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1.
Future Oncol ; 20(3): 121-129, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38353107

RESUMO

Immune checkpoint inhibitors (ICIs) plus chemotherapy has demonstrated efficacy in resectable non-small-cell lung cancer (NSCLC), yet the optimal period of neoadjuvant immunochemotherapy is undetermined. In a phase II study (neoSCORE, NCT04459611), more neoadjuvant therapy cycles appeared to provide greater pathological remission, and patients with squamous NSCLC had a better major pathological response rate than those with nonsquamous NSCLC. Sintilimab, a monoclonal anti-PD-1 antibody, has shown encouraging antitumor activity and safety in multiple cancers, including NSCLC. Here, we describe the study design of neoSCORE II (NCT05429463), a randomized, open-label, multicenter phase III trial comparing the efficacy and safety of three cycles with four cycles of neoadjuvant sintilimab plus platinum-based chemotherapy in resectable stage IIA-IIIB squamous NSCLC. Trial registration number: NCT05429463 (ClinicalTrials.gov).


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Terapia Neoadjuvante , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase II como Assunto
2.
Mycopathologia ; 182(7-8): 751-754, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28349349

RESUMO

Talaromyces marneffei (also called Penicilliosis Marneffei or T. marneffei) is a rare fungal disease that is prevalent mainly in Southeast Asia and commonly seen in immunocompromised hosts. It was rarely observed in immunocompetent hosts. We report a case of acute disseminated T. marneffei in an immunocompetent patient in the non-prevalent region. This patient had never visited the endemic area. The patient experienced a persistent fever. Brain CT and magnetic resonance imaging (MRI) showed a mass in the right frontal with osteolytic damage. Excessive white blood cell (WBC) count and C-reactive protein content were observed. Antibiotics including meropenem and linezolid could not play an effect, and another two hard masses appeared in his right neck and front chest wall. The aspirates from the right frontal mass and bone marrow were cultured. The final diagnose of this infection was disseminated T. marneffei. After voriconazole treatment, all symptoms improved gradually. We present this case and aim to promote more clinicians and microbiologists in the non-endemic region to recognize this rare disease.


Assuntos
Fungemia/diagnóstico , Fungemia/patologia , Talaromyces/isolamento & purificação , Antifúngicos/uso terapêutico , Ásia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Proteína C-Reativa/análise , Fungemia/microbiologia , Humanos , Contagem de Leucócitos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Pescoço/patologia , Parede Torácica/patologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Voriconazol/uso terapêutico
3.
Arch Virol ; 161(5): 1239-59, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26887968

RESUMO

A novel avian influenza A (H7N9) virus caused 5-10 % mild and 30.5 % fatal human infections as of December 10, 2015. In order to investigate the reason for the higher rate of fatal outcome of this infection, this study compared the molecular epidemiology and virology of avian influenza A (H7N9) viruses from mild (N = 14), severe (N = 50) and fatal (N = 35) cases, as well as from non-human hosts (N = 73). The epidemiological results showed that the average age of the people in the mild, severe and fatal groups was 27.6, 52 and 62 years old, respectively (p < 0.001). Males accounted for 42.9 % (6/14), 58.0 % (29/50), and 74.3 % (26/35) of cases in the mild, severe and fatal group respectively (p = 0.094). Median days from onset to start of antiviral treatment were 2, 5 and 7 days in the mild, severe and fatal group, respectively (p = 0.002). The median time from onset to discharge/death was 12, 40 and 19 days in the mild, severe and fatal group, respectively (p < 0.001). Analysis of whole genome sequences showed that PB2 (E627K), NA (R294K) and PA (V100A) mutations were markedly associated with an increased fatality rate, while HA (N276D) and PB2 (N559T) mutations were clearly related to mild cases. There were no differences in the genotypes, adaptation to mammalian hosts, and genetic identity between the three types of infection. In conclusion, advanced age and delayed confirmation of diagnosis and antiviral intervention were risk factors for death. Furthermore, PB2 (E627K), NA (R294K) and PA (V100A) mutations might contribute to a fatal outcome in human H7N9 infection.


