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1.
BMC Pulm Med ; 21(1): 348, 2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34742287

RESUMO

BACKGROUND: High-throughput next-generation sequencing (HT-NGS) has the potential to detect a large variety of pathogens; however, the application of HT-NGS in lung transplant (LTx) recipients remains limited. We aimed to evaluate the value of HT-NGS for pathogen detection and diagnosis of pulmonary infection during early-stage post-lung transplantation. METHODS: In this retrospective study, we enrolled 51 LTx recipients who underwent lung transplantation between January 2020 and December 2020. Bronchoalveolar lavage fluid (BALF) samples were collected for the detection of pathogens using both HT-NGS and conventional microbiological testing. The detection of pathogens and diagnostic performance of HT-NGS were compared with that of conventional methods. RESULTS: HT-NGS provided a higher positive rate of pathogen detection than conventional microbiological testing (88.24% vs. 76.47%). The most common bacteria detected via HT-NGS during early-stage post-lung transplantation were Enterococcus, Staphylococcus, Pseudomonas and Klebsiella, while all fungi were Candida and all viruses were Herpesvirus. Uncommon pathogens, including Strongyloides, Legionella, and Mycobacterium abscesses were identified by HT-NGS. The sensitivity of HT-NGS for diagnosing pulmonary infection was significantly higher than that of conventional microbiological testing (97.14% vs. 68.57%; P < 0.001). For three LTx recipients, treatment regimens were adjusted according to the results of HT-NGS, leading to a complete recovery. CONCLUSION: HT-NGS is a highly sensitive technique for pathogen detection, which may provide diagnostic advantages, especially in LTx recipients, contributing to the optimization of treatment regimens against pulmonary infection during early-stage post-lung transplantation.

3.
Ann Transl Med ; 9(11): 941, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34350256

RESUMO

Background: Risk of adverse outcomes in COVID-19 patients by stratifying by the time from symptom onset to confirmed diagnosis status is still uncertain. Methods: We included 1,590 hospitalized COVID-19 patients confirmed by real-time RT-PCR assay or high-throughput sequencing of pharyngeal and nasal swab specimens from 575 hospitals across China between 11 December 2019 and 31 January 2020. Times from symptom onset to confirmed diagnosis, from symptom onset to first medical visit and from first medical visit to confirmed diagnosis were described and turned into binary variables by the maximally selected rank statistics method. Then, survival analysis, including a log-rank test, Cox regression, and conditional inference tree (CTREE) was conducted, regarding whether patients progressed to a severe disease level during the observational period (assessed as severe pneumonia according to the Chinese Expert Consensus on Clinical Practice for Emergency Severe Pneumonia, admission to an intensive care unit, administration of invasive ventilation, or death) as the prognosis outcome, the dependent variable. Independent factors included whether the time from symptom onset to confirmed diagnosis was longer than 5 days (the exposure) and other demographic and clinical factors as multivariate adjustments. The clinical characteristics of the patients with different times from symptom onset to confirmed diagnosis were also compared. Results: The medians of the times from symptom onset to confirmed diagnosis, from symptom onset to first medical visit, and from first medical visit to confirmed diagnosis were 6, 3, and 2 days. After adjusting for age, sex, smoking status, and comorbidity status, age [hazard ratio (HR): 1.03; 95% CI: 1.01-1.04], comorbidity (HR: 1.84; 95% CI: 1.23-2.73), and a duration from symptom onset to confirmed diagnosis of >5 days (HR: 1.69; 95% CI: 1.10-2.60) were independent predictors of COVID-19 prognosis, which echoed the CTREE models, with significant nodes such as time from symptom onset to confirmed diagnosis, age, and comorbidities. Males, older patients with symptoms such as dry cough/productive cough/shortness of breath, and prior COPD were observed more often in the patients who procrastinated before initiating the first medical consultation. Conclusions: A longer time from symptom onset to confirmed diagnosis yielded a worse COVID-19 prognosis.

