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BACKGROUND: To investigate the CT imaging features and microbial phenotypes of primary severe community-acquired pneumonia caused by hypervirulent Klebsiella pneumoniae (hvKp). METHODS: Patients diagnosed with primary hvKp pneumonia were included, and their clinical data were analyzed, including the baseline characteristics and CT imaging results. After hypermucoviscosity phenotyping, the strains, serological types, and virulence genes of hvKp were identified using multiplex PCR. RESULTS: Twelve patients with primary hvKp pneumonia were included (11 males, 1 female). All patients were infected via respiratory tract inhalation. Ten patients were long-term drinkers. Four patients (33.3%), who were long-term alcohol abusers, died within 30 days after diagnosis. No extrapulmonary metastatic infection was found in any patient. The imaging of lung lesions at the early disease stage exhibited an extensive consolidation in the lungs. As the disease progressed, the most common imaging features were pleural effusion (9/12), cavitation and necrosis (8/12), and pneumothorax (3/12). The serological typing of the capsular polysaccharides on hvKp strains were K1 (6/12) and K2 (6/12). Furthermore, the virulence genotyping showed rmpA (11/12), magA (11/12), ureA (12/12), mrkD (12/12), fim-1 (12/12), wabG (12/12), ybtS (12/12), and iucB (11/12). CONCLUSIONS: Primary severe community-acquired hvKp-associated pneumonia is more common in men, especially those with a long-term history of alcohol consumption. CT scanning at the early disease stage mostly showed extensive pulmonary consolidation, which was prone to be combined with cavitation, necrosis, and pleural effusion. K1 and K2 serotypes were identified among the hvKp strains, which were not prone to form extrapulmonary metastasis via the bloodstream.
Assuntos
Infecções Comunitárias Adquiridas , Infecções por Klebsiella , Derrame Pleural , Pneumonia , Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/diagnóstico por imagem , Infecções Comunitárias Adquiridas/tratamento farmacológico , Feminino , Humanos , Infecções por Klebsiella/diagnóstico , Klebsiella pneumoniae/genética , Masculino , Tipagem de Sequências Multilocus , Necrose/tratamento farmacológico , Pneumonia/tratamento farmacológicoRESUMO
Long noncoding RNAs have been reported to be essential regulators in several human diseases, including tumorigenesis. A recent report revealed that FLVCR1-AS1 promotes the progression of hepatocellular carcinoma. However, whether FLVCR1-AS1 is involved in lung cancer remains unclear. In this study, we found that the expression of FLVCR1-AS1 was increased in lung cancer tissues according to The Cancer Genome Atlas database. Similarly, FLVCR1-AS1 was significantly upregulated in lung cancer cell lines. Knockdown of FLVCR1-AS1 dramatically reduced the cell proliferation, migration, and invasion of SPCA1 and A549. Mechanistically, we found that the expression levels of CTNNB1, SOX4, CCND1, CCND2, c-MYC, as well as nucleus ß-catenin were decreased in lung cancer cells after FLVCR1-AS1 silencing. Thus, FLVCR1-AS1 positively regulates the activation of the Wnt/ß-catenin pathway. Overexpression of CTNNB1 reversed the effect of FLVCR1-AS1 knockdown on A549 cells. In sum, FLVCR1-AS1 silencing inhibited the proliferation, migration, and invasion of lung cancer cells by inhibiting the activity of the Wnt/ß-catenin signaling pathway.