Assuntos
Subtipo H7N9 do Vírus da Influenza A , Influenza Humana/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Subtipo H7N9 do Vírus da Influenza A/genética , Subtipo H7N9 do Vírus da Influenza A/patogenicidade , Influenza Humana/mortalidade , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Filogenia , RNA Viral/genética , Índice de Gravidade de Doença , Adulto Jovem
4.
J Asthma ; 51(5): 451-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24467722

RESUMO

OBJECTIVE: Bronchial asthma is a chronic inflammatory disease of the airway mediated by a Th2 immune response. A great deal of data has demonstrated that regulatory T cells (Tregs) have the ability to suppress Th2 immune responses and the transcription factor fork-head box protein 3 (Foxp3) is indispensable for the development of CD4 + CD25 + Tregs. In this study, we hypothesized that enhanced local Foxp3 expression in lung tissue could suppress Th2-mediated allergic asthma. METHODS: Foxp3/PMX retroviruses containing the mouse Foxp3 gene were constructed and administered into asthmatic mice through intra-tracheal instillation before ovalbumin challenging. Foxp3 expression, airway hyper-responsiveness (AHR), bronchoalveolar lavage fluid (BALF) and tissue inflammatory cell and cytokine profiles were characterized. RESULTS: Foxp3 mRNA and protein were increased in the lung tissue of asthmatic mice. Enhanced expression of Foxp3 locally in the lung tissue reduced the airway AHR, inflammatory cell infiltration and mucus production. It also attenuated Th2 and Th17 immune responses as evidenced by reduced IL-4, IL-13 and IL-17 levels. CONCLUSIONS: This study demonstrates that enhanced Foxp3 expression in the airway by intra-tracheally instilled Foxp3/PMX retroviruses alleviates allergic airway inflammation by reducing the Th2 immune response.


Assuntos
Asma/genética , Fatores de Transcrição Forkhead/genética , Regulação da Expressão Gênica , Animais , Asma/metabolismo , Asma/prevenção & controle , Modelos Animais de Doenças , Feminino , Fatores de Transcrição Forkhead/biossíntese , Inflamação/genética , Inflamação/metabolismo , Inflamação/prevenção & controle , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos BALB C
5.
Respir Res ; 9: 16, 2008 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-18237405

RESUMO

BACKGROUND: Nontypeable Haemophilus influenzae (NTHi) is an important respiratory pathogen implicated as an infectious trigger in chronic obstructive pulmonary disease, but its molecular interaction with human lung epithelial cells remains unclear. Herein, we tested that the hypothesis that NTHi induces the expression of cyclooxygenase (COX)-2 and prostaglandin E2 (PGE2) via activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappa B in pulmonary alveolar epithelial cells. METHODS: Human alveolar epithelial A549 cells were infected with different concentrations of NTHi. The phosphorylation of p38 MAPK was detected by Western blot analysis, the DNA binding activity of NF-kappa B was assessed by electrophoretic mobility shift assay (EMSA), and the expressions of COX-1 and 2 mRNA and PGE2 protein were measured by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA), respectively. The roles of Toll-like receptor (TLR) 2 and TLR4, well known NTHi recognizing receptor in lung epithelial cell and gram-negative bacteria receptor, respectively, on the NTHi-induced COX-2 expression were investigated in the HEK293 cells overexpressing TLR2 and TLR4 in vitro and in the mouse model of NTHi-induced pneumonia by using TLR2 and TLR4 knock-out mice in vivo. In addition, the role of p38 MAPK and NF-kappa B on the NTHi-induced COX-2 and PGE2 expression was investigated by using their specific chemical inhibitors. RESULTS: NTHi induced COX-2 mRNA expression in a dose-dependent manner, but not COX-1 mRNA expression in A549 cells. The enhanced expression of PGE2 by NTHi infection was significantly decreased by pre-treatment of COX-2 specific inhibitor, but not by COX-1 inhibitor. NTHi induced COX-2 expression was mediated by TLR2 in the epithelial cell in vitro and in the lungs of mice in vivo. NTHi induced phosphorylation of p38 MAPK and up-regulated DNA binding activity of NF-kappa B. Moreover, the expressions of COX-2 and PGE2 were significantly inhibited by specific inhibitors of p38 MAPK and NF-kappa B. However, NTHi-induced DNA binding activity of NF-kappa B was not affected by the inhibition of p38 MAPK. CONCLUSION: NTHi induces COX-2 and PGE2 expression in a p38 MAPK and NF-kappa B-dependent manner through TLR2 in lung epithelial cells in vitro and lung tissues in vivo. The full understanding of the role of endogenous anti-inflammatory PGE2 and its regulation will bring new insight to the resolution of inflammation in pulmonary bacterial infections.


