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1.
Ann Intensive Care ; 10(1): 99, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737627

RESUMO

BACKGROUND: Since December 2019, an outbreak of Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) initially emerged in Wuhan, China, and has spread worldwide now. Clinical features of patients with COVID-19 have been described. However, risk factors leading to in-hospital deterioration and poor prognosis in COVID-19 patients with severe disease have not been well identified. METHODS: In this retrospective, single-center cohort study, 1190 adult inpatients (≥ 18 years old) with laboratory-confirmed COVID-19 and determined outcomes (discharged or died) were included from Wuhan Infectious Disease Hospital from December 29, 2019 to February 28, 2020. The final follow-up date was March 2, 2020. Clinical data including characteristics, laboratory and imaging information as well as treatments were extracted from electronic medical records and compared. A multivariable logistic regression model was used to explore the potential predictors associated with in-hospital deterioration and death. RESULTS: 1190 patients with confirmed COVID-19 were included. Their median age was 57 years (interquartile range 47-67 years). Two hundred and sixty-one patients (22%) developed a severe illness after admission. Multivariable logistic regression demonstrated that higher SOFA score (OR 1.32, 95% CI 1.22-1.43, per score increase, p < 0.001 for deterioration and OR 1.30, 95% CI 1.11-1.53, per score increase, p = 0.001 for death), lymphocytopenia (OR 1.81, 95% CI 1.13-2.89 p = 0.013 for deterioration; OR 4.44, 95% CI 1.26-15.87, p = 0.021 for death) on admission were independent risk factors for in-hospital deterioration from not severe to severe disease and for death in severe patients. On admission D-dimer greater than 1 µg/L (OR 3.28, 95% CI 1.19-9.04, p = 0.021), leukocytopenia (OR 5.10, 95% CI 1.25-20.78), thrombocytopenia (OR 8.37, 95% CI 2.04-34.44) and history of diabetes (OR 11.16, 95% CI 1.87-66.57, p = 0.008) were also associated with higher risks of in-hospital death in severe COVID-19 patients. Shorter time interval from illness onset to non-invasive mechanical ventilation in the survivors with severe disease was observed compared with non-survivors (10.5 days, IQR 9.25-11.0 vs. 16.0 days, IQR 11.0-19.0 days, p = 0.030). Treatment with glucocorticoids increased the risk of progression from not severe to severe disease (OR 3.79, 95% CI 2.39-6.01, p < 0.001). Administration of antiviral drugs especially oseltamivir or ganciclovir is associated with a decreased risk of death in severe patients (OR 0.17, 95% CI 0.05-0.64, p < 0.001). CONCLUSIONS: High SOFA score and lymphocytopenia on admission could predict that not severe patients would develop severe disease in-hospital. On admission elevated D-dimer, leukocytopenia, thrombocytopenia and diabetes were independent risk factors of in-hospital death in severe patients with COVID-19. Administration of oseltamivir or ganciclovir might be beneficial for reducing mortality in severe patients.

2.
Front Immunol ; 11: 1104, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636835

RESUMO

Background: High-mobility group box 1 protein (HMGB1) was identified as a highly conserved DNA binding nuclear protein, which participates in the processes of acute lung injury (ALI). HMGB1 binds to its specific receptors not only to activate the nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) pathways but also to regulate the activation of the phosphatidylinositol 3'-kinase/protein kinase B/mammalian target of the rapamycin (PI3K/AKT/mTOR) pathway. Mature dendritic cells (DCs) regulate acute lung inflammation and pathological injury in ALI. In addition, studies have shown that the activation of the PI3K/AKT/mTOR signaling pathway may regulate the function and maturation of DCs. Objective: Therefore, we speculate that HMGB1/PI3K/Akt/mTOR signaling participates in regulating the pathological process of ALI by regulating the maturation and function of DCs. Methods: Anti-HMGB1 antibody, rHMGB1, or LY294002 (PI3K inhibitor) was administered in a murine model of lipopolysaccharide (LPS)-induced ALI. For in vitro studies, generated bone marrow-derived dendritic cells (BMDCs) primed by LPS were stimulated with the same reagents. The effects of these different treatments were observed on the expression of PI3K, AKT, and mTOR and on the function of DCs. Results: HMGB1 upregulated the expression of PI3K, Akt, and mTOR mRNA and phosphorylated proteins in BMDCs. The HMGB1/PI3K/Akt/mTOR signaling pathway induced the maturation and antigen-presenting ability of lung DCs, mediated the percentage of myeloid DCs (mDCs), and enhanced the adhesion and chemotactic ability of lung DCs. Conclusions: HMGB1/PI3K/Akt/mTOR signaling participates in the pathological process of ALI by regulating the maturation and functions of DCs.

