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1.
J Thorac Oncol ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32007598

RESUMO

INTRODUCTION: Alflutinib (AST2818) is a newly developed third-generation EGFR tyrosine kinase inhibitor (TKI) selective for EGFR sensitizing and T790M resistant mutations. We assessed the safety, efficacy and pharmacokinetics (PK) of alflutinib in advanced NSCLC patients with confirmed T790M mutation, who progressed after the first- or second-generation EGFR-TKI therapy. METHODS: In the dose-escalation (NCT02973763) and dose-expansion (NCT03127449) studies, patients received alflutinib orally until disease progression, unacceptable toxicity, or subject withdrawal. Primary endpoints were the safety, tolerability, and PK for the dose-escalation study, and the objective response rate (ORR, assessed by an independent radiological review committee) for the dose-expansion study. RESULTS: Between Nov 30, 2016, and Jul 24, 2018, 130 patients (14 in dose-escalation, 116 in dose-expansion) received alflutinib treatment (20, 40, 80, 160, or 240 mg once daily). By Oct 30, 2018, 79 (61%) patients remained on treatment. No dose limiting toxicities were observed in the dose-escalation study. In the dose-expansion study (40 - 240 mg), the overall ORR was 76.7% (89/116), and it was 70.6% (12/17) in patients with CNS metastases. 79% (103/130) of all patients had possibly treatment-related adverse events (AEs); 8% (11/130) had treatment-related grade ≥3 AEs. Serious adverse events (SAEs) were reported in 15% (20/130) of patients, and two SAEs were treatment related. No clear dose-response (antitumor activity and AEs) relationships were observed. Exposures to alflutinib and its active metabolite (AST5902) were comparable at steady state. CONCLUSIONS: Alflutinib was clinically effective with an acceptable toxicity profile in advanced NSCLC patients (including those with CNS metastases) with EGFR T790M mutation. Further investigation is ongoing.

2.
BMC Genomics ; 21(1): 39, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931709

RESUMO

BACKGROUND: Hypoxia mediated pulmonary hypertension (HPH) is a lethal disease and lacks effective therapy. CircRNAs play significant roles in physiological process. Recently, circRNAs are found to be m6A-modified. The abundance of circRNAs was influenced by m6A. Furthermore, the significance of m6A circRNAs has not been elucidated in HPH yet. Here we aim to investigate the transcriptome-wide map of m6A circRNAs in HPH. RESULTS: Differentially expressed m6A abundance was detected in lungs of HPH rats. M6A abundance in circRNAs was significantly reduced in hypoxia in vitro. M6A circRNAs were mainly from protein-coding genes spanned single exons in control and HPH groups. Moreover, m6A influenced the circRNA-miRNA-mRNA co-expression network in hypoxia. M6A circXpo6 and m6A circTmtc3 were firstly identified to be downregulated in HPH. CONCLUSION: Our study firstly identified the transcriptome-wide map of m6A circRNAs in HPH. M6A can influence circRNA-miRNA-mRNA network. Furthermore, we firstly identified two HPH-associated m6A circRNAs: circXpo6 and circTmtc3. However, the clinical significance of m6A circRNAs for HPH should be further validated.