5.
J Allergy Clin Immunol Pract ; 9(7): 2645-2655.e14, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33684635

RESUMO

BACKGROUND: Chronic respiratory diseases (CRD) are common among patients with coronavirus disease 2019 (COVID-19). OBJECTIVES: We sought to determine the association between CRD (including disease overlap) and the clinical outcomes of COVID-19. METHODS: Data of diagnoses, comorbidities, medications, laboratory results, and clinical outcomes were extracted from the national COVID-19 reporting system. CRD was diagnosed based on International Classification of Diseases-10 codes. The primary endpoint was the composite outcome of needing invasive ventilation, admission to intensive care unit, or death within 30 days after hospitalization. The secondary endpoint was death within 30 days after hospitalization. RESULTS: We included 39,420 laboratory-confirmed patients from the electronic medical records as of May 6, 2020. Any CRD and CRD overlap was present in 2.8% and 0.2% of patients, respectively. Chronic obstructive pulmonary disease (COPD) was most common (56.6%), followed by bronchiectasis (27.9%) and asthma (21.7%). COPD-bronchiectasis overlap was the most common combination (50.7%), followed by COPD-asthma (36.2%) and asthma-bronchiectasis overlap (15.9%). After adjustment for age, sex, and other systemic comorbidities, patients with COPD (odds ratio [OR]: 1.71, 95% confidence interval [CI]: 1.44-2.03) and asthma (OR: 1.45, 95% CI: 1.05-1.98), but not bronchiectasis, were more likely to reach to the composite endpoint compared with those without at day 30 after hospitalization. Patients with CRD were not associated with a greater likelihood of dying from COVID-19 compared with those without. Patients with CRD overlap did not have a greater risk of reaching the composite endpoint compared with those without. CONCLUSION: CRD was associated with the risk of reaching the composite endpoint, but not death, of COVID-19.


Assuntos
Asma , COVID-19 , Doença Pulmonar Obstrutiva Crônica , Asma/epidemiologia , Comorbidade , Hospitalização , Humanos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2
6.
Hum Cell ; 34(2): 468-477, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33128699

RESUMO

Lung cancer is the most affected malignant tumor in the world, and its specific pathogenesis is still unclear. It has been confirmed that circ0001320 is down-regulated in lung cancer, but its mechanism has not been reported. Further study found that circ0001320 was down-regulated in lung cancer cells, localized in the cytoplasm, and had multiple miR-558 binding sites. Dual-luciferase reporter gene assay, RNA-pull-down, and immunoprecipitation experiments all confirmed that circ0001320 directly bound to miR-558, and then inhibit the expression of miR-558. MiR-558 was up-regulated in lung cancer cells, and bound the downstream target genes TNFAIP1 and TPM1 to inhibit their expression. Western blot showed that circ0001320 significantly up-regulated the protein levels of TNFAIP1 and TPM1, while miR-558 blocked this effect of circ0001320. Circ0001320, TNFAIP1, and TPM1 all inhibited the proliferation and invasion of lung cancer cells and promoted apoptosis, while miR-558 had the opposite effects. After transfection with circ0001320 overexpression vector, miR-558 up-regulation or down-regulation of TNFAIP1, or TPM1 expression significantly reversed the inhibition of cell growth and invasion by circ0001320. Similarly, the expression of TNFAIP1 or TPM1 was down-regulated, while miR-558 expression was inhibited, and the levels of cell proliferation, apoptosis, and invasion did not change significantly. Therefore, these fully show that circ0001320 inhibits the growth and invasion of lung cancer cells through miR-558/TNFAIP1 and TPM1 pathways, which may be closely related markers and therapeutic targets of lung cancer.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Expressão Gênica/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo , Invasividade Neoplásica/genética , RNA Circular/genética , RNA Circular/farmacologia , Tropomiosina/genética , Tropomiosina/metabolismo , Adenocarcinoma/terapia , Apoptose/genética , Carcinoma de Células Escamosas/terapia , Humanos , Neoplasias Pulmonares/terapia , Terapia de Alvo Molecular , Ligação Proteica/genética , RNA Circular/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Células Tumorais Cultivadas
7.
Invest New Drugs ; 39(2): 477-487, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33052556

