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1.
Front Immunol ; 12: 673693, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34408744

RESUMO

Background: Thymosin alpha 1 (Tα1) is widely used to treat patients with COVID-19 in China; however, its efficacy remains unclear. This study aimed to explore the efficacy of Tα1 as a COVID-19 therapy. Methods: We performed a multicenter cohort study in five tertiary hospitals in the Hubei province of China between December 2019 and March 2020. The patient non-recovery rate was used as the primary outcome. Results: All crude outcomes, including non-recovery rate (65/306 vs. 290/1,976, p = 0.003), in-hospital mortality rate (62/306 vs. 271/1,976, p = 0.003), intubation rate (31/306 vs. 106/1,976, p = 0.001), acute respiratory distress syndrome (ARDS) incidence (104/306 vs. 499/1,976, p = 0.001), acute kidney injury (AKI) incidence (26/306 vs. 66/1,976, p < 0.001), and length of intensive care unit (ICU) stay (14.9 ± 12.7 vs. 8.7 ± 8.2 days, p < 0.001), were significantly higher in the Tα1 treatment group. After adjusting for confounding factors, Tα1 use was found to be significantly associated with a higher non-recovery rate than non-Tα1 use (OR 1.5, 95% CI 1.1-2.1, p = 0.028). An increased risk of non-recovery rate associated with Tα1 use was observed in the patient subgroups with maximum sequential organ failure assessment (SOFA) scores ≥2 (OR 2.0, 95%CI 1.4-2.9, p = 0.024), a record of ICU admission (OR 5.4, 95%CI 2.1-14.0, p < 0.001), and lower PaO2/FiO2 values (OR 1.9, 95%CI 1.1-3.4, p = 0.046). Furthermore, later initiation of Tα1 use was associated with a higher non-recovery rate. Conclusion: Tα1 use in COVID-19 patients was associated with an increased non-recovery rate, especially in those with greater disease severity.


Assuntos
COVID-19/tratamento farmacológico , Síndrome do Desconforto Respiratório/epidemiologia , Timalfasina/efeitos adversos , Adulto , Idoso , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Prognóstico , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/prevenção & controle , Estudos Retrospectivos , Medição de Risco/estatística & dados numéricos , Timalfasina/administração & dosagem , Resultado do Tratamento
2.
Opt Lett ; 46(14): 3432-3435, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34264231

RESUMO

In this Letter, we demonstrate a high-power Raman fiber amplifier with excellent beam quality based on graded-index fiber. The Yb-doped fiber laser (YDFL) and bandwidth-tunable amplified spontaneous emission (ASE) source are employed as the pump source to compare the laser performance separately. When the ASE with a bandwidth of 8 nm is employed, a maximum power of 943 W at 1130 nm is achieved, which is twice that pumped by YDFL. The beam quality factor M2 at maximum output power is 1.6, with a brightness enhancement (BE) factor of 27. To the best of our knowledge, this is the best beam quality and BE factor based on pure Raman gain with output power of over 100 W.

3.
Clin Microbiol Infect ; 27(10): 1488-1493, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34020032

RESUMO

OBJECTIVES: Intravenous immunoglobulin (IVIG) is commonly used to treat severe COVID-19, although the clinical outcome of such treatment remains unclear. This study evaluated the effectiveness of IVIG treatment in severe COVID-19 patients. METHODS: This retrospective multicentre study evaluated 28-day mortality in severe COVID-19 patients with or without IVIG treatment. Each patient treated with IVIG was matched with one untreated patient. Logistic regression and inverse probability weighting (IPW) were used to control confounding factors. RESULTS: The study included 850 patients (421 IVIG-treated patients and 429 non-IVIG-treated patients). After matching, 406 patients per group remained. No significant difference in 28-day mortality was observed after IPW analysis (average treatment effect (ATE) = 0.008, 95% CI -0.081 to 0.097, p 0.863). There were no significant differences between the IVIG group and non-IVIG group for acute respiratory distress syndrome, diffuse intravascular coagulation, myocardial injury, acute hepatic injury, shock, acute kidney injury, non-invasive mechanical ventilation, invasive mechanical ventilation, continuous renal replacement therapy and extracorporeal membrane oxygenation except for prone position ventilation (ATE = -0.022, 95% CI -0.041 to -0.002, p 0.028). DISCUSSION: IVIG treatment was not associated with significant changes in 28-day mortality in severe COVID-19 patients. The effectiveness of IVIG in treating patients with severe COVID-19 needs to be further investigated through future studies.