3.
Oncol Lett ; 18(6): 5859-5870, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31788059

RESUMO

Lung cancer is the leading cause of cancer-related mortality worldwide. Despite progress in the treatment of non-small-cell lung cancer, there are limited treatment options for lung squamous cell carcinoma (LUSC), compared with lung adenocarcinoma. The present study investigated the disease mechanism of LUSC in order to identify key candidate genes for diagnosis and therapy. A total of three gene expression profiles (GSE19188, GSE21933 and GSE74706) were analyzed using GEO2R to identify common differentially expressed genes (DEGs). The DEGs were then investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. A protein-protein interaction (PPI) network was constructed via the Search Tool for the Retrieval of Interacting Genes/Proteins, and visualized using Cytoscape software. The expression levels of the hub genes identified using CytoHubba were validated using the University of California, Santa Cruz (UCSC) database and the Human Protein Atlas. A Kaplan-Meier curve and Gene Expression Profiling Interactive Analysis were then employed to evaluate the associated prognosis and clinical pathological stage of the hub genes. Furthermore, non-coding RNA regulatory networks were constructed using the Gene-Cloud Biotechnology information website. A total of 359 common DEGs (155 upregulated and 204 downregulated) were identified, which were predominantly enriched in 'mitotic nuclear division', 'cell division', 'cell cycle' and 'p53 signaling pathway'. The PPI network consisted of 257 nodes and 2,772 edges, and the most significant module consisted of 66 upregulated genes. A total of 19 hub genes exhibited elevated RNA levels, and 10 hub genes had elevated protein levels compared with normal lung tissues. The upregulation of five hub genes (CCNB1, CEP55, FOXM1, MKI67 and TYMS; defined in Table I) were significantly associated with poor overall survival and unfavorable clinical pathological stages. Various ncRNAs, such as C1orf220, LINC01561 and MGC39584, may also play important roles in hub-gene regulation. In conclusion, the present study provides further understanding of the pathogenesis of LUSC, and reveals CCNB1, CEP55, FOXM1, MKI67 and TYMS as potential biomarkers or therapeutic targets.

4.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 36(6): 893-901, 2019 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-31875361

RESUMO

Alzheimer's disease (AD) is a chronic central neurodegenerative disease. The pathological features of AD are the extracellular deposition of senile plaques formed by amyloid-ß oligomers (AßOs) and the intracellular accumulation of neurofibrillary tangles formed by hyperphosphorylated tau protein. In this paper, an in vitro pathological model of AD based on neuronal network chip and its real-time dynamic analysis were presented. The hippocampal neuronal network was cultured on the microelectrode array (MEA) chip and induced by AßOs as an AD model in vitro to simultaneously record two firing patterns from the interneurons and pyramidal neurons. The spatial firing patterns mapping and cross-correlation between channels were performed to validate the degeneration of neuronal network connectivity. This biosensor enabled the detection of the AßOs toxicity responses, and the identification of connectivity and interactions between neuronal networks, which can be a novel technique in the research of AD pathological model in vitro.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Humanos , Emaranhados Neurofibrilares , Proteínas tau
5.
Medicine (Baltimore) ; 98(51): e18386, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31861001

RESUMO

RATIONALE: Pulmonary embolisms (PEs) are caused by emboli, which mostly originate from deep venous thrombi that travel to and suddenly block the pulmonary arteries. The emboli are usually thrombi, and right atrial myxoma emboli are rare. PATIENT CONCERNS: A 55-year-old man presented with shortness of breath and syncope. We proceeded with computed tomography pulmonary angiography (CTPA) and transthoracic echocardiogram (TTE), the results of which suggested that the diagnosis was a right atrial mass. DIAGNOSIS: A definitive diagnosis compatible with a right atrial myxoma (RAM) with tumoral pulmonary emboli after surgical excision was made. INTERVENTION: Right atrial and pulmonary artery embolectomy. OUTCOMES: The patient followed an uneventful course during the 6 years of follow-up after surgery. According to a review of the literature, RAMs are often not diagnosed in a timely manner or even go completely undiagnosed. TTE, transesophageal echocardiography (TEE), CT, magnetic resonance imaging (MRI), and positron emission tomography/computed tomography may be helpful in the preoperative diagnosis. Surgical removal of the masses from the atrium and pulmonary arteries was relatively uneventful. LESSONS: RAMs should be considered unlikely reasons for fatal pulmonary embolisms.


Assuntos
Átrios do Coração/diagnóstico por imagem , Neoplasias Cardíacas/diagnóstico por imagem , Mixoma/diagnóstico por imagem , Embolia Pulmonar/etiologia , Angiografia por Tomografia Computadorizada , Ecocardiografia , Átrios do Coração/cirurgia , Neoplasias Cardíacas/patologia , Neoplasias Cardíacas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Mixoma/patologia , Mixoma/cirurgia , Embolia Pulmonar/cirurgia
6.
Curr Med Chem ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31724496