RESUMO

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are recommended first-line treatments in EGFR-mutated (EGFRm) non-small-cell lung cancer (NSCLC). However, acquired resistance (e.g. MET amplification) is frequently observed. Savolitinib (volitinib, HMPL-504, AZD6094) is an oral, potent, and highly selective MET-TKI. In this phase Ib, open-label, multicenter study, we enrolled Chinese patients with EGFRm advanced NSCLC, whose disease progressed following prior EGFR-TKI treatment. In the safety run-in, patients received savolitinib 600 or 800 mg plus gefitinib 250 mg orally once daily, and dose-limiting toxicities were recorded. In the expansion phase, patients with MET amplification received savolitinib plus gefitinib. The primary endpoint was safety/tolerability. Secondary endpoints included antitumor activity. Thirteen patients were enrolled in the safety phase (median age 52 years, 46% female) and 51 enrolled in the expansion phase (median age 61 years, 67% female). No dose-limiting toxicities were reported in either dose group during the safety run-in. Adverse events of grade ≥ 3 in the safety run-in and expansion phases (n = 57) were reported in 21 (37%) patients. The most frequently reported adverse events (all grades) were: vomiting (n = 26, 46%), nausea (n = 23, 40%), increased aspartate aminotransferase (n = 22, 39%). Of four deaths, none were treatment-related. The objective response rates in EGFR T790M-negative, -positive, and -unknown patients were 52% (12/23), 9% (2/23), and 40% (2/5), respectively. Savolitinib 600 mg plus gefitinib 250 mg once daily had an acceptable safety profile and demonstrated promising antitumor activity in EGFRm, MET-amplified advanced NSCLC patients who had disease progression on EGFR-TKIs. NCT02374645, Date of registration: March 2nd 2015.

8.
J Thorac Dis ; 12(10): 6132-6135, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33209449
10.
Biochem Biophys Res Commun ; 532(4): 598-604, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-32900484

RESUMO

OBJECTIVE: Pulmonary fibrosis is a fatal interstitial lung disease that is characterized by excessive accumulation of extracellular matrix (ECM) and remodeling of lung. The precise mechanisms underlying pulmonary fibrosis still remain unclear. In the current study, we aimed to investigate the alteration and function of serine (or cysteine) peptidase inhibitor, clade A, member 3 N (Serpina3n) in pulmonary fibrotic models and explore the potential mechanisms. METHODS: We induced pulmonary fibrosis in mice by silica and bleomycin respectively and determined Serpina3n in lung tissues, and then verified the expression of Serpina3n and its correlation with pulmonary fibrosis at seven time points in a bleomycin longstanding model. Moreover, adeno-associated virus type 9 (AAV9)-mediated Serpina3n knockdown was used to treat pulmonary fibrosis in the bleomycin model, whose possible mechanisms would be preliminarily explored by detecting chymotrypsin C as an example. RESULTS: Serpina3n was up-regulated significantly in lungs of both models at mRNA and protein levels relative to control. Notably, the expression of Serpina3n peaked during the 3rd week and then decreased until nearly normal levels during the 10th week, which was closely related to fibrotic procession in bleomycin-treated mice. AAV-mediated Serpina3n knockdown in the lung tissues alleviated bleomycin-induced fibrotic symptoms at various levels and disinhibit chymotrypsin C. CONCLUSIONS: Our study revealed that Serpina3n is a critical regulator in pulmonary fibrosis and suggested Serpina3n inhibition as a potential therapeutic strategy in chronic pulmonary injuries.


Assuntos
Proteínas de Fase Aguda/fisiologia , Fibrose Pulmonar/metabolismo , Serpinas/fisiologia , Proteínas de Fase Aguda/genética , Proteínas de Fase Aguda/metabolismo , Animais , Bleomicina , Quimotripsina/metabolismo , Técnicas de Silenciamento de Genes , Camundongos , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/enzimologia , Fibrose Pulmonar/patologia , Serpinas/genética , Serpinas/metabolismo , Regulação para Cima
11.
Chronic Dis Transl Med ; 6(2): 87-97, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32363045

RESUMO

Since December 2019, increasing attention has been paid to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Wuhan, China. SARS-CoV-2 primarily invades the respiratory tract and lungs, leading to pneumonia and other systemic disorders. The effect of SARS-CoV-2 in transplant recipients has raised significant concerns, especially because there is a large population of transplant recipients in China. Based on the current epidemic situation, this study reviewed publications on this virus and coronavirus disease 2019 (COVID-19), analyzed common features of respiratory viral pneumonias, and presented the currently reported clinical characteristics of COVID-19 in transplant recipients to improve strategies regarding the diagnosis and treatment of COVID-19 in this special population.

