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OBJECTIVES: Lung adenocarcinoma (LUAD) is a malignant tumor originating from the bronchial mucosa or glands of the lung, with the fastest increasing morbidity and mortality. Therefore, the prognosis of lung cancer remains poor. Glycerol-3-phosphate dehydrogenase 2 (GPD2) is a widely existing protein pattern sequence in biology and is closely related to tumor progression. The therapy values of GPD2 inhibitor in LUAD were unclear. Therefore, we aimed to analyze the therapy values of GPD2 inhibitor in LUAD. MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA)-LUAD database was used to analyze the expression levels of GPD2 in LUAD tissues. The relationship between GPD2 expression and LUAD patient survival was analyzed by Kaplan-Meier method. Moreover, KM04416 as a target inhibitor of GPD2 was used to further investigate the therapy value of GPD2 inhibitor in LUAD cells lines (A549 cell and H1299 cell). The TISIDB website was used to investigate the associations between GPD2 expression and immune cell infiltration in LUAD. RESULTS: The results showed that GPD2 is overexpressed in LUAD tissues and significantly associated with poor survival. KM04416 can suppress the progression of LUAD cells by targeting GPD2. Low expression of GPD2 is related to high infiltration of immune cells. CONCLUSIONS: In summary, our present study found that targeting inhibition of GPD2 by KM04416 can suppress LUAD progression via adjusting immune cell infiltration.
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Adenocarcinoma de Pulmão , Progressão da Doença , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Prognóstico , Regulação Neoplásica da Expressão GênicaRESUMO
Background: Liver dysfunction was common in coronavirus disease 2019 (COVID-19), but its association with clinical features and poor prognosis has not been fully delineated. Our study aimed to determine the role of liver dysfunction in COVID-19 and understand the predictors for worse outcomes in patients with liver injury. Methods: We conducted this multicenter, retrospective study in five designated hospitals for COVID-19 management. Laboratory-confirmed COVID-19 patients were enrolled and classified into the normal live function group and liver dysfunction group according to liver enzymes, bilirubin, and albumin on admission, respectively. Data of baseline, clinical manifestations, and outcomes were collected and compared in the paired groups. Results: Of the 649 included COVID-19 patients, 200 (30.8%), 69 (10.6%), and 267 (41.1%) patients had elevated liver enzymes, increased bilirubin, and low-level albumin, respectively. Fever, cough, and dyspnea were the most common symptoms and showed an increased proportion in the liver dysfunction group. Compared with patients in the normal liver function group, patients with liver dysfunction manifested decreased lymphocytes, higher level of leukocytes, neutrophils, inflammatory indicators, and cytokines, as well as more severe impairment in kidney function and myocardium. They were more likely to show bilateral involvement and more pulmonary lobes involved according to chest images. With increased proportion of patients who developed severe/critical conditions and needed mechanical ventilation and systemic glucocorticoid therapy, patients with liver dysfunction on admission showed significantly higher in-hospital mortality. Moreover, cardiac troponin I ≥1.5 ng/mL was identified as an independent mortality predictor in the elevated liver enzymes group. Conclusion: Patients with liver dysfunction on admission had worse clinical manifestation, and resulted in higher rate of severe/critical type, receiving mechanical ventilation and in-hospital mortality.
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Background: The management of prolonged air leakage (PAL) is a significant clinical challenge, particularly for patients who are unfit for surgical treatment. The use of endoscopic interventions with occlusive devices has been reported previously; however, local availability and cost may represent potential hurdles, especially in developing countries. In this study, we presented a conical endobronchial plug of our design and evaluated the efficacy of making use of that in the treatment of PAL as a novel method. Methods: This retrospective study included a total of 23 patients with PAL who were not suitable for surgery and underwent bronchial occlusion using customized plugs. The responsible bronchi were identified by the balloon occlusion test or by end-tidal carbon dioxide detection. In each case, the plug was grasped at the knot of the tip with forceps and then inserted into the target bronchus with a flexible bronchoscope. Results: Of the 23 patients with intractable pneumothorax, 1 to 3 plugs (median =1) were successfully inserted into the affected bronchi of each patient for bronchial occlusion. Air leakage showed complete cessation in 13 patients (56.5%) and reduction in seven patients (30.4%). A total of 20 patients (87.0%) experienced successful removal of the drainage tube following plug occlusion or presented with additional pleurodesis. Complications included expectoration of the plug (n=1) and fever (n=1); no other severe complications were observed. Conclusions: Bronchial occlusion using customized endobronchial plugs appears to be an effective and simple option for the management of PAL in patients who are not suitable for surgery, especially in developing countries, as the customized plug is a cost-effective alternative.
