorylated Stat3 and Akt but enhanced high mobility group box 1 (HMGB1), TLR4, NF-κB, and NLRP3 activation after APAP challenge. Mice receiving DAPT increased macrophage and neutrophil accumulation and hepatocellular apoptosis. However, TLR4 KO mice that received DAPT reduced APAP-induced liver damage and NF-κB, NLRP3, and cleaved caspase-1 activation. BMMs transfected with Notch1 siRNA reduced Hes1 and phosphorylated Stat3 and Akt but augmented HMGB1, TLR4, NF-κB, and NLRP3. Furthermore, TLR4 siRNA knockdown resulted in decreased NF-κB and NLRP3 and cleaved caspase-1 and IL-1ß levels following LPS stimulation. These results demonstrate that Notch signaling regulates innate NLRP3 inflammasome activation through regulation of HMGB1/TLR4/NF-κB activation in APAP-induced liver injury. Our novel findings underscore the critical role of the Notch1-Hes1 signaling cascade in the regulation of innate immunity in APAP-triggered liver inflammation. This might imply a novel therapeutic potential for the drug-induced damage-associated lethal hepatitis.


Assuntos
Acetaminofen/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Hepatócitos/fisiologia , Macrófagos/fisiologia , Receptor Notch1/metabolismo , Fatores de Transcrição HES-1/metabolismo , Acetaminofen/uso terapêutico , Animais , Células Cultivadas , Modelos Animais de Doenças , Proteína HMGB1/metabolismo , Hepatócitos/efeitos dos fármacos , Humanos , Imunidade Inata , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , RNA Interferente Pequeno/genética , Receptor Notch1/genética , Transdução de Sinais , Receptor 4 Toll-Like/genética
6.
BMC Infect Dis ; 16: 337, 2016 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-27450424

RESUMO

BACKGROUND: Mucormycosis is a kind of rare opportunistic fungal disease and the incidence of which has gradually increased. Disseminated mucormycosis (DM) is a life-threatening infection that mostly occurs in immunocompromised patients. The lung and brain are usually involved in disseminated mucormycosis, and other sites are scare. We report the first case of disseminated mucormycosis whose infection sites included lung, skin, liver, vertebra, and spinal cord that ensued after a right lung pneumonectomy in an immunocompetent patient. CASE PRESENTATION: A 20-year-old female underwent a right lung pneumonectomy for "lung cancer" presented with an intermittent fever for two years. A computed tomography (CT) scan showed an enclosed outstanding mass in the right chest wall. The patient also suffered from lower limb numbness and weakness, difficulty walking, and dysuria. Medical examination showed superficial feeling of the abdominal wall was decreased from the T7 and T8 level; muscle strength for both lower limbs was decreased; muscle tension of both lower limbs was also diminished. A biopsy through the right chest wall mass and thoracic mass by fistula of chest wall showed broad nonseptate hyphae with right-angle branching, consistent with mucormycosis. With titration of amphotericin B and its lipid complex, the patient recovered. CONCLUSIONS: Our case showed an unusual clinical presentation of disseminated mucormycosisin an immunocompetent patient.


Assuntos
Mucormicose/diagnóstico , Infecções Oportunistas/diagnóstico , Pneumonectomia/efeitos adversos , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/microbiologia , Osso e Ossos/patologia , Feminino , Humanos , Imunocompetência , Fígado/diagnóstico por imagem , Fígado/microbiologia , Fígado/patologia , Pulmão/diagnóstico por imagem , Pulmão/microbiologia , Pulmão/patologia , Pulmão/cirurgia , Mucormicose/microbiologia , Infecções Oportunistas/tratamento farmacológico , Pele/diagnóstico por imagem , Pele/microbiologia , Pele/patologia , Medula Espinal/diagnóstico por imagem , Medula Espinal/microbiologia , Medula Espinal/patologia , Tomografia Computadorizada por Raios X , Adulto Jovem
7.
Biomed Pharmacother ; 69: 277-84, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25661370

RESUMO

Cancer cells consume large amounts of glucose to produce lactate, even in the presence of ample oxygen. This phenomenon is known as the Warburg effect. The pyruvate kinase promotes aerobic glycolysis, and the pyruvate kinase M2 isoform (PKM2) is highly expressed in many cancer cells. Although the Warburg effect is a hallmark of cancer, the mechanism by which PKM2 contributes to the Warburg effect, and its role in tumor growth remain to be defined. We proposed that PKM2 activates transcription of hypoxia inducible factor-1α (HIF-1α) by phosphorylating STAT3 (signal transducer and activator of transcription 3) at Y705 (tyrosine 705) as a plausible mechanism for liver cancer cell proliferation. In the current study, we observed that PKM2 was over-expressed in hepatocellular carcinoma (HCC) tissues compared to adjacent normal tissues. The experiments further indicate that nuclear PKM2 is an active protein kinase in cultured cells. Knockdown of PKM2 affected the levels of HIF-1α and Bcl-xL (B-cell lymphoma-extra large), suggesting that PKM2 plays an important role in promoting cell proliferation. In conclusion, the current findings demonstrate that PKM2 is an active protein kinase, and promotes liver cancer cell proliferation by up-regulating HIF-1α and Bcl-xL expression.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/patologia , Piruvato Quinase/metabolismo , Regulação para Cima , Proteína bcl-X/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Núcleo Celular/metabolismo , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Hepáticas/genética , Masculino , Pessoa de Meia-Idade , Fosforilação , Fosfotirosina/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição RelA/metabolismo , Transcrição Genética , Células Tumorais Cultivadas , Adulto Jovem , Proteína bcl-X/metabolismo
8.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 29(6): 637-40, 2013 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-23746250