12.
Chin Med J (Engl) ; 133(12): 1390-1396, 2020 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-32251003

RESUMO

BACKGROUND: Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients. METHODS: From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores. RESULTS: Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation. CONCLUSIONS: LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Transplante de Pulmão/métodos , Pneumonia Viral/complicações , Fibrose Pulmonar/cirurgia , Síndrome do Desconforto Respiratório/cirurgia , Idoso , COVID-19 , Infecções por Coronavirus/mortalidade , Oxigenação por Membrana Extracorpórea , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Fibrose Pulmonar/mortalidade , Síndrome do Desconforto Respiratório/mortalidade , SARS-CoV-2
13.
Eur Respir J ; 55(6)2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32269086

RESUMO

BACKGROUND: During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in other parts of China have been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences. METHODS: Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients within and outside Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicentre as well the administrative centre of Hubei province) and the duration between symptom onset and admission on prognosis were also determined. RESULTS: At the data cut-off (31 January 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597 (92.3%) out of 647) were older (mean age 49.7 versus 44.9 years), had more cases with comorbidity (32.9% versus 19.7%), higher symptomatic burden, abnormal radiologic manifestations and, especially, a longer waiting time between symptom onset and admission (5.7 versus 4.5 days) compared with patients outside Hubei. Patients in Hubei (severe event rate 23.0% versus 11.1%, death rate 7.3% versus 0.3%, HR (95% CI) for critical illness 1.59 (1.05-2.41)) have a poorer prognosis compared with patients outside Hubei after adjusting for age and comorbidity. However, among patients outside Hubei, the duration from symptom onset to hospitalisation (mean 4.4 versus 4.7 days) and prognosis (HR (95%) 0.84 (0.40-1.80)) were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR (95%) 1.05 (1.01-1.08)). CONCLUSION: There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicentre. Future studies to determine the reason for delaying hospitalisation are warranted.


Assuntos
Infecções por Coronavirus/mortalidade , Hospitalização , Pneumonia Viral/mortalidade , Adulto , Idoso , Betacoronavirus , COVID-19 , Doenças Cardiovasculares/epidemiologia , China , Estudos de Coortes , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico por imagem , Tosse/etiologia , Diabetes Mellitus/epidemiologia , Surtos de Doenças , Dispneia/etiologia , Fadiga/etiologia , Feminino , Febre/etiologia , Geografia , Humanos , Hipertensão/epidemiologia , Unidades de Terapia Intensiva/estatística & dados numéricos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pandemias , Faringite/etiologia , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico por imagem , Prognóstico , Modelos de Riscos Proporcionais , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença , Fatores de Tempo , Tempo para o Tratamento/estatística & dados numéricos , Tomografia Computadorizada por Raios X
14.
J Thorac Dis ; 12(3): 830-838, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32274150

RESUMO

Background: Diabetes mellitus is a recognized risk factor for esophageal squamous cell carcinomas (ESCC), and metformin is a recognized protective factor for some gastrointestinal tumors. But knowledge is limited regarding the effect of metformin on survival outcome of ESCC patients with type 2 diabetes mellitus (T2DM). We assessed the impact of post-diagnosis metformin use on overall survival (OS) and disease-free survival (DFS) in ESCC with T2DM undergoing surgical resection. Methods: A retrospective analysis was performed on 3,523 patients with ESCC who met the study conditions after surgical resection. Log-rank and Cox regression models were used to evaluate the relationship between metformin and T2DM and ESCC survival rate, and adjusted according to age, gender, BMI, smoking, drinking and staging, et al. Results: Among included ESCC patients, 619 were associated with type 2 diabetes, while the remaining 2,904 were not associated with type 2 diabetes. The 5-year OS (28.43%) of patients with T2DM was significantly lower than that of patients without T2DM (32.75%), P=0.037. DFS in 5 years were 27.30% (with T2DM) and 31.75% (without T2DM) (P=0.030), respectively. Compared with patients without T2DM, patients with T2DM presented worse OS [adjusted risk ratio (HRadj) =1.19] and DFS (HRadj =1.17; P<0.001). Among the 619 patients with type 2 diabetes, 485 were treated with metformin and 134 were not treated with metformin. Patients treated with metformin had significantly improved OS [adjusted risk ratio (HRadj) =0.89; P=0.031) and DFS (HRadj =0.90; P=0.013). Conclusions: T2DM was again associated with poorer survival in ESCC patients, and metformin may improve the prognosis of these patients.