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Neoplasias Pulmonares/patologia , RNA Longo não Codificante/genética , Via de Sinalização Wnt/genética , Células A549 , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Ciclina D1/genética , Ciclina D1/metabolismo , Ciclina D2/genética , Ciclina D2/metabolismo , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , RNA Antissenso , Fatores de Transcrição SOXC/genética , Fatores de Transcrição SOXC/metabolismo , beta Catenina/genética , beta Catenina/metabolismoRESUMO
Photothermal therapy (PTT), which utilizes nanomaterials to harvest laser energy and convert it into heat to ablate tumor cells, has been rapidly developed for lung tumor treatment, but most of the PTT-related nanomaterials are not degradable, and the immune response associated with PTT is unclear, which leads to unsatisfactory results of the actual PTT. Herein, we rationally designed and prepared a manganese ion-doped polydopamine nanomaterial (MnPDA) for immune-activated PTT with high efficiency. Firstly, MnPDA exhibited 57.2% photothermal conversion efficiency to accomplish high-efficiency PTT, and secondly, MnPDA can be stimulated by glutathione (GSH) to the release of Mn2+, and it can produce ·OH in a Fenton-like reaction with the overexpressed H2O2 and stimulate the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. These two synergistically can effectively remove lung tumor cells that have not been ablated by PTT, resulting in an 86.7% tumor suppression rate under laser irradiation of MnPDA in vivo, and further significantly activated the downstream immune response, as evidenced by an increased ratio of cytotoxic T cells to immunosuppressive Treg cells. Conclusively, the GSH degradable MnPDA nanoparticles can be used for photothermal therapy and cGAS-STING-activated immunotherapy of lung tumors, which provides a new idea and strategy for the future treatment of lung tumors.
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Indóis , Neoplasias Pulmonares , Nanopartículas , Neoplasias , Polímeros , Humanos , Manganês , Peróxido de Hidrogênio , Terapia Fototérmica , Imunoterapia , Neoplasias Pulmonares/terapia , GlutationaRESUMO
Nocardia species usually cause opportunistic infections, and the frequency of these infections is increasing owing to the growing population of immunocompromised hosts. However, Nocardia may sometimes causes an infectious disease in immunocompetent hosts. Herein, we report two cases of pulmonary nocardiasis in immunocompetent individuals, whose chest computed tomography (CT) findings mimicked bronchiectasis. Samples of bronchalveolar lavage (BAL) fluid obtained by bronchoscopy showed filamentous, branching, gram-positive rods, acid-fast filamentous branching rods, and a colony of suspected Nocardia was cultured. Based on 16sRNA and hsp65 gene sequence analysis, case 1 was identified as N. cyriacigeorgica, but case 2 was not matched. The patients responded well to treatment with the combination of sulfamethoxazole and linezolid.
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Bronquiectasia/diagnóstico por imagem , Linezolida/uso terapêutico , Nocardiose/diagnóstico por imagem , Nocardiose/tratamento farmacológico , Sulfametoxazol/administração & dosagem , Tomografia Computadorizada por Raios X/métodos , Bronquiectasia/diagnóstico , Diagnóstico Diferencial , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Imunocompetência/imunologia , Masculino , Pessoa de Meia-Idade , Nocardia/efeitos dos fármacos , Nocardia/isolamento & purificação , Nocardiose/diagnóstico , Medição de Risco , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: The application of gene-loaded microbubbles (MBs) combined with ultrasound that results in increased delivery efficiency may be an excellent method of gene delivery. This study aimed to discuss the effects of ultrasound-MB-mediated microRNA (miR)-449a on lung cancer (LC) development by targeting Notch1. METHODS: Initially, miR-449a expression in LC tissues, paracancerous tissues, LC cell lines, and lung epithelial cells was detected and its association with LC patients' clinical characteristics was analyzed. The gain-of-function studies were performed to probe the roles of miR-449a and ultrasound-MB-mediated miR-449a in LC progression. Then, RT-qPCR combined with Western blot analysis was applied to verify the levels of miR-449a, Notch1, proliferation- and apoptosis-related proteins. Moreover, xenograft tumors in nude mice were also applied for in vivo experiments. RESULTS: Poorly expressed miR-449a was observed in LC, and its expression was associated with clinical staging, differentiation and lymph node metastasis of LC patients. Overexpression of miR-449a suppressed LC cell proliferation and promoted G2/M arrest and apoptosis. Ultrasound-MB-mediated miR-449a strengthened inhibitory effects of miR-449a on cell growth and resistance to apoptosis. miR-449a inhibited H1299 cell activity by targeting Notch1. CONCLUSION: Our data supported that miR-449a overexpression inhibited LC cell growth, and ultrasound-MB-mediated miR-449a reinforced the repressive effects of miR-449a on LC progression. This investigation may offer new insight for LC treatment.