3.
Crit Care ; 24(1): 394, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631393

RESUMO

BACKGROUND: The global numbers of confirmed cases and deceased critically ill patients with COVID-19 are increasing. However, the clinical course, and the 60-day mortality and its predictors in critically ill patients have not been fully elucidated. The aim of this study is to identify the clinical course, and 60-day mortality and its predictors in critically ill patients with COVID-19. METHODS: Critically ill adult patients admitted to intensive care units (ICUs) from 3 hospitals in Wuhan, China, were included. Data on demographic information, preexisting comorbidities, laboratory findings at ICU admission, treatments, clinical outcomes, and results of SARS-CoV-2 RNA tests and of serum SARS-CoV-2 IgM were collected including the duration between symptom onset and negative conversion of SARS-CoV-2 RNA. RESULTS: Of 1748 patients with COVID-19, 239 (13.7%) critically ill patients were included. Complications included acute respiratory distress syndrome (ARDS) in 164 (68.6%) patients, coagulopathy in 150 (62.7%) patients, acute cardiac injury in 103 (43.1%) patients, and acute kidney injury (AKI) in 119 (49.8%) patients, which occurred 15.5 days, 17 days, 18.5 days, and 19 days after the symptom onset, respectively. The median duration of the negative conversion of SARS-CoV-2 RNA was 30 (range 6-81) days in 49 critically ill survivors that were identified. A total of 147 (61.5%) patients deceased by 60 days after ICU admission. The median duration between ICU admission and decease was 12 (range 3-36). Cox proportional-hazards regression analysis revealed that age older than 65 years, thrombocytopenia at ICU admission, ARDS, and AKI independently predicted the 60-day mortality. CONCLUSIONS: Severe complications are common and the 60-day mortality of critically ill patients with COVID-19 is considerably high. The duration of the negative conversion of SARS-CoV-2 RNA and its association with the severity of critically ill patients with COVID-19 should be seriously considered and further studied.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Idoso , China/epidemiologia , Infecções por Coronavirus/terapia , Estado Terminal , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/terapia , Estudos Retrospectivos , Fatores de Risco
4.
Virol Sin ; 2020 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-32720214

RESUMO

The coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has spread around the world with high mortality. To diagnose promptly and accurately is the vital step to effectively control its pandemic. Dynamic characteristics of SARS-CoV-2-specific antibodies which are important for diagnosis of infection have not been fully demonstrated. In this retrospective, single-center, observational study, we enrolled the initial 131 confirmed cases of COVID-19 at Jin-Yin-Tan Hospital who had at least one-time antibody tested during their hospitalization. The dynamic changes of IgM and IgG antibodies to SARS-CoV-2 nucleocapsid protein in 226 serum samples were detected by ELISA. The sensitivities of IgM and IgG ELISA detection were analyzed. Result showed that the sensitivity of the IgG ELISA detection (92.5%) was significantly higher than that of the IgM (70.8%) (P < 0.001). The meantimes of seroconversion for IgM and IgG were 6 days and 3 days, respectively. The IgM and IgG antibody levels peaked at around 18 days and 23 days, and then IgM fell to below the baseline level at about day 36, whereas IgG maintained at a relatively high level. In conclusion, antibodies should be detected to aid in diagnosis of COVID-19 infection. IgG could be a sensitive indicator for retrospective diagnosis and contact tracing, while IgM could be an indicator of early infection.