16.
Eur Respir J ; 55(5)2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32217650

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak is evolving rapidly worldwide. OBJECTIVE: To evaluate the risk of serious adverse outcomes in patients with COVID-19 by stratifying the comorbidity status. METHODS: We analysed data from 1590 laboratory confirmed hospitalised patients from 575 hospitals in 31 provinces/autonomous regions/provincial municipalities across mainland China between 11 December 2019 and 31 January 2020. We analysed the composite end-points, which consisted of admission to an intensive care unit, invasive ventilation or death. The risk of reaching the composite end-points was compared according to the presence and number of comorbidities. RESULTS: The mean age was 48.9 years and 686 (42.7%) patients were female. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached the composite end-points. 399 (25.1%) reported having at least one comorbidity. The most prevalent comorbidity was hypertension (16.9%), followed by diabetes (8.2%). 130 (8.2%) patients reported having two or more comorbidities. After adjusting for age and smoking status, COPD (HR (95% CI) 2.681 (1.424-5.048)), diabetes (1.59 (1.03-2.45)), hypertension (1.58 (1.07-2.32)) and malignancy (3.50 (1.60-7.64)) were risk factors of reaching the composite end-points. The hazard ratio (95% CI) was 1.79 (1.16-2.77) among patients with at least one comorbidity and 2.59 (1.61-4.17) among patients with two or more comorbidities. CONCLUSION: Among laboratory confirmed cases of COVID-19, patients with any comorbidity yielded poorer clinical outcomes than those without. A greater number of comorbidities also correlated with poorer clinical outcomes.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Adulto , COVID-19 , China/epidemiologia , Comorbidade , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Prognóstico , Fatores de Risco , SARS-CoV-2
17.
Mol Genet Genomic Med ; 8(5): e1195, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32130794

RESUMO

BACKGROUND: This study is aimed to unravel the genetic factors associated with microRNA (miRNA) expression in regulating sex-determining region Y-box 2 (SOX2)-mediated cisplatin resistance in small-cell lung cancer (SCLC). METHODS: The relevance of SOX2 expression in SCLC was analyzed in a panel of SCLC cells by quantitative real-time PCR (qPCR) and western blot (WB). We selected DMS114 cell line, in which SOX2 was amplified via lentiviral vector-mediated transfection of the SOX2 genes and tested for the half-maximal inhibitory concentration (IC50 ) by MTS assay. High-throughput sequencing and screening of differentially expressed miRNAs between SOX2-overexpressing and normal control cells were performed. Finally, miRanda software was used to verify the miRNAs bound with SOX2 and qPCR was used to identify the expression of miRNAs which were binding with SOX2. RESULTS: Cisplatin-resistant SOX2-overexpressing DMS114 cell lines were successfully developed, showing a statistically significant increase in SOX2 expression by qPCR and WB. Our results showed a typically higher IC50 value in SOX2-overexpressing cells compared with the negative controls. The high-throughput sequencing analysis revealed that 68 miRNAs were upregulated and 24 miRNAs were downregulated in the SOX2-overexpressing cells. The 24 downregulated miRNAs were further verified. Of them, a cancer-related miRNA, hsa-miR-340-5p, showed a higher binding affinity with SOX2 in network regulation mapping, which was also found to be markedly downregulated under qPCR analysis. CONCLUSION: We demonstrated that downregulated expression of hsa-miR-340-5p may affect cisplatin resistance by mediating SOX2 expression in SCLC cells, which may provide a potential target for the therapy of chemoresistant SCLCs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/genética , MicroRNAs/genética , Fatores de Transcrição SOXB1/genética , Células A549 , Antineoplásicos/toxicidade , Cisplatino/toxicidade , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , Fatores de Transcrição SOXB1/metabolismo
18.
N Engl J Med ; 382(18): 1708-1720, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32109013

RESUMO

BACKGROUND: Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. METHODS: We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. RESULTS: The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. CONCLUSIONS: During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.).


