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1.
Crit Care ; 26(1): 109, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35428349

RESUMO

BACKGROUND: High-flow nasal cannula (HFNC) can improve ventilatory function in patients with acute COPD exacerbation. However, its effect on clinical outcomes remains uncertain. METHODS: This randomized controlled trial was conducted from July 2017 to December 2020 in 16 tertiary hospitals in China. Patients with acute COPD exacerbation with mild hypercapnia (pH ≥ 7.35 and arterial partial pressure of carbon dioxide > 45 mmHg) were randomly assigned to either HFNC or conventional oxygen therapy. The primary outcome was the proportion of patients who met the criteria for intubation during hospitalization. Secondary outcomes included treatment failure (intolerance and need for non-invasive or invasive ventilation), length of hospital stay, hospital cost, mortality, and readmission at day 90. RESULTS: Among 337 randomized patients (median age, 70.0 years; 280 men [83.1%]; median pH 7.399; arterial partial pressure of carbon dioxide 51 mmHg), 330 completed the trial. 4/158 patients on HFNC and 1/172 patient on conventional oxygen therapy met the criteria for intubation (P = 0.198). Patients progressed to NPPV in both groups were comparable (15 [9.5%] in the HFNC group vs. 22 [12.8%] in the conventional oxygen therapy group; P = 0.343). Compared with conventional oxygen therapy, HFNC yielded a significantly longer median length of hospital stay (9.0 [interquartile range, 7.0-13.0] vs. 8.0 [interquartile range, 7.0-11.0] days) and a higher median hospital cost (approximately $2298 [interquartile range, $1613-$3782] vs. $2005 [interquartile range, $1439-$2968]). There were no significant differences in other secondary outcomes between groups. CONCLUSIONS: In this multi-center randomized controlled study, HFNC compared to conventional oxygen therapy did not reduce need for intubation among acute COPD exacerbation patients with mild hypercapnia. The future studies should focus on patients with acute COPD exacerbation with respiratory acidosis (pH < 7.35). However, because the primary outcome rate was well below expected, the study was underpowered to show a meaningful difference between the two treatment groups. TRIAL REGISTRATION: NCT03003559 . Registered on December 28, 2016.


Assuntos
Ventilação não Invasiva , Doença Pulmonar Obstrutiva Crônica , Insuficiência Respiratória , Idoso , Cânula , Dióxido de Carbono , Feminino , Humanos , Hipercapnia/terapia , Masculino , Oxigênio , Oxigenoterapia , Insuficiência Respiratória/terapia
2.
Front Pharmacol ; 13: 829673, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35355710

RESUMO

Tissue remodeling/fibrosis is a main feature of idiopathic pulmonary fibrosis (IPF), which results in the replacement of normal lung parenchyma with a collagen-rich extracellular matrix produced by fibroblasts and myofibroblasts. Epithelial-mesenchymal transition (EMT) in type 2 lung epithelial cells is a key process in IPF, which leads to fibroblasts and myofibroblasts accumulation and excessive collagen deposition. DEC1, a structurally distinct class of basic helix-loop-helix proteins, is associated with EMT in cancer. However, the functional role of DEC1 in pulmonary fibrosis (PF) remains elusive. Herein, we aimed to explore DEC1 expression in IPF and bleomycin (BLM)-induced PF in mice and the mechanisms underlying the fibrogenic effect of DEC1 in PF in vivo and in vitro by Dec1-knockout (Dec1 -/-) mice, knockdown and overexpression of DEC1 in alveolar epithelial cells (A549 cells). We found that the expression of DEC1 was increased in IPF and BLM-injured mice. More importantly, Dec1 -/- mice had reduced PF after BLM challenge. Additionally, DEC1 deficiency relieved EMT development and repressed the PI3K/AKT/GSK-3ß/ß-catenin integrated signaling pathway in mice and in A549 cells, whereas DEC1 overexpression in vitro had converse effects. Moreover, the PI3K/AKT and Wnt/ß-catenin signaling inhibitors, LY294002 and XAV-939, ameliorated BLM-meditated PF in vivo and relieved EMT in vivo and in vitro. These pathways are interconnected by the GSK-3ß phosphorylation status. Our findings indicated that during PF progression, DEC1 played a key role in EMT via the PI3K/AKT/GSK-3ß/ß-catenin integrated signaling pathway. Consequently, targeting DEC1 may be a potential novel therapeutic approach for IPF.