Assuntos
Ciclo-Oxigenase 2/biossíntese , Dinoprostona/biossíntese , Células Epiteliais/imunologia , Infecções por Haemophilus/imunologia , NF-kappa B/metabolismo , Alvéolos Pulmonares/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Linhagem Celular , Indução Enzimática/imunologia , Regulação da Expressão Gênica , Haemophilus influenzae/isolamento & purificação , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Animais , Fosforilação , Pneumonia Bacteriana/imunologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
7.
Artigo em Inglês | MEDLINE | ID: mdl-28273867

RESUMO

This study aimed to assess the mortality risks for human infection with high (HPAI) and low (LPAI) pathogenicity avian influenza viruses. The HPAI case fatality rate (CFR) was far higher than the LPAI CFR [66.0% (293/444) vs. 68.75% (11/16) vs. 40.4% (265/656) vs. 0.0% (0/18) in the cases with H5N1, H5N6, H7N9, and H9N2 viruses, respectively; p < 0.001]. Similarly, the CFR of the index cases was greater than the secondary cases with H5N1 [100% (43/43) vs. 43.3% (42/97), p < 0.001]. Old age [22.5 vs. 17 years for H5N1, p = 0.018; 61 vs. 49 years for H7H9, p < 0.001], concurrent diseases [18.8% (15/80) vs. 8.33% (9/108) for H5N1, p = 0.046; 58.6% (156/266) vs. 34.8% (135/388) for H7H9, p < 0.001], delayed confirmation [13 vs. 6 days for H5N1, p < 0.001; 10 vs. 8 days for H7N9, p = 0.011] in the fatalities and survivors, were risk factors for deaths. With regard to the H5N1 clusters, exposure to poultry [67.4% (29/43) vs. 45.2% (19/42), p = 0.039] was the higher risk for the primary than the secondary deaths. In conclusion, old age, comorbidities, delayed confirmation, along with poultry exposure are the major risks contributing to fatal outcomes in human HPAI and LPAI infections.


Assuntos
Virus da Influenza A Subtipo H5N1/patogenicidade , Subtipo H7N9 do Vírus da Influenza A/patogenicidade , Vírus da Influenza A Subtipo H9N2/patogenicidade , Influenza Aviária/virologia , Influenza Humana/epidemiologia , Influenza Humana/virologia , Adolescente , Animais , Aves , Feminino , Humanos , Incidência , Influenza Aviária/epidemiologia , Influenza Humana/mortalidade , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estações do Ano , Virulência , Adulto Jovem
8.
Int J Infect Dis ; 49: 9-17, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27235087

RESUMO

BACKGROUND: Previous research has suggested that avian influenza A H7N9 has a greater potential pandemic risk than influenza A H5N1. This research investigated the difference in human clustered and sporadic cases of H7N9 virus and estimated the relative risk of clustered infections. METHODS: Comparative epidemiology and virology studies were performed among 72 sporadic confirmed cases, 17 family clusters (FCs) caused by human-to-human transmission, and eight live bird market clusters (LCs) caused by co-exposure to the poultry environment. RESULTS: The case fatality of FCs, LCs and sporadic cases (36%, 26%, and 29%, respectively) did not differ among the three groups (p>0.05). The average age (36 years, 60 years, and 58 years), co-morbidities (31%, 60%, and 54%), exposure to birds (72%, 100%, and 83%), and H7N9-positive rate (20%, 64%, and 35%) in FCs, LCs, and sporadic cases, respectively, differed significantly (p<0.05). These higher risks were associated with increased mortality. There was no difference between primary and secondary cases in LCs (p>0.05). However, exposure to a person with confirmed avian influenza A H7N9 (primary 12% vs. secondary 95%), history of visiting a live bird market (100% vs. 59%), multiple exposures (live bird exposure and human-to-human transmission history) (12% vs. 55%), and median days from onset to antiviral treatment (6 days vs. 3 days) differed significantly between primary and secondary cases in FCs (p<0.05). Mild cases were found in 6% of primary cases vs. 32% of secondary cases in FCs (p<0.05). Twenty-five isolates from the three groups showed 99.1-99.9% homology and increased human adaptation. CONCLUSIONS: There was no statistical difference in the case fatality rate and limited transmission between FCs and LCs. However, the severity of the primary cases in FCs was much higher than that of the secondary cases due to the older age and greater underlying disease of the latter patients.