5.
Toxicology ; 442: 152537, 2020 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-32663520

RESUMO

Long-term exposure to isoflurane may induce long-term developmental neurotoxicity and cognitive impairments in the neonatal brains. Trilobatin, a leaf extract from the Chinese traditional sweet tea Lithocarpus polystachyus Rehd, possesses various biological properties including anti-inflammatory and anti-oxidant properties. Our study aimed to explore the neuroprotective effect of trilobatin on isoflurane-induced neurotoxicity in mouse hippocampal neuronal HT22 cells. The effects of trilobatin on cell viability, LDH release, apoptosis, and caspase-3/7 activity in isoflurane-induced HT22 cells were explored by CCK-8, LDH release assay, flow cytometry analysis, and caspase-3/7 activity assay, respectively. Oxidative stress was evaluated by measuring the levels of reactive oxygen species (ROS) and malonyldialdehyde (MDA) and activities of superoxide dismutase (SOD) and catalase (CAT). The expression of nuclear erythroid-2 related factor 2 (Nrf2), nuclear Nrf2, heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO1) was determined by western blot and qRT-PCR. Results suggested that exposure to isoflurane significantly reduced cell viability and increased LDH release, apoptotic rate and caspase-3/7 activity in HT22 cells, which were abolished by trilobatin. Trilobatin reversed isoflurane-induced increase of ROS and MDA levels and reduction of SOD and CAT activities in HT22 cells. Additionally, trilobatin promoted the nuclear translocation of Nrf2 as well as the mRNA and protein expression of HO-1 and NQO1 in HT22 cells exposed to isoflurane. Nrf2 knockdown attenuated the effects of trilobatin on isoflurane-induced viability reduction, LDH release, apoptosis, and oxidative stress in HT22 cells. Overall, trilobatin protected HT22 cells against isoflurane-induced neurotoxicity via activating the Nrf2/antioxidant response element (ARE) pathway.

7.
Brain Behav Immun ; 88: 50-58, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32512133

RESUMO

Sleep is known to play an important role in immune function. However, the effects of sleep quality during hospitalization for COVID-19 remain unclear. This retrospective, single-center cohort study was conducted to investigate the effects of sleep quality on recovery from lymphopenia and clinical outcomes in hospitalized patients with laboratory-confirmed COVID-19 admitted to the West District of Wuhan Union Hospital between January 25 and March 15, 2020. The Richards-Campbell sleep questionnaire (RCSQ) and Pittsburgh Sleep Quality Index (PSQI) were used to assess sleep quality. The epidemiological, demographic, clinical, laboratory, treatment, and outcome data were collected from electronic medical records and compared between the good-sleep group and poor-sleep group. In all, 135 patients (60 in good-sleep group and 75 in poor-sleep group) were included in this study. There were no significant between-group differences regarding demographic and baseline characteristics, as well as laboratory parameters upon admission and in-hospital treatment. Compared with patients in the good-sleep group, patients in the poor-sleep group had lower absolute lymphocyte count (ALC) (day 14: median, 1.10 vs 1.32, P = 0.0055; day 21: median, 1.18 vs 1.48, P = 0.0034) and its reduced recovery rate (day 14: median, 56.91 vs 69.40, P = 0.0255; day 21: median, 61.40 vs 111.47, P = 0.0003), as well as increased neutrophil-to-lymphocyte ratio (NLR; day 14: median, 3.17 vs 2.44, P = 0.0284; day 21: median, 2.73 vs 2.23, P = 0.0092) and its associated deterioration rate (day 14: median, -39.65 vs -61.09, P = 0.0155; day 21: median, -51.40% vs -75.43, P = 0.0003). Nine [12.0%] patients in the poor-sleep group required ICU care (P = 0.0151); meanwhile, none of the patients in good-sleep group required ICU care. Patients in the poor-sleep group had increased duration of hospital stay (33.0 [23.0-47.0] days vs 25.0 [20.5-36.5] days, P = 0.0116) compared to those in the good-sleep group. An increased incidence of hospital-acquired infection (seven [9.3%] vs one [1.7%]) was observed in the poor-sleep group compared to the good-sleep group; however, this difference was not significant (P = 0.1316). In conclusion, poor sleep quality during hospitalization in COVID-19 patients with lymphopenia is associated with a slow recovery from lymphopenia and an increased need for ICU care.