RESUMO

At least a proportion of patients suffering from chronic inflammatory airway diseases respond poorly to the bronchodilator and corticosteroid therapies. There is a need for the development of improved anti-inflammatory treatment. Insulin growth factor 1 (IGF1) and insulin participates in not only metabolism and glucose homeostasis, but also many other physiological and pathophysiological processes, including growth and inflammation. Recently, it has been shown that not only the classical IGF1 and IGF1 receptor (IGF1R), but also the other molecules in the IGF1/insulin network, including insulin, insulin-like growth factor-binding protein(IGFBP) and IGFBP protease, have roles in chronic inflammatory airway diseases. This review aims to provide a comprehensive insight into recent endeavors devoted to the role of the IGF1/insulin network in chronic inflammatory airway diseases. Its participation in airway inflammation, remodeling and hyper-responsiveness (AHR), as well as acute exacerbation has been conclusively demonstrated. Its possible relations to glucocorticoid insensitivity has also been indicated. A better understanding of the IGF1/insulin network by further bench-to-bedside research may provide us with rational clinical therapeutic approaches against chronic inflammatory airway diseases.

7.
Int J Chron Obstruct Pulmon Dis ; 14: 1559-1566, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409982

RESUMO

Objective: The purpose of this study was to explore the insulin level in the serum of chronic obstructive pulmonary disease (COPD) patients during acute exacerbation (AE). Methods: The study population consisted of 22 acute exacerbation chronic obstructive pulmonary disease (AECOPD) patients, 20 COPD patients and 20 healthy controls. Fasting blood glucose, insulin and serum lipid levels were measured. After the patients recovered from AE, the insulin and glucose levels were also analyzed. Results: Insulin level, glucose level and homeostasis model assessment of insulin resistance (HOMA-IR) of AECOPD patients were higher than healthy controls (7.19±6.02 vs 3.28±1.09 µIU/mL, P<0.05, 126.61±50.92 vs 96.21±12.66 mg/dL, P<0.05, 2.66±2.72 vs 0.78±0.26, P<0.05). For stable COPD patients, the insulin level, glucose level and HOMA-IR were 6.52±2.56 µIU/mL, 95.58±11.44 mg/dL, and 1.52±0.53, respectively. The triglyceride (TG) level, total cholesterol (CHOL) level and low-density lipoprotein cholesterol (LDL-CHOL) level were decreased in AECOPD patients (0.78±0.33 vs 1.05±0.35 mmol/L, P<0.05, 3.88±0.72 vs 4.49±0.7 mmol/L, P<0.05, 2.01±0.59 vs 2.59±0.58 mmol/L, P<0.05). When the patients had recovered from AE, the insulin levels increased (10.67±6.22 vs 7.12±6.19 µIU/mL, P<0.05) and the glucose levels decreased (122.69±41.41 vs 134.08±53.19 mg/dL, P>0.05). Conclusion: A high insulin level and a high HOMA-IR status in COPD patients were demonstrated. Downregulated levels of insulin during AE compared with the convalescent state were detected, while the variation in the glucose level was not as great as expected, indicating a potentially important role for insulin in AECOPD.

8.
Medicine (Baltimore) ; 98(6): e14437, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30732204

RESUMO

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized, immune-mediated chronic fibrotic inflammation that can involve almost all organs, causing tumefaction and dysfunction. Its presence in pulmonary circulation is underestimated and has not yet been investigated. OBJECTIVES: We describe a representative IgG4-RD patient with pulmonary artery stenosis and pulmonary embolism, leading to reversible pulmonary hypertension. Literature review of IgG4-RD with pulmonary circulation involvement was conducted. DATA SOURCES: References for this review were identified through searches via PubMed, EBSCO, and Web of Science for published articles before November 2016. RESULTS: There were 15 published cases of IgG4-RD with pulmonary vascular involvement, 3 with pulmonary arteritis, 2 with pulmonary artery aneurysm, 3 with pulmonary artery stenosis, 1 with obliterative phlebitis, and 1 with pulmonary embolism. Possible immunity and inflammation mechanisms were summarized. CONCLUSIONS: IgG4-RD with pulmonary vascular involvement is rare. Echocardiogram and contrast-enhanced chest CT are helpful to screen the disease. Clinical manifestations were found from asymptomatic to dyspnea or even syncope. And nearly all cases had more than 1 organ affected, with significantly increased serum IgG4 levels. PET/CT aided in identifying affected organs and determining candidate biopsy sites. More awareness is urged to evaluate the pulmonary vascular manifestations of this disease.