3.
Cancer Med ; 2022 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-35332684

RESUMO

OBJECTIVES: To explore the diagnostic value of radiomics in differentiating between lung adenocarcinomas appearing as ground-glass opacity nodules (GGO) with high- and low Ki-67 expression levels. MATERIALS AND METHODS: From January 2018 to January 2021, patients with pulmonary GGO who received lung resection were evaluated for potential enrollment. The included GGOs were then randomly divided into a training cohort and a validation cohort with a ratio of 7:3. Logistic regression (LR), decision tree (DT), support vector machines (SVM), and adaboost (AB) were applied for radiomic model construction. Area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of the established models. RESULTS: Seven hundred and sixty-nine patients with 769 GGOs were included in this study. Two hundred and forty-five GGOs were confirmed to be of high Ki-67 labeling index (LI). In the training cohort, gender, age, spiculation sign, pleural indentation sign, bubble sign, and maximum 2D diameter of the nodule were found to be significantly different between high- and low Ki-67 LI groups (p < 0.05), and spiculation sign and maximum 2D diameter of the nodule were further confirmed to be risk factors for Ki-67 LI. The radiomic model established using SVM exhibited an AUC of 0.731 in the validation cohort, which was higher than that of the clinical-radiographic model (AUC = 0.675). Moreover, radiomic model combining both intra- and peri-nodular features showed better diagnostic efficacy than using intra-nodular features alone (AUC = 0.731 and 0.720, respectively). CONCLUSIONS: The established radiomic model exhibited good diagnostic efficacy in differentiating between lung adenocarcinoma GGOs with high and low Ki-67 LI, which was higher than the clinical-radiographic model. Peri-nodular radiomic features showed added benefits to the radiomic model. As a novel noninvasive method, radiomics have the potential to be applied in the preliminary classification of Ki-67 expression level in lung adenocarcinoma GGOs.

4.
Int J Infect Dis ; 117: 37-44, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35108608

RESUMO

OBJECTIVES: This study aimed to assess the current incidence and risk factors for polymyxin B-associated acute kidney injury (AKI) in Chinese hospitals for a more effective clinical use for polymyxin B. METHODS: This multicenter, retrospective cohort study included patients from 14 Chinese teaching hospitals who received polymyxin B therapy. Univariate and multivariate logistic regression models were used to determine the factors associated with polymyxin B-associated incident AKI. Furthermore, a multivariate logistic regression model was used to identify the independent risk factors for AKI. RESULTS: A total of 251 patients were included in the analysis. The overall incidence of AKI was 33.5%. A multivariate logistic regression model identified the loading dose (hazard ratio (HR), 1.84; 95% confidence interval (CI), 1.01-3.38; P = 0.0491) and the use of two or more nephrotoxic drugs (HR, 3.56; 95% CI, 1.55-8.18; P = 0.0029) as independent risk factors for the occurrence of AKI. Meanwhile, the estimated glomerular filtration rate had a protective effect (HR, 0.99; 95% CI, 0.98-0.99; P = 0.0006) on the occurrence of AKI. The daily dose, cumulative dose, and treatment duration of polymyxin B did not affect the occurrence of AKI. CONCLUSIONS: The use of polymyxin B loading doses and the combined use of multiple nephrotoxic drugs are independent risk factors for polymyxin B-associated AKI. The severity of AKI may be higher in patients with elevated baseline creatinine levels.


Assuntos
Injúria Renal Aguda , Polimixina B , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Antibacterianos/efeitos adversos , Humanos , Polimixina B/efeitos adversos , Estudos Retrospectivos , Fatores de Risco
5.
Signal Transduct Target Ther ; 6(1): 414, 2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-34873151

RESUMO

Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 µM, depending on viruses or cells, and selective index (SI) in 15-83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1-9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2-25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.