8.
Lancet Respir Med ; 8(7): 717-725, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32422180

RESUMO

Global health care is experiencing an unprecedented surge in the number of critically ill patients who require mechanical ventilation due to the COVID-19 pandemic. The requirement for relatively long periods of ventilation in those who survive means that many are considered for tracheostomy to free patients from ventilatory support and maximise scarce resources. COVID-19 provides unique challenges for tracheostomy care: health-care workers need to safely undertake tracheostomy procedures and manage patients afterwards, minimising risks of nosocomial transmission and compromises in the quality of care. Conflicting recommendations exist about case selection, the timing and performance of tracheostomy, and the subsequent management of patients. In response, we convened an international working group of individuals with relevant expertise in tracheostomy. We did a literature and internet search for reports of research pertaining to tracheostomy during the COVID-19 pandemic, supplemented by sources comprising statements and guidance on tracheostomy care. By synthesising early experiences from countries that have managed a surge in patient numbers, emerging virological data, and international, multidisciplinary expert opinion, we aim to provide consensus guidelines and recommendations on the conduct and management of tracheostomy during the COVID-19 pandemic.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Internacionalidade , Pneumonia Viral/terapia , Guias de Prática Clínica como Assunto , Traqueostomia/métodos , Infecções por Coronavirus/prevenção & controle , Cuidados Críticos/métodos , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle
10.
J Cardiothorac Vasc Anesth ; 34(7): 1727-1732, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32418832

RESUMO

The COVID-19 pandemic is spreading globally. COVID-19 has an effect on the systemic state, cardiopulmonary function and primary disease of patients undergoing surgery. COVID-19's high contagiousness makes anesthesia and intraoperative management more difficult. This expert consensus aims to comprehensively introduce the application of perioperative ultrasound in COVID-19 patients, including pulmonary ultrasound and anesthesia management, ultrasound and airway management, ultrasound-guided regional anesthesia and echocardiography for COVID-19 patients.


Assuntos
Anestesia/métodos , Betacoronavirus , Infecções por Coronavirus/diagnóstico por imagem , Assistência Perioperatória/métodos , Pneumonia Viral/diagnóstico por imagem , Ultrassonografia/métodos , Manuseio das Vias Aéreas/métodos , Anestesia por Condução/métodos , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/diagnóstico por imagem , Infecções por Coronavirus/complicações , Infecções por Coronavirus/transmissão , Ecocardiografia/métodos , Hemodinâmica , Humanos , Pulmão/diagnóstico por imagem , Pneumopatias/diagnóstico por imagem , Pneumopatias/microbiologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/transmissão , Traqueotomia/métodos , Ultrassonografia de Intervenção/métodos , Desmame do Respirador/métodos
11.
Crit Care ; 24(1): 219, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32410714

RESUMO

BACKGROUND: A COVID-19 outbreak started in Wuhan, China, last December and now has become a global pandemic. The clinical information in caring of critically ill patients with COVID-19 needs to be shared timely, especially under the situations that there is still a largely ongoing spread of COVID-19 in many countries. METHODS: A multicenter prospective observational study investigated all the COVID-19 patients received in 19 ICUs of 16 hospitals in Wuhan, China, over 24 h between 8 AM February 2h and 8 AM February 27, 2020. The demographic information, clinical characteristics, vital signs, complications, laboratory values, and clinical managements of the patients were studied. RESULTS: A total of 226 patients were included. Their median (interquartile range, IQR) age was 64 (57-70) years, and 139 (61.5%) patients were male. The duration from the date of ICU admission to the study date was 11 (5-17) days, and the duration from onset of symptoms to the study date was 31 (24-36) days. Among all the patients, 155 (68.6%) had at least one coexisting disease, and their sequential organ failure assessment score was 4 (2-8). Organ function damages were found in most of the patients: ARDS in 161 (71.2%) patients, septic shock in 34 (15.0%) patients, acute kidney injury occurred in 57 (25.2%) patients, cardiac injury in 61 (27.0%) patients, and lymphocytopenia in 160 (70.8%) patients. Of all the studied patients, 85 (37.6%) received invasive mechanical ventilation, including 14 (6.2%) treated with extracorporeal membrane oxygenation (ECMO) at the same time, 20 (8.8%) received noninvasive mechanical ventilation, and 24 (10.6%) received continuous renal replacement therapy. By April 9, 2020, 87 (38.5%) patients were deceased and 15 (6.7%) were still in the hospital. CONCLUSIONS: Critically ill patients with COVID-19 are associated with a higher risk of severe complications and need to receive an intensive level of treatments. COVID-19 poses a great strain on critical care resources in hospitals. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000030164. Registered on February 24, 2020, http://www.chictr.org.cn/edit.aspx?pid=49983&htm=4.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Cuidados Críticos , Surtos de Doenças , Unidades de Terapia Intensiva , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Idoso , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Prospectivos , Resultado do Tratamento
12.
J Thromb Haemost ; 18(6): 1469-1472, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32302435