Assuntos
Subtipo H7N9 do Vírus da Influenza A/isolamento & purificação , Influenza Aviária/transmissão , Influenza Humana/transmissão , Adulto , Animais , China/epidemiologia , Feminino , Humanos , Subtipo H7N9 do Vírus da Influenza A/fisiologia , Influenza Aviária/epidemiologia , Influenza Aviária/virologia , Influenza Humana/epidemiologia , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Aves Domésticas , Adulto Jovem
9.
Artigo em Chinês | MEDLINE | ID: mdl-15748514

RESUMO

OBJECTIVE: In order to study the pathogenesis of latex allergy and the significance in the prevention and cure of occupational diseases. METHODS: 651 cases in the out-patient department were tested with skin prick test (SPT), and the specific IgE (sIgE) to latex were detected by means of disk ELISA and Western-blot. RESULTS: It was found that the positive rate of latex SPT (37.5%) and sIgE (31.25%) were rather higher in patients in comparison with those of the normal. The positive rate of latex sIgE was much higher in the high-risk group than that of the low-risk group and the normal. The serum of the patients can react with multi-bands in the latex glove extracts. CONCLUSION: The prevalence of latex allergy is rather high, this disease is mediated by IgE. The people in high-risk should be tested by latex allergy in order to take proper occupational and daily protection.


Assuntos
Hipersensibilidade ao Látex/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulina E/sangue , Lactente , Hipersensibilidade ao Látex/diagnóstico , Hipersensibilidade ao Látex/prevenção & controle , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/diagnóstico , Doenças Profissionais/etiologia , Doenças Profissionais/prevenção & controle , Pacientes Ambulatoriais , Testes Cutâneos , Adulto Jovem
10.
Int J Clin Exp Pathol ; 8(6): 7482-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26261657

RESUMO

Localized (primary) pulmonary amyloidosis associated with pulmonary low-grade B cell lymphoma is rarely occurred. Here we report an unusual case of nodular pulmonary amyloidosis and obvious ossification due to primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma with extensive plasmacytic differentiation in a 59-year-old man; moreover, two bronchial lymph nodes were involved histologically. The patient underwent a left lower lobectomy along with mediastinal lymphadenectomy. He received no adjuvant therapy and the postoperative course was uneventful within the 14 months follow-up period after his initial diagnosis.


Assuntos
Amiloidose/patologia , Neoplasias Pulmonares/patologia , Linfoma de Zona Marginal Tipo Células B/patologia , Ossificação Heterotópica/patologia , Plasmócitos/patologia , Amiloidose/etiologia , Biomarcadores Tumorais/análise , Diferenciação Celular , Humanos , Imuno-Histoquímica , Linfoma de Zona Marginal Tipo Células B/complicações , Masculino , Pessoa de Meia-Idade , Ossificação Heterotópica/etiologia
11.
Acta Pharmacol Sin ; 26(9): 1117-22, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16115380

RESUMO

AIM: To investigate effects of CpG oligodeoxynucleotide (CpG ODN) on the mRNA expression of transcription factors GATA binding protein 3 (GATA-3) and T-box expressed in T cells (T-bet) in asthmatic mice. METHODS: An asthmatic mouse model was established and treated with CpG ODN. Total inflammatory cells and eosinophils in bronchoalveolar lavage fluid (BALF) were counted and inflammatory cell infiltration in lung tissue was evaluated. Interferon-gamma and interleukin-4 concentrations in BALF and splenocyte culture supernatants were detected using an enzyme-linked immunosorbent assay. Transcription factor GATA-3 and T-bet mRNA expression in splenocytes and lung tissue were detected by reverse transcription-polymerase chain reaction. RESULTS: Total inflammatory cells and eosinophils in BALF were reduced in the CpG ODN-treated group compared with the asthma group, and inflammatory cell infiltration in lung tissue was also significantly alleviated. CpG ODN treatment increased the interferon-gamma concentration but decreased the interleukin-4 concentration in both BALF and splenocyte culture supernatants. GATA-3 mRNA expression was reduced in both lung tissue and splenocytes in the CpG ODN-treated group, while the mRNA ratio of T-bet to GATA-3 in splenocytes was increased. CONCLUSION: CpG ODN treatment inhibits airway inflammatory cell infiltration and regulates interferon-gamma/interleukin-4 synthesis in asthmatic mice, possibly through a mechanism of downregulation of GATA-3 mRNA expression in both lung tissue and splenocytes.


Assuntos
Asma/metabolismo , Fator de Transcrição GATA3/biossíntese , Oligodesoxirribonucleotídeos/farmacologia , Proteínas com Domínio T/biossíntese , Animais , Asma/patologia , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Eosinófilos/citologia , Eosinófilos/metabolismo , Fator de Transcrição GATA3/genética , Interferon gama/metabolismo , Interleucina-4/metabolismo , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , RNA Mensageiro/biossíntese , Baço/citologia , Baço/metabolismo , Proteínas com Domínio T/genética , Linfócitos T/metabolismo
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