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Previous studies have highlighted CRISPR-based nucleic acid detection as rapid and sensitive diagnostic methods for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we reported an optimized CRISPR-Cas12a diagnostic platform for the safe and rapid detection of SARS-CoV-2 variants of concern (VOCs). This platform, which was referred to as CALIBURN-v2, could complete the diagnosis on extracted RNA samples within 25 min in a closed-lid reaction mode and had 100-fold increase in detection sensitivity in comparison with previous platforms. Most importantly, by integrating a portable device and smartphone user interface, CALIBURN-v2 allowed for cloud server-based data collection and management, thus transforming the point-of-care testing (POCT) platform to internet of medical things (IoMT) applications. It was found that IoMT-enabled CALIBURN-v2 could achieve 95.56% (172 out of 180) sensitivity for SARS-CoV-2 wild type and 94.38% (84 out of 89) overall sensitivity for SARS-CoV-2 variants including Delta and Omicron strains. Therefore, our study provides a feasible approach for IoMT-enabled CRISPR diagnostics for the detection of SARS-CoV-2 VOCs.
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Purpose: Surgical bullectomy is the standard treatment of giant emphysematous bulla (GEB). However, bronchoscopic treatment should be considered as an alternative approach for patients who are unfit for surgical treatment. The study aimed to evaluate the clinical efficacy of endobronchial occlusion for the treatment of GEB using silicone plugs. Methods: This retrospective study recruited four patients with GEB who were unsuitable for surgery. Preoperative planning was performed using high-resolution computed tomography and a virtual bronchoscopic navigation system. Customized silicone plugs were then placed in the target airway via bronchoscopy to cause GEB regression and atelectasis. Results: All procedures were completed successfully in four patients. Three months after the procedures, compared with baseline, increases in the mean forced expiratory volume in 1 s (from 1.20 L/s to 1.33 L/s), forced vital capacity (from 2.63 L to 2.90 L), diffusion lung capacity for carbon monoxide (from 29% to 41% of the predicted value) and 6-minute walking test (from 412 m to 474 m) were observed. Additionally, the mean total lung capacity (from 6.80 L to 6.35 L), residual volume (from 3.97 L to 3.52 L), and St. George's Respiratory Questionnaire scores (from 67 to 45) were all lower than baseline data. Conclusion: Our preliminary results demonstrated that the endobronchial placement of silicone plugs could be a low-cost, safe, and effective choice for the treatment of GEB in surgically unfit patients.
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Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Vesícula/diagnóstico por imagem , Vesícula/cirurgia , Broncoscopia/métodos , Volume Expiratório Forçado , Humanos , Pneumonectomia/métodos , Doença Pulmonar Obstrutiva Crônica/cirurgia , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/cirurgia , Estudos Retrospectivos , Silicones , Resultado do TratamentoRESUMO
BACKGROUND: To determine whether rat offspring born under conditions of chronic intermittent hypoxia (CIH) would develop systemic inflammation and be susceptible to CIH-mediated injury on artery. METHODS: CIH rat model was established. The expression levels of p38MAPK, NF-κB p65, CRP, TNFα, and IL-8 were measured. The arterial pathology of offspring whose mothers were exposed to CIH during pregnancy was evaluated. RESULTS: The levels of p-P38MAPK and NF-κB p65 were significantly up-regulated following induction of intra-uterine CIH Induction of intra- and extra-uterine CIH had an interaction regarding the expression profiles of these markers (P < 0.01, P < 0.01, P < 0.01, P < 0.01, P = 0.020, respectively). Pathologic analysis of the arteries confirmed that intra-uterine CIH increased the tunica intima thickness (P < 0.01), but had no effect on the tunica media (P = 0.974). Furthermore, induction of intra- and extra-uterine CIH had a synergistic interaction on tunica intima thickness (P = 0.004). CONCLUSIONS: Intra-uterine CIH caused tunica intima thickening and development of pre-atherosclerotic lesions in offspring via NF-κB p65 and p-p38 MAPK. Furthermore, the expression of NF-κB p65 and p-p38 MAPK and the extent of pre-atherosclerotic lesions were either exacerbated or alleviated in offspring when re-exposed to CIH later.