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes novel coronavirus disease 2019 (COVID-19), is spreading rapidly around the world. Thrombocytopenia in patients with COVID-19 has not been fully studied. OBJECTIVE: To describe thrombocytopenia in patients with COVID-19. METHODS: For each of 1476 consecutive patients with COVID-19 from Jinyintan Hospital, Wuhan, China, nadir platelet count during hospitalization was retrospectively collected and categorized into (0, 50], (50, 100], (100-150], or (150-) groups after taking the unit (×109 /L) away from the report of nadir platelet count. Nadir platelet counts and in-hospital mortality were analyzed. RESULTS: Among all patients, 238 (16.1%) patients were deceased and 306 (20.7%) had thrombocytopenia. Compared with survivors, non-survivors were older, were more likely to have thrombocytopenia, and had lower nadir platelet counts. The in-hospital mortality was 92.1%, 61.2%, 17.5%, and 4.7% for (0, 50], (50, 100], (100-150], and (150-) groups, respectively. With (150-) as the reference, nadir platelet counts of (100-150], (50, 100], and (0, 50] groups had a relative risk of 3.42 (95% confidence interval [CI] 2.36-4.96), 9.99 (95% CI 7.16-13.94), and 13.68 (95% CI 9.89-18.92), respectively. CONCLUSIONS: Thrombocytopenia is common in patients with COVID-19, and it is associated with increased risk of in-hospital mortality. The lower the platelet count, the higher the mortality becomes.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/mortalidade , Mortalidade Hospitalar , Pneumonia Viral/mortalidade , Trombocitopenia/mortalidade , Idoso , China , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Contagem de Plaquetas , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Trombocitopenia/sangue , Trombocitopenia/diagnóstico , Trombocitopenia/virologia
13.
Neuroscience ; 431: 222-236, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32081723

RESUMO

Chronic sleep-restriction (SR) is shown to be correlated with neurodevelopmental disorders. However, the effects of SR during stroke recovery on neurorepair remain unclear. In this study, mice were subjected to 60 min of cerebral ischemia followed by reperfusion. The SR protocol was accomplished by depriving mice of sleep for 20 h/day for 14 days starting at 14 days post-ischemia. We found that SR increased CD169+ macrophages infiltration into the ischemic brain parenchyma and inhibited neurogenesis and functional recovery. SR decreased CD169+ macrophages infiltration into the choroid plexus (CP) and cerebrospinal fluid (CSF), accompanied by increased expression of Chemokine C-X3-C-Motif Ligand 1 (CX3CL1) and intercellular adhesion molecule (ICAM-1) via IFN-γ/IFN-γR signaling in the CP. When splenic CD169+ macrophages sorted from Kaede transgenic mice were administered into CSF of C57BL/6 mice, they homed to the ischemic brain parenchyma. Moreover, blockade of IFN-γ/IFN-γR signaling, CX3CL1 or ICAM-1 decreased CD169+ macrophages infiltration into the CP, CSF and ischemic brain parenchyma, as well as decreasing neurogenesis and functional recovery after SR. The promoting roles of infiltrated CD169+ macrophages in post-stroke neurogenesis were due to increasing regulatory T cells (Tregs) in the ischemic brain parenchyma. Furthermore, dexmedetomidine treatment during SR increased CD169+ macrophages infiltration into the CP, CSF and ischemic brain parenchyma, and promoted neurogenesis and functional recovery. Taken together, our results showed that SR during stroke recovery decreased Tregs in the ischemic brain parenchyma by decreasing CD169+ macrophages infiltration to the ischemic brain parenchyma across the CP, which inhibited neurogenesis and functional recovery.