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BACKGROUND: Droplet digital polymerase chain reaction (ddPCR) is an emerging technology for quantitative cell-free DNA oncology applications. However, a ddPCR assay for the epidermal growth factor receptor (EGFR) p.Thr790Met (T790M) mutation suitable for clinical use remains to be established with analytical and clinical validations. OBJECTIVE: We aimed to develop and validate a new ddPCR assay to quantify the T790M mutation in plasma for monitoring and predicting the progression of advanced non-small-cell lung cancer (NSCLC). METHODS: Specificity of the ddPCR assay was evaluated with genomic DNA samples from healthy individuals. The inter- and intraday variations of the assay were evaluated using mixtures of plasmid DNA containing wild-type EGFR and T790M mutation sequences. We assessed the clinical utility of the T790M assay in a multicenter prospective study in patients with advanced NSCLC receiving tyrosine kinase inhibitor (TKI) treatment by analyzing longitudinal plasma DNA samples. RESULTS: We set the criteria for a positive call when the following conditions were satisfied: (1) T790M mutation frequency > 0.098% (3 standard deviations above the background signal); (2) at least two positive droplets in duplicate ddPCR reactions. Among the 62 patients with advanced NSCLC exhibiting resistance to TKI treatment, 15 had one or more serial plasma samples that tested positive for T790M. T790M mutation was detected in the plasma as early as 205 days (median 95 days) before disease progression, determined by imaging analysis. Plasma T790M concentrations also correlated with intervention after disease progression. CONCLUSIONS: We developed a ddPCR assay to quantify the T790M mutation in plasma. Quantification of longitudinal plasma T790M mutation may allow noninvasive assessment of drug resistance and guide follow-up treatment in TKI-treated patients with NSCLC. TRIAL REGISTRATION: Clinical Trials.gov identifier: NCT02804100.
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Carcinoma Pulmonar de Células não Pequenas/enzimologia , Neoplasias Pulmonares/enzimologia , Mutação , Reação em Cadeia da Polimerase em Tempo Real/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/genética , Estudos de Casos e Controles , DNA/sangue , DNA/genética , Progressão da Doença , Receptores ErbB/sangue , Receptores ErbB/genética , Feminino , Humanos , Estudos Longitudinais , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos ProspectivosRESUMO
INTRODUCTION: This study aimed to investigate the prevalence, clinical and radiographic features, and antibiotic responses of Mycoplasma pneumoniae (M. pneumoniae) infections in hospitalized adults with community-acquired pneumonia (CAP) in China. METHODOLOGY: Serum specimens collected from 189 CAP patients in both acute phase and convalescence were tested for IgG, IgA, and IgM mixed antibodies specific to M. pneumoniae. The clinical and radiographic characteristics and efficacy of three antibiotic regimens were compared between patients with M. pneumoniae infection and those without. RESULTS: Among 189 CAP patients, 88 (46.6%) were positive for M. pneumoniae infection. Compared to the negative patients, patients with M. pneumoniae infection were significantly younger, had higher rates of dry cough, and had white blood cell counts of <1010/L, but had less purulent sputum. Radiography further showed more centrilobular nodules, ground-glass opacities, tree-in-bud patterns and thickened bronchovascular bundles, but less pleural effusion and larger tracts of real opacities in patients with M. pneumoniae infections. Among the three regimens used, patients with moxifloxacin required significantly shorter fever abatement, treatment, and hospitalization times than those with azithromycin plus ceftriaxone and ceftriaxone only. CONCLUSIONS: M. pneumoniae infection was present in almost half of the CAP population in east China, with some distinct clinical and radiographic features. Moxifloxacin was an effective antibiotic for this infection.