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Aterosclerose , Hipóxia , Efeitos Tardios da Exposição Pré-Natal , Animais , Aterosclerose/etiologia , Feminino , Hipóxia/complicações , Inflamação , Gravidez , Ratos , Fator de Transcrição RelA , Túnica Íntima , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
The outbreak of novel coronavirus SARS-CoV-2 has caused a worldwide threat to public health. COVID-19 patients with SARS-CoV-2 infection can develop clinical symptoms that are often confused with the infections of other respiratory pathogens. Sensitive and specific detection of SARS-CoV-2 with the ability to discriminate from other viruses is urgently needed for COVID-19 diagnosis. Herein, we streamlined a highly efficient CRISPR-Cas12a-based nucleic acid detection platform, termed Cas12a-linked beam unlocking reaction (CALIBURN). We show that CALIBURN could detect SARS-CoV-2 and other coronaviruses and influenza viruses with little cross-reactivity. Importantly, CALIBURN allowed accurate diagnosis of clinical samples with extremely low viral loads, which is a major obstacle for the clinical applications of existing CRISPR diagnostic platforms. When tested on the specimens from SARS-CoV-2-positive and negative donors, CALIBURN exhibited 73.0% positive and 19.0% presumptive positive rates and 100% specificity. Moreover, unlike existing CRISPR detection methods that were mainly restricted to respiratory specimens, CALIBURN displayed consistent performance across both respiratory and nonrespiratory specimens, suggesting its broad specimen compatibility. Finally, using a mouse model of SARS-CoV-2 infection, we demonstrated that CALIBURN allowed detection of coexisting pathogens without cross-reactivity from a single tissue specimen. Our results suggest that CALIBURN can serve as a versatile platform for the diagnosis of COVID-19 and other respiratory infectious diseases.
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Proteínas de Bactérias/genética , Teste de Ácido Nucleico para COVID-19/métodos , COVID-19/diagnóstico , Proteínas Associadas a CRISPR/genética , Sistemas CRISPR-Cas , Endodesoxirribonucleases/genética , RNA Viral/análise , SARS-CoV-2/química , Adenoviridae/química , Animais , COVID-19/genética , Corantes Fluorescentes/química , Humanos , Limite de Detecção , Camundongos Endogâmicos BALB C , Técnicas de Amplificação de Ácido Nucleico , Sondas RNA/genética , RNA Viral/genética , Manejo de Espécimes , Espectrometria de FluorescênciaRESUMO
Tracheobronchial fistula (TBF) is a challenging management condition. Several bronchoscopic procedures have been tried for fistula closure. However, none has been found to be superior to the others. We herein describe a novel technique involving the submucosal injection of autologous platelet-rich plasma (auto-PRP) around the fistula to close the TBF. After auto-PRP treatment, all 3 TBF patients have successfully healed. No treatment-related complications and fistula-related symptoms were detected. Thus, this application of auto-PRP for fistula closure is a feasible and cost-effective strategy and could be recommended as a valuable therapeutic alternative for repairing postoperative TBF.
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Fístula Brônquica/terapia , Broncoscopia/métodos , Plasma Rico em Plaquetas , Doenças da Traqueia/terapia , Idoso , Fístula Brônquica/diagnóstico , Fístula/diagnóstico , Fístula/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Doenças da Traqueia/diagnósticoRESUMO
PURPOSE: To predict the risk of developing severe pneumonia among mild novel coronavirus pneumonia (mNCP) patients on admission. METHODS: A retrospective cohort study was conducted at three hospitals in Shanghai and Wuhan from January 2020 to February 2020. Real-time polymerasechain-reaction assays were used to detect COVID-19. A total of 529 patients diagnosed with NCP were recruited from three hospitals and classified by four severity types during hospitalization following the standards of the Chinese Diagnosis and Treatment of Pneumonia Caused by New Coronavirus Infection (eighth version). Patients were excluded if admitted by ICU on admission (n=92, on a general ward while meeting the condition of severe or critical type on admission (n=25), or there was insufficient clinical information (n=64). In sum, 348 patients with mNCP were finally included, and 68 developed severe pneumonia. RESULTS: mNCP severity prognostic index values were calculated based on multivariate logistic regression: history of diabetes (OR 2.064, 95% CI 1.010-4.683; p=0.043), time from symptom onset to admission ≥7 days (OR 1.945, 95% CI 1.054-3.587; p=0.033), lymphocyte count ≤0.8 (OR 1.816, 95% CI 1.008-3.274; p=0.047), myoglobin ≥90 mg/L (OR 2.496, 95% CI 1.235-5.047; p=0.011), and D-dimer ≥0.5 mg/L (OR 2.740, 95% CI 1.395-5.380; p=0.003). This model showed a c-statistics of 0.747, with sensitivity and specificity 0.764 and 0.644, respectively, under cutoff of 165. CONCLUSION: We designed a clinical predictive tool for risk of severe pneumonia among mNCP patients to provided guidance for medicines. Further studies are required for external validation.