Assuntos
Antivirais/administração & dosagem , Azidas/administração & dosagem , COVID-19/tratamento farmacológico , Desoxicitidina/análogos & derivados , SARS-CoV-2/metabolismo , Timo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Coronavirus Humano OC43/metabolismo , Desoxicitidina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ratos , Timo/metabolismo , Timo/virologia
6.
Front Pharmacol ; 12: 683296, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539392

RESUMO

Background: In addition to supportive therapy, antiviral therapy is an effective treatment for coronavirus disease 2019 (COVID-19). Objective: To compare the efficacy and safety of favipiravir and umifenovir (Arbidol) to treat COVID-19 patients. Methods: We conducted a prospective, randomized, controlled, open-label multicenter trial involving adult patients with COVID-19. Enrolled patients with initial symptoms within 12 days were randomly assigned in a 1:1 ratio to receive conventional therapy plus Arbidol (200 mg*3/day) or favipiravir (1600 mg*2/first day followed by 600 mg*2/day) for 7 days. The primary outcome was the clinical recovery rate at day 7 of drug administration (relief for pyrexia and cough, respiratory frequency ≤24 times/min; oxygen saturation ≥98%). Latency to relief for pyrexia and cough and the rate of auxiliary oxygen therapy (AOT) or noninvasive mechanical ventilation (NMV)/mechanical ventilation (MV) were the secondary outcomes. Safety data were collected for 17 days. Results: A total of 240 enrolled COVID-19 patients underwent randomization; 120 patients were assigned to receive favipiravir (116 assessed), and 120 patients were assigned to receive Arbidol (120 assessed). The clinical recovery rate at day 7 of drug administration did not significantly differ between the favipiravir group (71/116) and Arbidol group (62/120) (p = 0.1396, difference in recovery rate: 0.0954; 95% CI: -0.0305∼0.2213). Favipiravir contributed to relief for both pyrexia (difference: 1.70 days, p < 0.0001) and cough (difference: 1.75 days, p < 0.0001). No difference was observed in the AOT or NMV/MV rate (both p > 0.05). The most frequently observed favipiravir-associated adverse event was increased serum uric acid (16/116, OR: 5.52, p = 0.0014). Conclusion: Among patients with COVID-19, favipiravir, compared to Arbidol, did not significantly improve the clinical recovery rate at day 7. Favipiravir significantly improved the latency to relieve pyrexia and cough. Adverse effects caused by favipiravir are mild and manageable.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34315392

RESUMO

BACKGROUND: Smoking participates in pathogenesis of lung cancer. Long non-coding RNAs (lncRNAs) play some specific roles during development of lung cancers. OBJECTIVE: To investigate effects of smoking on lncRNA alterations in lung cancer. METHODS: There are 522 lung adenocarcinoma (LUAD) and 504 lung squamous cell carcinoma (LUSC) participants. Clinical and lncRNA genetic data were downloaded from The Cancer Genome Atlas (TCGA) database. LncRNA alterations were analyzed in lung cancer patients. Smoking category and packs were evaluated. Correlations between smoking and LncRNA alterations were analyzed. Kaplan-Meier analysis was performed to determine overall survival and disease free survival. RESULTS: There are more non-smokers in LUSC than in LUAD. In both LUAD and LUSC, smoking could increase total mutation counts and fraction of copy number alterations. Smoking index positively correlated with total mutations in LUAD, but not in LUSC. Smoking could trigger lncRNA alterations both in LUAD and LUSC. Smoking regulated different lncRNA between male and female. EXOC3-AS1 and LINC00603 alterations were positively correlated with smoking index in male LUAD smokers. In female LUAD smokers, smoking index was positively correlated with SNHG15, TP53TG1 and LINC01600 and negatively with LINC00609 and PTCSC3. In both male and female LUSC patients, smoking increased or decreased several lncRNA alterations. DGCR5 alteration increased in male LUSC than in female LUSC patients. In female LUSC patients, LOH12CR2 alteration was positively correlated with smoking index. CONCLUSIONS: Smoking promoted LUAD and LUSC development by affecting different lncRNA alterations in different genders.