14.
Life Sci ; 246: 117415, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32035932

RESUMO

High-mobility group box 1 protein (HMGB1) is a crucial proinflammatory cytokine that contributes to acute lung injury (ALI). Macrophages are known to express the primary receptors (Toll-like receptor [TLR] 2, and TLR4) of HMGB1 for transmitting intracellular signals. Studies have revealed that double-stranded RNA activated protein kinase R (PKR), which is expressed in macrophages, participates in ALI by regulating macrophage polarization and proinflammatory cytokine release, and that PKR is normally activated by a subset of TLRs. The present study investigated whether HMGB1 engages in ALI by activating PKR in macrophages and inducing classically activated macrophage (M1) polarization via TLR2- and TLR4-mediated nuclear factor (NF)-κB signaling pathways. In an vivo mouse model of lipopolysaccharide (LPS)-induced ALI, anti-HMGB1, rHMGB1, LPS-RS (TLR2 and TLR4 antagonist), or C16 (PKR inhibitor) was administered to mice 2 h after LPS challenge or 1 h before LPS challenge. In vitro, bone marrow-derived macrophages from mice primed with LPS were stimulated with or without anti-HMGB1, rHMGB1, LPS-RS, or C16. Our studies revealed that rHMGB1 stimulation induced M1 polarization in ALI, and that anti-HMGB1 and C16 treatments had the opposite effect. Anti-HMGB1 and LPS-RS significantly inhibited LPS-induced PKR expression in macrophages; however, rHMGB1 administration increased PKR expression. These results indicate that HMGB1 participates in the pathogenesis of ALI by activating PKR in macrophages and inducing M1 polarization through TLR2- and TLR4-mediated NF-κB signaling pathways.


Assuntos
Lesão Pulmonar Aguda/metabolismo , Proteína HMGB1/fisiologia , Ativação de Macrófagos , eIF-2 Quinase/metabolismo , Lesão Pulmonar Aguda/etiologia , Animais , Western Blotting , Modelos Animais de Doenças , Ativação Enzimática , Ensaio de Imunoadsorção Enzimática , Proteína HMGB1/metabolismo , Interleucinas/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , Proteínas da Matriz Viral
15.
Lancet Respir Med ; 8(5): 475-481, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32105632

RESUMO

BACKGROUND: An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia. METHODS: In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation. FINDINGS: Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3-11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients. INTERPRETATION: The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1-2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced. FUNDING: None.


Assuntos
Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/isolamento & purificação , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Estado Terminal , Feminino , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Respiração Artificial/estatística & dados numéricos , Síndrome do Desconforto Respiratório do Adulto/mortalidade , Síndrome do Desconforto Respiratório do Adulto/terapia , Síndrome do Desconforto Respiratório do Adulto/virologia , Estudos Retrospectivos , Resultado do Tratamento
16.
Int Immunopharmacol ; 81: 106257, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32044659

RESUMO

The activation of NLRP3 inflammasome and NF-κB pathway, associating with oxidativestress, have been implicated in the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). NecroX-5 has been reported to exhibit theeffectsofanti-oxidation and anti-stress in various diseases. However, the role of NecroX-5 in ALI has not been explicitly demonstrated. The aim of this study was to explore the therapeutic effects and potential mechanism action of NecroX-5 on ALI. Here, we found that NecroX-5 pretreatment dramatically diminished the levels of IL-1ß, IL-18 and ROS in in RAW264.7 cells challenged with LPS and ATP. Furthermore, NecroX-5 suppressed the activation of NLRP3 inflammasome and NF-κB signalpathway. In addition, NecroX-5 also inhibited the thioredoxin-interacting protein (TXNIP) expression. In vivo, NecroX-5 reduced the LPS-induced lung histopathological injury, the number of TUNEL-positive cells, lung wet/dry (W/D) ratio, levels of total protein and inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) in mice. Additionally, LPS-induced upregulation of myeloperoxidase (MPO), ROS production and malondialdehyde (MDA) were inhibited by NecroX-5 administration. Thus, our results demonstrate that NecroX-5 protects against LPS-induced ALI by inhibiting TXNIP/NLRP3 and NF-κB.