4.
BMC Infect Dis ; 21(1): 398, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33926377

RESUMO

BACKGROUND: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening hyperinflammatory event and a fatal complication of viral infections. Whether sHLH may also be observed in patients with a cytokine storm induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still uncertain. We aimed to determine the incidence of sHLH in severe COVID-19 patients and evaluate the underlying risk factors. METHOD: Four hundred fifteen severe COVID-19 adult patients were retrospectively assessed for hemophagocytosis score (HScore). A subset of 7 patients were unable to be conclusively scored due to insufficient patient data. RESULTS: In 408 patients, 41 (10.04%) had an HScore ≥169 and were characterized as "suspected sHLH positive". Compared with patients below a HScore threshold of 98, the suspected sHLH positive group had higher D-dimer, total bilirubin, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, serum creatinine, triglycerides, ferritin, interleukin-6, C-reactive protein, procalcitonin, lactate dehydrogenase, creatine kinase isoenzyme, troponin, Sequential Organ Failure Assessment (SOFA) score, while leukocyte, hemoglobin, platelets, lymphocyte, fibrinogen, pre-albumin, albumin levels were significantly lower (all P < 0.05). Multivariable logistic regression revealed that high ferritin (>1922.58 ng/mL), low platelets (<101 × 109/L) and high triglycerides (>2.28 mmol/L) were independent risk factors for suspected sHLH in COVID-19 patients. Importantly, COVID-19 patients that were suspected sHLH positive had significantly more multi-organ failure. Additionally, a high HScore (>98) was an independent predictor for mortality in COVID-19. CONCLUSIONS: HScore should be measured as a prognostic biomarker in COVID-19 patients. In particular, it is important that HScore is assessed in patients with high ferritin, triglycerides and low platelets to improve the detection of suspected sHLH.


Assuntos
COVID-19/complicações , Linfo-Histiocitose Hemofagocítica/etiologia , Adulto , Idoso , Aspartato Aminotransferases/sangue , COVID-19/epidemiologia , COVID-19/terapia , China/epidemiologia , Comorbidade , Síndrome da Liberação de Citocina/complicações , Síndrome da Liberação de Citocina/virologia , Feminino , Ferritinas/sangue , Humanos , Incidência , Contagem de Linfócitos , Linfo-Histiocitose Hemofagocítica/epidemiologia , Linfo-Histiocitose Hemofagocítica/mortalidade , Masculino , Pessoa de Meia-Idade , Mortalidade , Estudos Retrospectivos , Fatores de Risco
5.
J Clin Invest ; 130(12): 6417-6428, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33141117

RESUMO

BACKGROUNDCorticosteroids are widely used in patients with COVID 19, although their benefit-to-risk ratio remains controversial.METHODSPatients with severe COVID-19-related acute respiratory distress syndrome (ARDS) were included from December 29, 2019 to March 16, 2020 in 5 tertiary Chinese hospitals. Cox proportional hazards and competing risks analyses were conducted to analyze the impact of corticosteroids on mortality and SARS-CoV-2 RNA clearance, respectively. We performed a propensity score (PS) matching analysis to control confounding factors.RESULTSOf 774 eligible patients, 409 patients received corticosteroids, with a median time from hospitalization to starting corticosteroids of 1.0 day (IQR 0.0-3.0 days) . As compared with usual care, treatment with corticosteroids was associated with increased rate of myocardial (15.6% vs. 10.4%, P = 0.041) and liver injury (18.3% vs. 9.9%, P = 0.001), of shock (22.0% vs. 12.6%, P < 0.001), of need for mechanical ventilation (38.1% vs. 19.5%, P < 0.001), and increased rate of 28-day all-cause mortality (44.3% vs. 31.0%, P < 0.001). After PS matching, corticosteroid therapy was associated with 28-day mortality (adjusted HR 1.46, 95% CI 1.01-2.13, P = 0.045). High dose (>200 mg) and early initiation (≤3 days from hospitalization) of corticosteroid therapy were associated with a higher 28-day mortality rate. Corticosteroid use was also associated with a delay in SARS-CoV-2 coronavirus RNA clearance in the competing risk analysis (subhazard ratio 1.59, 95% CI 1.17-2.15, P = 0.003).CONCLUSIONAdministration of corticosteroids in severe COVID-19-related ARDS is associated with increased 28-day mortality and delayed SARS-CoV-2 coronavirus RNA clearance after adjustment for time-varying confounders.FUNDINGNone.