Assuntos
Hipertensão Pulmonar/complicações , Doença Relacionada a Imunoglobulina G4/complicações , Doença Relacionada a Imunoglobulina G4/patologia , Embolia Pulmonar/complicações , Estenose de Artéria Pulmonar/complicações , Ecocardiografia , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia Torácica
9.
Thromb Res ; 176: 85-94, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30784777

RESUMO

INTRODUCTION: Acute pulmonary embolism (APE) is a cardiovascular disease with high morbidity and mortality. Although the anatomical obstruction of the pulmonary vascular bed initiates APE, recent studies have suggested that vasoconstrictors in the renin-angiotensin system (RAS) play a role in the severity of APE. MATERIALS AND METHODS: We performed a 5-year retrospective clinical study to analyze the key RAS components in APE patients, including angiotensin converting enzyme (ACE), ACE2, angiotensin II (Ang II) and angiotensin 1-7(Ang(1-7)). The role of RhoA-Rho associated kinase (ROCK) signaling in regulating RAS vasoconstrictors was detected in rat pulmonary artery endothelial cells and in an APE rat model. RESULTS: In clinical study, we found that the levels of RAS vasoconstrictors were correlated with the clinical classification of APE patients, ACE and Ang II were unregulated, whereas ACE2 and Ang(1-7) were downregulated in the high-risk group compared to the healthy volunteers. In animal study, we found that activated RhoA-ROCK signaling was responsible for the imbalance in RAS vasoconstrictors both in vitro and in vivo, and further evidence indicated that ROCK inhibitors (Y27632 or HA1077) and an ACE2 activator (Resorcinol naphthalein) restored the dysregulated RAS vasoconstrictors significantly and had a protective role in an APE rat model. CONCLUSIONS: Our study revealed that RhoA-ROCK signaling leads to RAS imbalance in APE patients, and ACE2 activation might be a novel therapeutic target in APE treatment.


Assuntos
Peptidil Dipeptidase A/metabolismo , Embolia Pulmonar/metabolismo , Transdução de Sinais , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , Doença Aguda , Animais , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ratos Sprague-Dawley , Sistema Renina-Angiotensina
10.
J Aerosol Med Pulm Drug Deliv ; 32(1): 34-39, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30199313

RESUMO

BACKGROUND: Airway pressure release ventilation (APRV) maintains a sustained airway pressure over a large proportion of the respiratory cycle, and has a long inspiratory time at high pressure. The purpose of this study was to determine the influence of the APRV with and without spontaneous breathing on albuterol aerosol delivery with a continuous vibrating-mesh nebulizer (VMN) placed at different positions on an adult lung model of invasive mechanical ventilation. METHODS: An adult lung model was assembled by connecting a ventilator with a dual-limb circuit to an 8-mm inner diameter endotracheal tube (ETT) and collecting filter attached to a test lung with set compliance of 0.1 L/cmH2O and resistance of 0.5 cmH2O/(L·s). Four ventilator modes were compared: pressure control ventilation (PCV) with no bias flow, PCV with bias flow of 6 L/min (PCVBF6), APRV with no spontaneous breaths (APRV), and APRV with spontaneous breath trigger (APRVs). Peak inspiratory pressure, peak end-expiratory pressure, aerosol dose, and nebulization time were similar for all modes. The VMN was placed (1) between Y-piece and inspiratory limb, (2) at the gas outlet of a heated humidifier, and (3) at the gas inlet of a heated humidifier. Albuterol sulfate (5 mg/2.5 mL) was administered with each run and collected on a filter distal to the ETT. Deposited drug was eluted from each filter (purified water) and analyzed by UV spectrophotometry at 276 nm. Analysis of variance [general linear model (GLM) multivariate] was performed using the linear model of multiple variables, significance at p < 0.05. RESULTS: Albuterol (in micrograms, mean ± standard deviation) delivered was higher with VMN placed at the gas inlet of the humidifier with each mode of ventilation (p < 0.01). APRVs has the highest albuterol delivery followed by PCV, PCVBF6, and APRV (1706.2 ± 60.9 µg vs. 1490.6 ± 61.1 µg vs. 1182.3 ± 61.4 µg vs. 1153.1 ± 99.7 µg, respectively, p < 0.001). The minute volume was positively correlated with the inhaled albuterol dose. CONCLUSIONS: Spontaneous breathing increased the albuterol delivery during APRV, compared with APRV alone and PCV modes. Placing the nebulizer proximal to the ventilator was more efficient for all modes tested.