18.
Angew Chem Int Ed Engl ; 59(2): 689-694, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31617286

RESUMO

Quaternary ammonium salts were synthesized in moderate to good yields through double oxidative C-H bond activation on azobenzenes. The mechanism of the highly regioselective reaction of 2-azobiaryls with alkenes to give orange-red-fluorescent cinnolino[2,3-f]phenanthridin-9-ium salts and 15H-cinnolino[2,3-f]phenanthridin-9-ium-10-ide is proposed to involve ortho C-H olefination of the 2-azobiaryl compound with the alkene, intramolecular aza-Michael addition, concerted metalation-deprotonation (CMD), reductive elimination, and oxidation.

19.
Exp Cell Res ; 386(1): 111708, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31682811

RESUMO

Recent studies revealed that macrophages are polarized towards the M2 phenotype in an ovalbumin (OVA)-induced asthmatic model. Alveolar macrophages (AMs) are immune barriers in alveoli to various pathogens in the respiratory tract; AMs suppress Th2 cell proliferation, inhibit interleukin (IL)-4, IL-5, and IL-13 secretion, and protect against airway hyperresponsiveness in allergic asthma. However, the polarization status and effects of different types of AMs in the pathogenesis of asthma are not known. ATP/P2X7r, expressed mainly on macrophages and dendritic cells, is associated with acute and chronic asthmatic airway inflammation and Th2 immune responses in mice and humans and functions by activating the NLRP3 inflammasome complex and inducing proinflammatory cytokine release (IL-1ß and IL-18). Therefore, we evaluated the association between the ATP/P2X7r axis and different types of AMs in the pathology of allergic asthma. A murine AM-depleted asthma model was established by administration of clodronate-encapsulated liposomes, and M1-or M2-AMs were adoptively transferred to confirm the effects of different AMs in allergic asthma. Brilliant Blue G and BzATP were administered to OVA/HDM-induced mice in vivo. Lipopolysaccharide + OVA, ATP, Brilliant Blue G, and BzATP were used to stimulate AMs isolated from control and asthmatic mice. We found that selective depletion of AMs aggravated lung inflammation in asthmatic mice. Further, M2-type AMs may play a key role in mediating asthmatic inflammatory responses via the adoptive transfer of M2-type AMs to AM-depleted asthmatic mice, and the phenotype of AMs differentiated to M2 type in asthma. P2X7r expression in M2-type AMs was higher than that in M1-type AMs. Activating P2X7r induced polarization of M2-type AMs and inhibited polarization of M1-type AMs, while blockage of P2X7r had the opposite effect. The ATP/P2X7r axis may participate in the pathogenesis of asthma by mediating the M2-type AM polarization.


Assuntos
Trifosfato de Adenosina/metabolismo , Asma/imunologia , Ativação de Macrófagos , Macrófagos Alveolares/imunologia , Receptores Purinérgicos P2X7/metabolismo , Animais , Asma/patologia , Células Cultivadas , Feminino , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais
20.
J Surg Case Rep ; 2019(11): rjz305, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31723404

RESUMO

Lumbar spine fusion has become a common and effective procedure in orthopedic practice, and a spinal subdural hygroma development is a rare complication following this procedure. We report here the case of a revision lumbar spine fusion at levels L4-5, L5-S1, where the patient subsequently developed cauda equina syndrome 2 days post-operatively. Magnetic resonance imaging (MRI) showed a subdural, extra-arachnoid fluid collection from T12-L2, cephalad to the site of spine fusion. It appears the first case reported a subdural hygroma developed cephalad to the site of spine fusion. When a patient complains of radicular pain along with urinary retention and neurologic deficits post-lumbar spine surgery, cauda equina syndrome possibly caused by subdural hygroma should be considered. This warrants immediate MRI and emergent reoperation to relieve the pressure on the spinal cord may be necessary.

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