9.
Clin Invest Med ; 44(2): E48-54, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34152707

RESUMO

PURPOSE: The aim of the study was to describe the use of masks among health care personnel (HCP) exposed to index cases of coronavirus disease 2019 (COVID-19), and to evaluate any association with infection rate. METHODS: We did a retrospective, observational study of HCP at Zhongnan Hospital of Wuhan University for the management of COVID-19 (before person-to-person transmission was official confirmed, no additional protection was provided). A questionnaire was given to all staff listed on the roster in the clinical regions providing care for index patients with COVID-19. All participants were surveyed regarding hand-washing and use of surgical masks and gloves and were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data were analysed (Student's t test and Pearson χ2 test) for an association between infection and use of personal protective equipment. RESULTS: Exposure of a total of 299 non-infected and 30 infected staff was confirmed. None of the 149 staff who reported use of all three preventative measures (hand-washing and use of gloves and masks) became infect-ed. In contrast, all 30 of the staff who became infected had omitted at least one of the measures. Fewer staff who wore surgical masks (P=0.000003) became infected compared with those who did not. Infections rates were significantly lower in HCP from the internal medicine departments, as these personnel generally wore masks. CONCLUSION: An association was found between SARS-CoV-2 infection of HCP and the non-use of masks when working with index cases in clinical settings. We recommend that all HCP follow the strict instructions for prevention and treatment of nosocomial infection during intimate contact with COVID-19, especially staff from surgical departments.


Assuntos
COVID-19/prevenção & controle , Máscaras , Exposição Ocupacional/prevenção & controle , Equipamento de Proteção Individual , Médicos , SARS-CoV-2 , Adulto , COVID-19/transmissão , China , Atenção à Saúde , Feminino , Luvas Cirúrgicas , Desinfecção das Mãos , Pessoal de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
10.
J Clin Lab Anal ; 35(6): e23813, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33969541

RESUMO

BACKGROUND: Although studies have identified hundreds of genetic variants associated with asthma risk, a large fraction of heritability remains unexplained, especially in Chinese individuals. METHODS: To identify genetic risk factors for asthma in a Han Chinese population, 211 asthma-related genes were first selected based on database searches. The genes were then sequenced for subjects in a Discovery Cohort (284 asthma patients and 205 older healthy controls) using targeted next-generation sequencing. Bioinformatics analysis and statistical association analyses were performed to reveal the associations between rare/common variants and asthma, respectively. The identified common risk variants underwent a validation analysis using a Replication Cohort (664 patients and 650 controls). RESULTS: First, we identified 18 potentially functional rare loss-of-function (LOF) variants in 21/284 (7.4%) of the asthma cases. Second, using burden tests, we found that the asthma group had nominally significant (p < 0.05) burdens of rare nonsynonymous variants in 10 genes. Third, 23 common single-nucleotide polymorphisms were associated with the risk of asthma, 7/23 (30.4%) and 9/23 (39.1%) of which were modestly significant (p < 9.1 × 10-4 ) in the Replication Cohort and Combined Cohort, respectively. According to our cumulative risk model involving the modestly associated alleles, middle- and high-risk subjects had a 2.0-fold (95% CI: 1.621-2.423, p = 2.624 × 10-11 ) and 6.0-fold (95% CI: 3.623-10.156, p = 7.086 × 10-12 ) increased risk of asthma, respectively, compared with low-risk subjects. CONCLUSION: This study revealed novel rare and common genetic risk factors for asthma, and provided a cumulative risk model for asthma risk prediction and stratification in Han Chinese individuals.