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BACKGROUND: In December 2019, a novel communicable disease, novel coronavirus infected pneumonia (NCIP) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) broke out. We aimed to analyze the characteristics and severity of patients with myocardial damage in NCIP. METHODS: We enrolled 215 adult patients with NCIP from January 2020 to February 2020. Outcomes were followed up until March 1st, 2020. RESULTS: 28.37% of the total patients showed increased level of TnI (> 0.040â¯ng/ml). Patients were older and had more cardiovascular complications in increased TnI group. Higher CRP, NT-proBNP, lower immune CD3, CD4 and CD8 cell account and more involved lobes detected by CT scan in the lung were observed in increased TnI group. Patients with elevated TnI had higher CURB-65 scores and were more likely given glucocorticoid therapy and mechanical ventilation than patients in normal TnI group. CONCLUSIONS: Markers of cardiomyocyte injury were elevated not least in elderly males with pre-existing cardiovascular disease. Patients with elevated TnI presented more severe situation, leading to multiple organ dysfunctions, which appeared as a pivotal feature of patients with NCIP that requires attention by clinicians in order to provide necessary treatment as soon as possible and improve patients' outcomes.
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Rationale: The coronavirus disease (COVID-19) pandemic is now a global health concern.Objectives: We compared the clinical characteristics, laboratory examinations, computed tomography images, and treatments of patients with COVID-19 from three different cities in China.Methods: A total of 476 patients were recruited from January 1, 2020, to February 15, 2020, at three hospitals in Wuhan, Shanghai, and Anhui. The patients were divided into four groups according to age and into three groups (moderate, severe, and critical) according to the fifth edition of the Guidelines on the Diagnosis and Treatment of COVID-19 issued by the National Health Commission of China.Measurements and Main Results: The incidence of comorbidities was higher in the severe (46.3%) and critical (67.1%) groups than in the moderate group (37.8%). More patients were taking angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers in the moderate group than in the severe and critical groups. More patients had multiple lung lobe involvement and pleural effusion in the critical group than in the moderate group. More patients received antiviral agents within the first 4 days in the moderate group than in the severe group, and more patients received antibiotics and corticosteroids in the critical and severe groups. Patients >75 years old had a significantly lower survival rate than younger patients.Conclusions: Multiple organ dysfunction and impaired immune function were the typical characteristics of patients with severe or critical illness. There was a significant difference in the use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers among patients with different severities of disease. Involvement of multiple lung lobes and pleural effusion were associated with the severity of COVID-19. Advanced age (≥75 yr) was a risk factor for mortality.
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Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/fisiopatologia , Adulto , Fatores Etários , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Betacoronavirus , COVID-19 , China/epidemiologia , Comorbidade , Infecções por Coronavirus/mortalidade , Estado Terminal , Feminino , Mortalidade Hospitalar , Humanos , Incidência , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/virologia , Pandemias , Derrame Pleural/virologia , Pneumonia Viral/mortalidade , SARS-CoV-2 , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: The objective of our research was to explore the effects of maternal and postpartum chronic intermittent hypoxia (CIH) exposure on atherosclerosis in adulthood offspring of rats, and the role of Caveolin-1 in the course. METHODS: Sixteen rats were assigned to two groups (n = 8), maternal normoxia and CIH group. After delivery, two male pups per litter were selected and breastfed for 1 month, which then randomly received postpartum normoxia or CIH. Thus, 4 groups were created as follows (n = 8): (1) maternal normoxia and postpartum normoxia group, (2) maternal CIH and postpartum normoxia group, (3) maternal CIH and postpartum CIH group, and (4) maternal normoxia and postpartum CIH group. The offspring were weighed at birth and weaning. After the duration of 12-week experiment, morphological changes, the expression of Caveolin-1 and NF-κB p65 in the aorta were detected. RESULTS: Maternal CIH resulted in significantly lower body weight and thicker intima (P < 0.001). CIH upregulated the expression of Caveolin-1 and NF-κB p65 significantly (P < 0.01). There was a synergistic effect of maternal and postpartum CIH on the thickening of intima (P < 0.05), also on the expression of Caveolin-1 and NF-κB p65 (P < 0.01). CONCLUSIONS: The results demonstrate that maternal CIH exposure causes a postpartum catch-up growth and early atherosclerotic changes followed by upregulating Caveolin-1 expression. Besides, maternal CIH enhances the atherosclerotic changes caused by postpartum CIH. Oxidative stress probably implicates in above effects.