11.
Respir Res ; 19(1): 254, 2018 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-30547791

RESUMO

BACKGROUND: Pulmonary arterial hypertension (PAH) is related to inflammation, and the lncRNA H19 is associated with inflammation. However, whether PDGF-BB-H19-let-7b-AT1R axis contributes to the pathogenesis of PAH has not been thoroughly elucidated to date. This study investigated the role of H19 in PAH and its related mechanism. METHODS: In the present study, SD rats, C57/BL6 mice and H19-/- mice were injected with monocrotaline (MCT) to establish a PAH model. H19 was detected in the cytokine-stimulated pulmonary arterial smooth muscle cells (PASMCs), serum and lungs of rats/mice. H19 overexpression and knockdown experiments were also conducted. A dual luciferase reporter assay was used to explore whether let-7b is a sponge miRNA of H19, and AT1R is a novel target of let-7b. A CCK-8 assay and flow cytometry were used to analyse cell proliferation. RESULTS: The results showed that H19 was highly expressed in the serum and lungs of MCT-induced rats/mice, and H19 was upregulated by PDGF-BB in vitro. H19 upregulated AT1R expression via sponging miRNA let-7b following PDGF-BB stimulation. AT1R is a novel target of let-7b. Moreover, the overexpression of H19 and AT1R could facilitate PASMCs proliferation in vitro. H19 knockout protected mice from pulmonary artery remodeling and PAH following MCT treatment. CONCLUSION: Our study showed that H19 is highly expressed in MCT-induced rodent lungs and upregulated by PDGF-BB. The H19-let-7b-AT1R axis contributed to the pathogenesis of PAH by stimulating PASMCs proliferation. The H19 knockout had a protective role in the development of PAH. H19 may be a potential tar-get for the treatment of PAH.


Assuntos
Hipertensão Pulmonar/metabolismo , MicroRNAs/biossíntese , Monocrotalina/toxicidade , Miócitos de Músculo Liso/metabolismo , RNA Longo não Codificante/biossíntese , Receptores de Angiotensina/biossíntese , Indutores da Angiogênese/farmacologia , Animais , Becaplermina/farmacologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Hipertensão Pulmonar/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miócitos de Músculo Liso/efeitos dos fármacos , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , RNA Longo não Codificante/agonistas , Ratos , Ratos Sprague-Dawley
12.
Oncoimmunology ; 7(10): e1494677, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30288364

RESUMO

Tobacco smoking causes DNA damages in epithelial cells and immune dysfunction in the lung, which collectively contribute to lung carcinogenesis and progression. However, potential mechanisms by which tumor-infiltrating immune cells contribute to lung cancer survival and their differential contributions in ever-smokers and never-smokers are not well studied. Here, we performed integrative analysis of 11 lung cancer gene-expression datasets, including 1,111 lung adenocarcinomas and 200 adjacent normal lung samples. Distinct pathways were altered in lung carcinogenesis in ever-smokers and never-smokers. Never-smoker patients had a better outcome than ever-smoker patients. We characterized compositional patterns of 21 types of immune cells in lung adenocarcinomas and revealed the complex association between immune cell composition and clinical outcomes. Interestingly, we found two subsets of immune cells, mast cells and CD4+ memory T cells, which had completely opposite associations with outcomes in resting and activated status. We further discovered that several chemokines and their associated receptors (e.g., CXCL11-CX3CR1 axis) were selectively altered in lung tumors in response to cigarette smoking and their abundances showed stronger correlation with fractions of these immune subsets in ever-smokers than never-smokers. The status switched from the resting to activated forms in mast cells and CD4+ memory T cells might manifest some important processes induced by cigarette smoking during tumor development and progression. Our findings suggested that aberrant activation of mast cells and CD4+ memory T cells plays crucial roles in cigarette smoking-induced immune dysfunction in the lung, which contributes to tumor development and progression.