Assuntos
Asma/genética , Asma/patologia , Biomarcadores/metabolismo , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Asma/epidemiologia , Biomarcadores/análise , Estudos de Casos e Controles , Criança , Pré-Escolar , China/epidemiologia , Estudos de Coortes , Feminino , Seguimentos , Estudo de Associação Genômica Ampla , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
11.
J Clin Lab Anal ; 35(6): e23782, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33942374

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a genetic heterogeneous disease with high mortality and poor prognosis. Hyaluronidase 1 (HYAL1) was found to be upregulated in fibroblasts from IPF patients, and overexpression of HYAL1 could prevent human fetal lung fibroblast proliferation. However, the genetic correlation between the HYAL1 and IPF or connective tissue diseases related interstitial lung disease (CTD-ILD) has not been determined. METHODS: A two-stage study was conducted in Southern Han Chinese population. We sequenced the coding regions and flanking regulatory regions of HYAL1 in stage one (253 IPF cases and 125 controls). A statistically significant variant was further genotyped in stage two (162 IPF cases, 182 CTD-ILD cases, and 225 controls). RESULTS: We identified a nonsynonymous polymorphism (rs117179004, T392M) significantly associated with increased IPF risk (dominant model: OR = 2.239, 95% CI = 1.212-4.137, p = 0.010 in stage one; OR = 2.383, 95% CI = 1.376-4.128, p = 0.002 in stage two). However, we did not observe this association in CTD-ILD (OR = 1.401, 95% CI = 0.790-2.485, p = 0.248). CONCLUSION: Our findings suggest that the nonsynonymous polymorphism (rs117179004, T392M) may confer susceptibility to IPF in Southern Han Chinese, but is not associated with susceptibility to CTD-ILD.


Assuntos
Hialuronoglucosaminidase/genética , Fibrose Pulmonar Idiopática/genética , Polimorfismo de Nucleotídeo Único , Idoso , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Doenças Pulmonares Intersticiais/genética , Masculino , Pessoa de Meia-Idade
13.
Clin Microbiol Infect ; 27(2): 253-257, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33035672

RESUMO

OBJECTIVES: The outbreak of the 2019 coronavirus disease (COVID-19) pandemic in Wuhan, China, has subsided after being hard hit by the disease and subsequent city lockdown. Information on the number of people involved in Wuhan is still inadequate. This study aimed to describe the screening results of 61 437 community members in Wuchang District, Wuhan. METHODS: In mid-May 2020, Wuhan launched a population-scale city-wide SARS-CoV-2 testing campaign, which aimed to perform nucleic acid and viral antibody testing for citizens in Wuhan. Here we show the screening results of cluster sampling of 61 437 residents in Wuchang District, Wuhan, China. RESULTS: A total of 1470 (2.39%, 95% CI 2.27-2.52) individuals were detected positive for at least one antiviral antibody. Among the positive individuals, 324 (0.53%, 95% CI 0.47-0.59) and 1200 (1.95%, 95% CI 1.85-2.07) were positive for immunoglobulin IgM and IgG, respectively, and 54 (0.08%, 95% CI 0.07-0.12) were positive for both antibodies. The positive rate of female carriers of antibodies was higher than those of male counterparts (male-to-female ratio of 0.75), especially in elderly citizens (ratio of 0.18 in 90+ age subgroup), indicating a sexual discrepancy in seroprevalence. In addition, viral nucleic acid detection using real-time PCR had showed 8 (0.013%, 95% CI 0.006-0.026) asymptomatic virus carriers. DISCUSSION: The seroprevalence of SARS-CoV-2 in Wuhan was low. Most Wuhan residents are still susceptible to this virus. Precautions, such as wearing mask, frequent hand hygiene and proper social distance, are necessary before an effective vaccine or antiviral treatments are available.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/epidemiologia , Programas de Rastreamento/estatística & dados numéricos , SARS-CoV-2/imunologia , Distribuição por Idade , Infecções Assintomáticas/epidemiologia , COVID-19/sangue , COVID-19/virologia , Teste para COVID-19 , China/epidemiologia , Cidades/epidemiologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , RNA Viral/genética , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Estudos Soroepidemiológicos
14.
Clin Infect Dis ; 73(11): e4208-e4213, 2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-32173725