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Aterosclerose/genética , Caveolina 1/genética , Hipóxia Fetal/complicações , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal , Animais , Animais Recém-Nascidos , Aorta/metabolismo , Aterosclerose/sangue , Caveolina 1/sangue , Doença Crônica , Feminino , Hipóxia Fetal/patologia , Expressão Gênica/genética , Masculino , Oxigênio/sangue , Período Pós-Parto , Gravidez , Ratos , Fator de Transcrição RelA/genética , Túnica Íntima/metabolismo , Regulação para Cima/genéticaRESUMO
Closure of bronchopleural fistula remains a difficult challenge for clinicians. Although several therapeutic approaches have been proposed, the clinical results are commonly unsatisfactory. Previous reports have indicated that autologous mesenchymal stem cells (MSCs) are useful for aiding treatment of bronchopleural fistula. We report here the use of umbilical cord MSCs to effect the successful closure of a bronchopleural fistula (5 mm) in a 33-year-old woman 6 months after a lobectomy. A review of the relevant literature is included. The use of MSCs may be a promising therapeutic method for the closure of bronchopleural fistula. Randomized controlled trials with larger samples are required.
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Fístula Brônquica/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Doenças Pleurais/terapia , Pneumonectomia/efeitos adversos , Adulto , Fístula Brônquica/diagnóstico , Broncoscopia , Feminino , Fístula/diagnóstico , Fístula/terapia , Humanos , Injeções , Doenças Pleurais/diagnóstico , Complicações Pós-Operatórias/terapia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Location of the affected bronchus of pleural air leaks is the most important step of trans-bronchoscopic bronchial occlusion for the treatment of intractable pneumothorax. The balloon occlusion test is the most commonly used technique, but has failed in some cases. The aim of the present study was: (1) to determine if endo-bronchial end-tidal CO2 (EtCO2) measurement can identify the affected bronchus that is the source of a persistent pleural air leak; and (2) to establish a methodology for endo-bronchial EtCO2 testing in locating affected bronchus in intractable pneumothorax. METHODS: A total of 28 patients with intractable pneumothorax underwent bronchoscopy with (1) the balloon occlusion test for the identification of the affected bronchus; and (2) endo-bronchial EtCO2 measurement (EtCO2 test) at the orifices of the bronchus of the affected lung. The effectiveness of these two methods of affected bronchus identification were compared. The threshold EtCO2 (T-EtCO2) was determined. RESULTS: The positive rates of locating the affected bronchus by the endo-bronchial EtCO2 test, balloon occlusion test, and combination of the two techniques were 60.7% (17/28), 64.3% (18/28) and 96.4% (27/28), respectively. The average differences in EtCO2 between the affected bronchus and the main carina, main bronchus, and non-affected bronchus were (in mmHg) 4.41 ± 1.99 (95% confidence interval: 3.5, 5.3), 4.73 ± 2.10 (3.80, 5.66 ) and 5.57 ± 2.53 (4.45, 6.69), respectively. CONCLUSIONS: (1) The endo-bronchial EtCO2 test is complementary to the balloon occlusion test of the leading bronchus. (2) A threshold (T-EtCO2) value of >5 mmHg is optimal for this technique.