13.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 47(2): 207-212, 2018 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-30226318

RESUMO

Pulmonary arterial hypertension (PAH) is a multi-etiological chronic disease characterized by a progressive elevation in pulmonary resistance and vascular remodeling. Its pathogenesis is complicated. Recently, emerging researches suggest that autophagy, as a self-protection mechanism maintaining the intracellular environment homeostasis in eukaryotes, participate in the occurrence and development of various types of PAH. Autophagy can regulate the survival, apoptosis of pulmonary vascular wall cells and secretion of vasoactive substances and inflammatory cytokines, thus influencing pulmonary vascular homeostasis. Some drugs based on regulating autophagy activity can effectively improve the prognosis of PAH. In this article, the regulatory role of autophagy on the development of pulmonary hypertension is reviewed to provide insight into PAH and its treatment.


Assuntos
Autofagia , Humanos , Hipertensão Pulmonar , Pulmão , Artéria Pulmonar
14.
J Breath Res ; 12(4): 046013, 2018 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-30102249

RESUMO

Lung cancer (LC) is a leading cause of cancer-related morbidity and mortality globally, and exhaled breath testing has been considered as a fast, convenient and non-invasive way to diagnose LC in its early stages. Volatile organic compounds (VOCs), as markers of LC in exhaled breath, have been widely investigated for cancer diagnosis. However, few studies have reported on the interference of benign pulmonary diseases (BPD) in the selection of VOC markers for LC. During this study, 207 samples were analyzed using thermal desorption instrumentation/gas chromatography/mass spectrometry (TD-GCMS) to detect C6-C30 VOCs, and all samples were divided into four groups: LC group, BPD group, lung disease (LD) group (including LC group and BPD group) and healthy group. To make up for the deficiency of detecting low carbon hydrocarbons (

Assuntos
Biomarcadores Tumorais/análise , Pneumopatias/diagnóstico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Compostos Orgânicos Voláteis/análise , Líquidos Corporais/química , Testes Respiratórios , Estudos de Casos e Controles , Expiração , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Microextração em Fase Sólida
15.
Am J Transl Res ; 9(11): 5116-5126, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29218109

RESUMO

OBJECTIVE: This study works to develop novel models that may be adopted for earlier non-invasive breathomics tests to determine pneumonia pathogens. METHODS: Two types of pneumonia models were created, both in vitro and in vivo. Paraneoplasm lung tissue and specific pathogen-free (SPF) rabbits were adopted and separately challenged with sterile saline solution control or three pathogens: Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. After inoculation, headspace air or exhaled air were absorbed by solid phase micro-extraction (SPME) fibers and subsequently analyzed with gas chromatograph Mass Spectrometer (GCMS). RESULTS: Pneumonia and pathogen-specific discriminating VOC patterns (1H-Pyrrole-3-carbonitrile, Diethyl phthalate, Cedrol, Decanoic acid, Cyclohexane, Diisooctyl phthalate) were determined. CONCLUSION: Our study successfully generated nosocomial pneumonia models for pneumonia diagnosis and pathogen-discriminating breath tests. The tests may allow for earlier pneumonia and pathogen diagnoses, and may transfer empirical therapy to targeted therapy earlier, thus improving clinical outcomes.