RESUMO

BACKGROUND: Since December 2019, coronavirus disease 2019 (COVID-19), caused by severe adult respiratory syndrome coronavirus 2, occurred in Wuhan, and rapidly spread throughout China. This study aimed to clarify the characteristics of patients with refractory COVID-19. METHODS: In this retrospective single-center study, we included 155 consecutive patients with confirmed COVID-19 in Zhongnan Hospital of Wuhan University from 1 January to 5 February. The cases were divided into general and refractory COVID-19 groups according to the clinical efficacy of treatment after hospitalization, and the differences between groups were compared. RESULTS: Compared with patients with general COVID-19 (45.2%), those with refractory disease were older, were more likely to be male, and had more underlying comorbid conditions, a lower incidence of fever, higher maximum temperatures among patients with fever, higher incidences of shortness of breath and anorexia, more severe disease assessment at admission, higher neutrophil, aspartate aminotransferase, lactate dehydrogenase, and C-reactive protein levels, lower platelet counts and albumin levels, and higher incidences of bilateral pneumonia and pleural effusion (P < .05). Patients with refractory COVID-19 were more likely to receive oxygen, mechanical ventilation, expectorant, and adjunctive treatment, including corticosteroids, antiviral drugs, and immune enhancers (P < .05). Considering the factors of disease severity at admission, mechanical ventilation, and intensive care unit transfer, patients with refractory COVID-19 were also more likely to be male, have manifestations of anorexia on admission, and receive oxygen, expectorant, and adjunctive agents (P < .05). CONCLUSION: In nearly 50% of patients with COVID-19 obvious clinical and radiological remission was not achieved within 10 days after hospitalization. Male, anorexia, and no fever at admission was predictive of poor treatment efficacy.


Assuntos
COVID-19 , Adulto , China/epidemiologia , Feminino , Febre , Hospitalização , Humanos , Masculino , Estudos Retrospectivos , SARS-CoV-2
15.
AJR Am J Roentgenol ; 217(1): 83-92, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-32903056

RESUMO

BACKGROUND. Chest CT findings have the potential to guide treatment of hospitalized patients with coronavirus disease (COVID-19). OBJECTIVE. The purpose of this study was to assess a CT visual severity score in hospitalized patients with COVID-19, with attention to temporal changes in the score and the role of the score in a model for predicting in-hospital complications. METHODS. This retrospective study included 161 inpatients with COVID-19 from three hospitals in China who underwent serial chest CT scans during hospitalization. CT examinations were evaluated using a visual severity scoring system. The temporal pattern of the CT visual severity score across serial CT examinations during hospitalization was characterized using a generalized spline regression model. A prognostic model to predict major complications, including in-hospital mortality, was created using the CT visual severity score and clinical variables. External model validation was evaluated by two independent radiologists in a cohort of 135 patients from a different hospital. RESULTS. The cohort included 91 survivors with nonsevere disease, 55 survivors with severe disease, and 15 patients who died during hospitalization. Median CT visual lung severity score in the first week of hospitalization was 2.0 in survivors with non-severe disease, 4.0 in survivors with severe disease, and 11.0 in nonsurvivors. CT visual severity score peaked approximately 9 and 12 days after symptom onset in survivors with nonsevere and severe disease, respectively, and progressively decreased in subsequent hospitalization weeks in both groups. In the prognostic model, in-hospital complications were independently associated with a severe CT score (odds ratio [OR], 31.28), moderate CT score (OR, 5.86), age (OR, 1.09 per 1-year increase), and lymphocyte count (OR, 0.03 per 1 × 109/L increase). In the validation cohort, the two readers achieved C-index values of 0.92-0.95, accuracy of 85.2-86.7%, sensitivity of 70.7-75.6%, and specificity of 91.4-91.5% for predicting in-hospital complications. CONCLUSION. A CT visual severity score is associated with clinical disease severity and evolves in a characteristic fashion during hospitalization for COVID-19. A prognostic model based on the CT visual severity score and clinical variables shows strong performance in predicting in-hospital complications. CLINICAL IMPACT. The prognostic model using the CT visual severity score may help identify patients at highest risk of poor outcomes and guide early intervention.