RESUMO

OBJECTIVE: To explore the effect of peripheral blood T lymphocyte activation on the blood cells, tissue injury and the development of disease in patients with severe fever with thrombocytopenia syndrome (SFTS). METHODS: The expressions of CD69, HLA-DR, CD28 and CTLA-4 on peripheral blood T lymphocytes were determined dynamically by flow cytometry and the relationships between the above immune molecules and ALT, AST, leukocytes, platelets were analyzed respectively. RESULTS: The expressions of CD69 and HLA-DR on peripheral blood T lymphocytes in patients with SFTS were elevated significantly during the whole course of disease (P<0.05). CD28 expression on CD4(+); lymphocyte subset decreased in the early stage and gradually increased to the normal range. Meanwhile, CTLA-4 expression on T lymphocytes went up in the late stage of viral infection. The levels of serum ALT, AST, LDH and CK were significantly higher than the upper limit of the normal and the counts of WBC and PLT dropped to the lowest at the outset. But all of them returned back to the normal range gradually with the down-regulation of CD69 and HLA-DR and the up-regulation of CTLA-4 on T lymphocyte. CONCLUSION: The overactivation of T lymphocytes may contribute to tissue injury and the high expression of CTLA-4 may be a negative feedback regulation to the overactivation of T lymphocytes, which plays an important role in immunoregulation of SFTS patients.


Assuntos
Ativação Linfocitária/imunologia , Febre por Flebótomos/imunologia , Linfócitos T/imunologia , Adulto , Idoso , Plaquetas/imunologia , Plaquetas/metabolismo , Antígenos CD28/metabolismo , Antígenos CD4/metabolismo , Antígenos CD8/metabolismo , Antígeno CTLA-4/metabolismo , Feminino , Humanos , Leucócitos/imunologia , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Febre por Flebótomos/metabolismo , Prognóstico , Linfócitos T/metabolismo , Fatores de Tempo
9.
Zhonghua Gan Zang Bing Za Zhi ; 19(1): 38-43, 2011 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-21272457

RESUMO

This report aims to investigate the dynamical changes of HBcAg18-27 epitope specific cytotoxic T lymphocytes(CTL), alanine aminotransferase (ALT), HBV DNA and HBsAg in peripheral blood of acute hepatitis B patients, and to explore the roles of HBcAg18-27-specific CTLs in virus clearance and liver injury. Acute hepatitis B (AHB) and chronic hepatitis B (CHB) patients were divided into two groups according to results of HLA-A0201. Patients with positive HLA-A0201 were classified into HBcAg-specific CTL group and those with negative HLA-A0201 were referred as control group. The specific CTLs were stained with HLA-A0201 limited HBcAg18-27 epitope MHC-Pentamer and the frequencies of CTLs, T, B, NK and NKT cells were detected by flow cytometry (FCM). The serum ALT, HBV DNA and HBsAg were examined using speed analysis, quantitative PCR and abbott chemiluminescent technology. The frequencies of HBcAg18-27-specific CTLs in AHB patients were higher in the early three weeks as compared to the late three weeks. The apex time of HBV-specific CTL frequencies lagged behind those of HBV DNA, HBsAg and ALT. The loss of HBsAg in patients with high frequencies of HBV-specific CTL was earlier than that in patients with low frequencies (t = 2.018, P value is less than 0.05). In the second week the peak frequencies of CD3+CD8+ cells overlapped with that of HBcAg18-27-specific CTLs and with a positive correlation between (r = 0.420, P value is less than 0.05). During the early stages of AHB, the frequencies of NK and NKT cells were found significantly lower than that of control group and CHB group and the levels were back to normal after recovery. Moreover, a negative correlation existed between the frequencies of NK cells and the dynamic changes of HBcAg18-27-specific CTLs (r = -0.435, P value is less than 0.01) in AHB group. The frequencies of HBcAg18-27-specific CTLs were significantly higher as compared to CHB group in the first three weeks (z = -3.258, -4.04, and -3.259, P value is less than 0.01). The early loss of HBsAg was closely related to the high frequencies of HBcAg18-27 specific CTLs in AHB patients. HBcAg-specific CTL frequencies in peripheral blood could be used to predict clinical outcome after HBV infection. The frequencies of CD8+ T cells can reflect the changes of frequencies of HBcAg-specific CTL during acute HBV infection.


Assuntos
Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Hepatite B/imunologia , Linfócitos T Citotóxicos/imunologia , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Antígeno HLA-A2/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Humanos , Células Matadoras Naturais/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Linfócitos T Citotóxicos/citologia , Adulto Jovem
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