16.
Medicine (Baltimore) ; 96(46): e8716, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29145311

RESUMO

BACKGROUND: Mitochondrial diseases are a group of multisystem heterogeneous diseases caused by pathologic dysfunction of the mitochondrial respiratory chain. A wide range of clinical expression has been described. However, pulmonary hypertension has rarely been described in association with mitochondrial disease until the past decade, and there is no currently recognized treatment for the pulmonary hypertension complicated with mitochondrial disorder. PATIENT CONCERNS: We reported the case of a 15-year-old boy who presented with shortness of breath and exercise limitation after a cold, and the diagnosis of pulmonary hypertension was confirmed by right heart catheter. Other examinations, such as blood tests, high- resolution chest computed tomography scan, and pulmonary function test, excluded other associated diseases as causes of pulmonary hypertension. DIAGNOSES AND OUTCOMES: The initial diagnosis was idiopathic pulmonary arterial hypertension and an injection of vasodilator (Treprostinil) was given. However, the dyspnea and fatigue subsequently got worsened. Tracing back his family history, together with the electromyography, nerve conduction studies, and the result of muscle biopsy, mitochondrial disease was confirmed. After treatment with vitamin E, vitamin B2, ATP, and coenzyme Q10, the patient's condition improved. CONCLUSION: Pulmonary hypertension should be considered as another potential manifestation of mitochondrial disease. Both mechanism and treatment for pulmonary hypertension complicated with mitochondrial disease are unclear. Further study is necessary.


Assuntos
Hipertensão Pulmonar/etiologia , Doenças Mitocondriais/complicações , Doenças Mitocondriais/diagnóstico , Adolescente , Humanos , Masculino
17.
Int J Chron Obstruct Pulmon Dis ; 12: 1775-1780, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28684903

RESUMO

OBJECTIVE: The purpose of this study was to explore the insulin-like growth factor binding protein 7 (IGFBP7) level in the serum of chronic obstructive pulmonary disease (COPD) patients during acute exacerbation (AE). METHODS: The study population consisted of 47 AECOPD patients, including 25 patients enrolled between January 2011 and February 2011 (the first group) and 22 patients enrolled from December 2011 to August 2012 (the second group) and 29 healthy controls. Chemiluminescence-linked immunoassay was used to detect serum IGFBP7 levels. For the second group patients, IGFBP7 and C-reactive protein (CRP) levels were measured both on the admission day and on the discharge day. RESULTS: Among the first group AECOPD patients, serum IGFBP7 levels were significantly elevated in AECOPD patients in the intensive care unit (ICU; 52.92±16.32 ng/mL), and in hospitalized AECOPD patients not in ICU (40.66±13.9), compared to healthy subjects (30.3±7.09 ng/mL; P<0.01). For the second group AECOPD patients, the increased IGFBP7 levels reduced after the patients had recovered (34.42±11.88 vs 27.24±7.2 ng/mL; P<0.01). During AE, the correlation coefficient between IGFBP7 and CRP was 0.357. In receiver operating characteristic analysis, the area under the curve was 0.799 for CRP, and 0.663 for IGFBP7 in distinguishing patients with AECOPD on the admission day from the discharge day. CONCLUSION: Serum IGFBP7 levels were raised during AECOPD. Similar to the expression pattern of CRP, the IGFBP7 levels reduced after convalescence, suggesting that IGFBP7 might have a candidate role as a biomarker of AECOPD. No significant linear correlation was detected between IGFBP7 and CRP, indicating the probable different role for the two molecules in assessing AECOPD. Further study is needed to explore the value of IGFBP7 in differentiating phenotypes of AECOPD.


Assuntos
Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Doença Pulmonar Obstrutiva Crônica/sangue , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Imunoensaio , Pulmão/fisiopatologia , Masculino , Admissão do Paciente , Alta do Paciente , Valor Preditivo dos Testes , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Curva ROC , Reprodutibilidade dos Testes , Fatores de Tempo , Regulação para Cima
18.
Biomed Res Int ; 2017: 6516791, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28484717

RESUMO

Pulmonary thromboembolism (PTE) is part of a larger clinicopathological entity, venous thromboembolism. It is also a complex, multifactorial disorder divided into four major disease processes including venous thrombosis, thrombus in transit, acute pulmonary embolism, and pulmonary circulation reconstruction. Even when treated, some patients develop chronic thromboembolic pulmonary hypertension. PTE is also a common fatal type of pulmonary vascular disease worldwide, but earlier studies primarily focused on the pathological changes in the blood component of the disease. With contemporary advances in molecular and cellular biology, people are becoming increasingly aware of coagulation pathways, the function of vascular smooth muscle cells, microparticles, and the inflammatory pathways that play key roles in PTE. Combined hypoxia and immune research has revealed that PTE should be regarded as a class of complex diseases caused by multiple factors involving the vascular microenvironment and vascular cell dysfunction.