Assuntos
COVID-19/diagnóstico , Pacientes Internados , Pulmão/diagnóstico por imagem , Radiografia Torácica/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , China , Estudos de Coortes , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença , Sobreviventes , Tempo
16.
Fundam Clin Pharmacol ; 35(5): 822-831, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33336420

RESUMO

The poor outcomes in advanced non-small-cell lung cancer (NSCLC) necessitate new treatments. Recent studies emphasize anisomycin as a promising anti-cancer drug candidate. In this work, we systematically investigated the efficacy of anisomycin alone and its combination with the standard-of-care drugs in NSCLC. We showed that anisomycin inhibited growth, migration, and survival in NSCLC cells regardless of genetic mutation status, and to a greater extent than in normal lung epithelial cells. Isobologram analysis showed that the combination of anisomycin with cisplatin, paclitaxel, or gefitinib was synergistic in NSCLC but not normal lung cells. We further demonstrated that anisomycin inhibited NSCLC growth in mice. The combination of anisomycin with cisplatin was more effective than cisplatin alone and completely arrested NSCLC growth throughout the whole duration of treatment. JNK and p38 MAPK were not required for anisomycin's action. In contrast, anisomycin inhibits PI3K/Akt/mTOR pathway. Overexpression of constitutively active Akt reversed the pro-apoptotic effect of anisomycin. Our work demonstrates the selective anti-NSCLC activity of anisomycin via suppressing PI3K/Akt/mTOR. Our findings provide preclinical evidence to initialize the clinical trial of using anisomycin to sensitize NSCLC to current therapy.


Assuntos
Anisomicina/farmacologia , Antineoplásicos/farmacocinética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Inibidores da Síntese de Proteínas/farmacologia , Animais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Receptores ErbB/antagonistas & inibidores , Humanos , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo
17.
Curr Med Res Opin ; 37(2): 219-224, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33136449

RESUMO

PURPOSE: To describe the radiological features of coronavirus disease 19 (COVID-19) and to explore the significant signs that indicate severity of disease. MATERIALS AND METHODS: We collected data retrospectively of 180 cases of COVID-19, from 15 January 2020 to 31 March 2020, from both the Wuhan Zhongnan and Beijing Ditan Hospitals, including 103 cases of mild and 77 cases of severe pneumonia. All patients had their first chest computed tomography scan within five days of symptom onset. The dandelion sign was defined by a focal ground glass opacity (GGO) with a central thickening of the airway wall, and the focal crazy paving sign was defined by a focal GGO with thickening of the interlobular septa. RESULTS: Consolidation presented in only 4.9% (5/103) of the mild pneumonia cases, which was significantly lower than that in severe pneumonia cases (70.1% 54/77), p < .001). Multifocal distribution and pure GGOs were observed more frequently in severe cases of pneumonia (p < .05). The dandelion sign was present in 86.4% (89/103) of the mild pneumonia cases, significantly more frequent than those with severe pneumonia (13.0% [10/77], p < .001). The focal crazy paving sign presented in 65.0% (67/103) of the mild pneumonia cases and was significantly more frequent than in severe cases (23.4% [18/77], p < .001). The hospital stay duration of the mild pneumonia group (13.6 ± 7.2 days) was significantly shorter than the severe pneumonia group (26.6 ± 11.7 days, p < .001). CONCLUSIONS: Consolidation, pure GGO and multifocal distribution on a CT scan were associated with severe COVID-19. The dandelion and focal crazy paving signs indicate mild COVID-19.


Assuntos
COVID-19/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Adulto , Idoso , COVID-19/fisiopatologia , Coronavirus , Infecções por Coronavirus , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pneumonia , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X/métodos
18.
Front Pharmacol ; 12: 788714, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35002722