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Testes Respiratórios/métodos , Brônquios/metabolismo , Broncoscopia/métodos , Dióxido de Carbono/metabolismo , Pneumotórax/diagnóstico , Idoso , Biomarcadores/metabolismo , Testes Respiratórios/instrumentação , Brônquios/fisiopatologia , Broncoscópios , Broncoscopia/instrumentação , Catéteres , Humanos , Masculino , Pessoa de Meia-Idade , Pneumotórax/metabolismo , Pneumotórax/fisiopatologia , Pneumotórax/terapia , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
Lung cancer is reported to be a major public health issue worldwide and the overall prognosis of patients remains poor. The expression levels of Livin and Survivin, of the inhibitors of apoptosis (IAP) family, are associated with prognostic significance in the majority of solid tumors. Therefore, in the presents study, short hairpin (sh)RNA expression vectors inhibiting the Livin and Survivin genes were constructed to examine the effects of the transfection of Livin shRNA and/or Survivin shRNA on the biological functions of tumor cells. The transfection efficiency was measured using fluorescence reverse transcriptionquantitative polymerase chain reaction and western blot analyses. The cell growth inhibition ratio was measured using a CCK assay. Cell apoptosis following transfection and in tumor tissues were measured using a TUNEL assay, and a cancer xenograft model was used to investigate the effect of Livin shRNA and/or Survivin shRNA on tumor growth. The results indicated that the mRNA and protein expression levels were suppressed following the transfection of Livin and Survivin shRNA into tumor cells (P<0.05, compared with control group). The growth of tumor cells in vivo and in vitro was significantly inhibited following transfection with Livin and Survivin shRNA, compared with that in the other groups (P<0.05). Taken together, the transfection of cells with Livin and Survivin inhibited tumor growth in vivo and in vitro, with the cotransfection of Livin and Survivin shRNA showing increased efficiency, compared with transfection of either the Livin vector or Survivin vector alone. The combined inhibition of Livin and Survivin may be a promising multitargeted gene therapeutic strategy in cancer treatment.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , Proteínas de Neoplasias/metabolismo , RNA Interferente Pequeno/metabolismo , Células A549 , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Apoptose , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células , Humanos , Proteínas Inibidoras de Apoptose/antagonistas & inibidores , Proteínas Inibidoras de Apoptose/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Interferência de RNA , RNA Mensageiro/metabolismo , Survivina , Transfecção , Transplante HeterólogoAssuntos
Fístula Brônquica/cirurgia , Fístula/cirurgia , Doenças Pleurais/cirurgia , Complicações Pós-Operatórias/cirurgia , Próteses e Implantes , Adenocarcinoma/cirurgia , Fístula Brônquica/diagnóstico por imagem , Broncoscopia , Empiema/diagnóstico por imagem , Empiema/cirurgia , Fístula/diagnóstico por imagem , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Doenças Pleurais/diagnóstico por imagem , Pneumonectomia , Complicações Pós-Operatórias/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
The aim of the present study was to explore the expression of POLD4 in human lung adenocarcinoma A549 cells under 4-nitroquinoline-1-oxide (4NQO) stimulation to investigate the role of POLD4 in smoking-induced lung cancer. The lung cancer A549 cell line was treated with 4NQO, with or without MG132 (an inhibitor of proteasome activity), and subsequently the POLD4 level was determined by western blot analysis. Secondly, the cell sensitivity to 4NQO and Taxol was determined when the POLD4 expression level was downregulated by siRNA. The POLD4 protein levels in the A549 cells decreased following treatment with 4NQO; however, MG132 could reverse this phenotype. Downregulation of the POLD4 expression by siRNA enhanced A549 cell sensitivity to 4NQO, but not to Taxol. In conclusion, 4NQO affects human lung adenocarcinoma A549 cells by regulating the expression of POLD4.
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OBJECTIVE: To evaluate the effect of end-tidal carbon dioxide (EtCO2) detection for location of the leading bronchus in patients with pneumothorax. METHODS: Transbronchoscopic EtCO2 detection was performed in 4 patients with intractable pneumothorax in whom transbronchoscopic balloon detection failed to localize the leading bronchus. A specific bronchus was suspected to be the leading bronchus when its EtCO2 value was significantly lower than that of the main bronchus of the affected lung. After the pleural air leakage was successfully sealed by bronchial occlusion of the suspected bronchus, the EtCO2 was confirmed to indicate the leading bronchus. RESULTS: Transbronchoscopic EtCO2 detection successfully located the leading bronchus in all 4 patients. CONCLUSIONS: Transbronchoscopic EtCO2 detection is a new method of locating the leading bronchus in patients with intractable pneumothorax.
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Broncopatias , Pneumotórax , Brônquios , Dióxido de Carbono , Humanos , Pulmão , PleuraRESUMO
Previously, we have shown that downregulation of POLD4 in lung cancer cells delays progression through the G1-S cell cycle transition and leads to increased genomic instability. To date however, detailed molecular mechanisms have not been elucidated to explain how this occurs. In the present study, we found that reduction in POLD4 by siRNA knockdown promoted downregulation of both p-Akt Ser473 and Skp2 as well as upregulation of p27. Furthermore, these protein expression levels were rescued when siRNA-resistant POLD4 was ectopically expressed in the knockdown cells. These data suggest that the POLD4 downregulation is associated with impaired Akt-Skp2-p27 pathway in lung cancer.