Assuntos
Pesquisa Biomédica/tendências , Hipertensão Pulmonar , Pulmão , Embolia Pulmonar , Fluxo Sanguíneo Regional , Animais , Humanos , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Pulmão/irrigação sanguínea , Pulmão/metabolismo , Pulmão/patologia , Pulmão/fisiopatologia , Embolia Pulmonar/metabolismo , Embolia Pulmonar/parasitologia , Embolia Pulmonar/fisiopatologia
19.
Environ Pollut ; 224: 310-316, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28222977

RESUMO

BACKGROUND: The association between ambient temperature and mortality has been well documented worldwide. However, limited data are available on nonfatal health outcomes, such as emergency department visits (EDVs), particularly from China. OBJECTIVES: To examine the temperature-EDV association in 12 Chinese cities; and to assess the modification effects by region, gender and age. METHODS: Daily meteorological data and non-accidental EDVs were collected during 2011-2014. Poisson regression with distributed lag non-linear model was applied to examine the temperature-lag-EDV association in each city. The effect estimates were pooled using multivariate meta-analysis at the national and regional level. Stratified analyses were performed by gender and age-groups. Sensitivity analyses adjusting for air pollution and relative humidity were conducted. RESULTS: A total of 4,443,127 EDVs were collected from the 12 cities. Both cold and hot temperatures were associated with increased risk of EDVs, with minimum-mortality temperature located at 64th percentile of temperature. The effect of cold temperature appeared on day 2 and persisted until day 30, causing a cumulative relative risk (RR) of 1.80 (1.54, 2.11). The effect of hot temperature appeared immediately and lasted until day 3, with a cumulative RR of 1.15 (1.03, 1.29). The effect of temperature on EDVs was similar in male and female but was attenuated with increasing age. The effect of cold temperature on EDVs was greater in southern areas of the country whereas the hot effect was greater in northern cities. The association was robust to a large range of sensitivity analyses. CONCLUSIONS: In China, there is a U-shaped association between temperature and risk of EDVs that is independent of air pollution and humidity. The temperature-EDV association varies with latitude and age-groups but is not affected by gender. Forecasting models for hospital emergency departments may be improved if temperature is included as an independent predictor.


Assuntos
Atmosfera , Cidades/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Temperatura Ambiente , Distribuição por Idade , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/estatística & dados numéricos , China , Exposição Ambiental/efeitos adversos , Exposição Ambiental/estatística & dados numéricos , Humanos , Umidade , Dinâmica não Linear , Ozônio/análise , Material Particulado/efeitos adversos , Material Particulado/análise , Fatores Sexuais , Fatores de Tempo
20.
Clin Chim Acta ; 466: 172-177, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28104361

RESUMO

The insulin-like growth factor-1 receptor (IGF-1R) is a central component of lung cancer signal transduction pathways. A phase III study failed for carboplatin, paclitaxel, with or without figitumumab in first-line treating metastatic non-small cell lung cancer (NSCLC). There is an urgent need for a better understanding of signaling in IGF system. Insulin-like growth factor-binding proteins (IGFBPs) function as modulators for IGF signaling through sequestration of IGFs in serum and the extracellular fluid. IGFBPs can also act as transporters or modulators for IGF action and insulin action. IGFBPs have attracted increased attention for their lung cancer-related role in recent years. Recent studies have demonstrated the critical role of IGFBPs in risk assessment, early detection, prognosis evaluation, and drug resistance appraisal for lung cancer. These observations suggest a potential new approach to understand the pathogenesis of lung cancer, have important clinical implications, while additional investigations are necessary.


Assuntos
Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Neoplasias Pulmonares/metabolismo , Humanos , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/antagonistas & inibidores , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Terapia de Alvo Molecular/métodos , Receptor IGF Tipo 1/metabolismo , Transdução de Sinais/fisiologia
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