RESUMO

Despite past extensive studies, the mechanisms underlying pulmonary fibrosis (PF) still remain poorly understood. The aberrantly activated lung myofibroblasts, predominantly emerging through fibroblast-to-myofibroblast differentiation, are considered to be the key cells in PF, resulting in excessive accumulation of extracellular matrix (ECM). Latent transforming growth factor-ß (TGFß) binding protein-2 (LTBP2) has been suggested as playing a critical role in modulating the structural integrity of the ECM. However, its function in PF remains unclear. Here, we demonstrated that lungs originating from different types of patients with PF, including idiopathic PF and rheumatoid arthritis-associated interstitial lung disease, and from mice following bleomycin (BLM)-induced PF were characterized by increased LTBP2 expression in activated lung fibroblasts/myofibroblasts. Moreover, serum LTBP2 was also elevated in patients with COVID-19-related PF. LTBP2 silencing by lentiviral shRNA transfection protected against BLM-induced PF and suppressed fibroblast-to-myofibroblast differentiation in vivo and in vitro. More importantly, LTBP2 overexpression was able to induce differentiation of lung fibroblasts to myofibroblasts in vitro, even in the absence of TGFß1. By further mechanistic analysis, we demonstrated that LTBP2 silencing prevented fibroblast-to-myofibroblast differentiation and subsequent PF by suppressing the phosphorylation and nuclear translocation of NF-κB signaling. LTBP2 overexpression-induced fibroblast-to-myofibroblast differentiation depended on the activation of NF-κB signaling in vitro. Therefore, our data indicate that intervention to silence LTBP2 may represent a promising therapy for PF.

19.
Respir Res ; 21(1): 327, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33302921

RESUMO

Since the coronavirus disease 2019 (COVID-19) identified in Wuhan, Hubei, China in December 2019, it has been characterized as a pandemic by World Health Organization (WHO). It was reported that asymptomatic persons are potential sources of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We present an outbreak among health-care workers incited by a doctor who cared a patient with COVID-19 in a Hospital in Wuhan, Hubei, China, which indicates existence of super-spreader even during incubation period.


Assuntos
COVID-19/transmissão , Portador Sadio , Período de Incubação de Doenças Infecciosas , Transmissão de Doença Infecciosa do Paciente para o Profissional , Exposição por Inalação/efeitos adversos , Exposição Ocupacional/efeitos adversos , SARS-CoV-2/patogenicidade , Idoso , COVID-19/diagnóstico , COVID-19/virologia , China , Feminino , Humanos , Fatores de Tempo , Virulência
20.
JMIR Public Health Surveill ; 6(4): e25174, 2020 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-33315585

RESUMO

BACKGROUND: Different states in the United States had different nonpharmaceutical public health interventions during the COVID-19 pandemic. The effects of those interventions on hospital use have not been systematically evaluated. The investigation could provide data-driven evidence to potentially improve the implementation of public health interventions in the future. OBJECTIVE: We aim to study two representative areas in the United States and one area in China (New York State, Ohio State, and Hubei Province), and investigate the effects of their public health interventions by time periods according to key interventions. METHODS: This observational study evaluated the numbers of infected, hospitalized, and death cases in New York and Ohio from March 16 through September 14, 2020, and Hubei from January 26 to March 31, 2020. We developed novel Bayesian generalized compartmental models. The clinical stages of COVID-19 were stratified in the models, and the effects of public health interventions were modeled through piecewise exponential functions. Time-dependent transmission rates and effective reproduction numbers were estimated. The associations of interventions and the numbers of required hospital and intensive care unit beds were studied. RESULTS: The interventions of social distancing, home confinement, and wearing masks significantly decreased (in a Bayesian sense) the case incidence and reduced the demand for beds in all areas. Ohio's transmission rates declined before the state's "stay at home" order, which provided evidence that early intervention is important. Wearing masks was significantly associated with reducing the transmission rates after reopening, when comparing New York and Ohio. The centralized quarantine intervention in Hubei played a significant role in further preventing and controlling the disease in that area. The estimated rates that cured patients become susceptible in all areas were small (<0.0001), which indicates that they have little chance to get the infection again. CONCLUSIONS: The series of public health interventions in three areas were temporally associated with the burden of COVID-19-attributed hospital use. Social distancing and the use of face masks should continue to prevent the next peak of the pandemic.


Assuntos
COVID-19/prevenção & controle , COVID-19/terapia , Hospitalização/estatística & dados numéricos , Prática de Saúde Pública/estatística & dados numéricos , Teorema de Bayes , COVID-19/epidemiologia , China/epidemiologia , Humanos , Máscaras/estatística & dados numéricos , Modelos Estatísticos , Distanciamento Físico , Quarentena/estatística & dados numéricos , Estados Unidos/epidemiologia
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