Assuntos
Betacoronavirus , Infecções por Coronavirus , Surtos de Doenças , Pandemias , Pneumonia Viral , Adolescente , Adulto , Idoso , COVID-19 , Criança , China/epidemiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Feminino , Febre/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , SARS-CoV-2 , Adulto Jovem
19.
Chin Med J (Engl) ; 132(23): 2783-2789, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31856048

RESUMO

BACKGROUND: Lung transplantation (LT) has been demonstrated as the only effective therapy for patients with end-stage lung diseases. Increasing listed lung transplant candidates and expanding volumes of lung transplant centers across China require well-organized programs and registry data collection based on the large population. This study aimed to summarize and analyze the data of LT development in China. METHODS: We retrospectively collected and analyzed data from the China Lung Transplantation Registry (CLuTR). Key data were reported from the registry with transplant types, indications, donor and recipient characteristics, outcomes and survival. The survival <30 days, 1-year and 3-year survival rates were estimated with risk factors identified. RESULTS: CLuTR contained data from 1053 lung transplants performed through January 1st, 2015 to December 31st, 2018 reported by 18 registered transplant centers. The largest category of diagnosis before transplantation was idiopathic interstitial pneumonitis. The total <30 days, 1-year and 3-year survival rates in CLuTR were 81.45%, 70.11%, and 61.16% with discrepancy by indications. Large proportion of recipients who were more than 60 years old required higher standard of care. Infection-related complications resulted in more death events in the early post-surgery periods. New York Heart Association grading at listing, extra-corporeal membrane oxygenation usage peri-transplantation, allograft dysfunction (primary graft dysfunction >Grade 0), renal insufficiency (estimated glomerular filtration rate <60 mL·min·1.73 m), were independently associated with a higher risk for 3-year mortality in the entire cohort. CONCLUSIONS: Facing more end-stage of lung diseases and comorbidities, this study analyzed the outcomes and survival of LT recipients in China. Further prospectively stratified analyses with longer follow-up will be needed.


Assuntos
Transplante de Pulmão/estatística & dados numéricos , China , Sobrevivência de Enxerto , Humanos , Sistema de Registros , Estudos Retrospectivos , Taxa de Sobrevida
20.
J Thorac Dis ; 11(3): 686-693, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31019755

RESUMO

Background: The aim of this retrospective study was to assess the influence of the sequence of pulmonary vessel ligation during video-assisted thoracoscopic lobectomy on long-term survival in patients with non-small cell lung cancer (NSCLC). Methods: This retrospective study included 60 patients treated surgically with lobectomy and standard lymphadenectomy between 2012 and 2013. Patients had primary ligation of the pulmonary vein or veins (PV group, 33 patients) or of the pulmonary artery or arteries (PA group, 27 patients). Patients were excluded if they had undergone pulmonary wedge resection before lobectomy. Subgroup and sensitivity analyses were also used to investigate the effect of clinical characteristics of interest on survival. Results: Median follow-up was 54.5 months. Baseline characteristics of the two groups were statistically comparable regarding gender, histology, type of resection, T stage, and overall stage (all P>0.05). Overall, 5-year survival reached 66.67% in the PV group and 44.44% in the PA group (P=0.084). There were no differences between two groups regarding overall survival (OS) (P=0.063, HR: 2.093; 95% CI: 0.960-4.564), disease-free survival (DFS) (P=0.180, HR: 1.539; 95% CI: 0.820-2.889), or cancer-specific deaths (P=0.227, 14/33 vs. 17/27). Subgroup analyses showed no significant difference of OS (P=0.374, HR: 1.541; 95% CI: 0.594-3.997) or DFS (PLog-rank=0.746) for isolated adenocarcinoma, but significant differences in OS (PLog-Rank=0.036; HR: 3.992; 95% CI: 0.987-16.139) and DFS (P=0.044, HR: 3.011; 95% CI: 1.031-8.795) between the two groups of patients in whom squamous cell carcinomas. Sensitivity analysis showed that the differences were not statistically significant between the two groups regarding OS (P=0.140, HR: 1.944; 95% CI: 0.804-4.700) and DFS (P=0.190, HR: 1.605; 95% CI: 0.791-3.255) for patients with a tumour diameter of greater than 3 cm. Conclusions: In summary, the sequence of pulmonary vessel ligation during video-assisted thoracoscopic lobectomy for NSCLC has no different effects on long-term survival, but for patients with squamous cell carcinoma, venous ligation should be preferred first since it may bring survival advantage after surgery.

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