Assuntos
Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , COVID-19/tratamento farmacológico , COVID-19/mortalidade , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/mortalidade , Idoso , COVID-19/complicações , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório/etiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Taxa de Sobrevida
6.
Respir Med ; 173: 106159, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33010731

RESUMO

BACKGROUND: The outbreak of COVID-19 caused by SARS-CoV-2 has been a pandemic. The objective of our study was to explore the association between sex and clinical outcomes in patients with COVID-19. METHODS: Detailed clinical data including clinical characteristics, laboratory tests, imaging features and treatments of 1190 cases of adult patients with confirmed COVID-19 were retrospectively analyzed. Associations between sex and clinical outcomes were identified by multivariable Cox regression analysis. RESULTS: There were 635 (53.4%) male and 555 (46.6%) female patients in this study. Higher rates of acute kidney injury (5.5% vs. 2.9%, p = 0.026), acute cardiac injury (9.1% vs. 4.3%, p = 0.001), and disseminated intravascular coagulation (2.5% vs. 0.7%, P = 0.024) were observed in males. Compared with female patients, male patients with COVID-19 had a higher inhospital mortality rate (15.7% vs. 10.3%, p = 0.005). However, Cox regression analysis showed that sex did not influence inhospital mortality of COVID-19 patients. CONCLUSIONS: Male sex was associated with a worse prognosis of COVID-19, but it seems not to be an independent prognostic factor.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Adulto , Idoso , COVID-19 , China , Infecções por Coronavirus/terapia , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Pandemias , Pneumonia Viral/terapia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Fatores Sexuais
7.
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.

8.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(5): 618-621, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32576358

RESUMO

Continuous renal replacement therapy (CRRT) has become an effective multiple organ support therapy instead of single renal replacement as initially expected, and it is widely used in intensive care unit (ICU). After the outbreak of coronavirus disease 2019 (COVID-19), a series of expert recommendation or consensus have been developed to diagnose and treat the disease, including CRRT in acute kidney injury (AKI) and hyper inflammatory response. However, CRRT in COVID-19 is extraordinarily different from regular one due to different pathophysiology and infectious clinical scenarios. Accordingly, the paper aims to elaborate the similarities and differences between CRRT in COVID-19 and routine treatment in terms of safety and accessibility, indications and timing, clinical operation, anticoagulation, fluid management, prevention and control of infectious diseases, etc.


Assuntos
Injúria Renal Aguda , Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , COVID-19 , Terapia de Substituição Renal Contínua , Humanos , Unidades de Terapia Intensiva , SARS-CoV-2
9.
Opt Express ; 28(8): 12395-12404, 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32403737

RESUMO

We comprehensively study the effects of temporal and spectral optimization on single-mode Raman fiber amplifiers. Amplified spontaneous emission sources and ytterbium-doped fiber lasers are employed as seed or pump lasers for comparison, and passive fibers are utilized as gain media. The influences of various parameters of the laser on 2nd order Raman threshold and maximum output power are investigated experimentally, including bandwidth, seed power, wavelength separation between pump and seed laser, and temporal stability. With the 190 m passive fiber, the output power increases from 99.5 W to 142.4 W, corresponding to 43.1% improvement through the optimization of seed laser power, pump wavelength and temporal performance of pump source in this amplifier, which has guidance on the establishment of high-power single-mode Raman fiber amplifiers.

10.
J Cell Mol Med ; 24(12): 6731-6740, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32383354

RESUMO

Sepsis is a life-threatening syndrome with a high risk of mortality, which is caused by the dysregulated host response to infection. We examined significant roles of circDMNT3B and miR-20b-5p in the intestinal mucosal permeability dysfunction of rats with sepsis. SD rats were randomly divided into 6 groups (n = 10/group): sham group, sepsis group, si-negative control group, circDNMT3B-si1 group, circDNMT3B-si2 group and circDNMT3B-si1 + anti-miR-20b-5p group. The level of malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, interleukin (IL)-6 and IL-10 levels were measured through ELISA assay kits. Cell survival rate and cell apoptosis were evaluated by Cell-Counting Kit-8 Assay and flow cytometry, respectively. Luciferase reporter assays were used to investigate interactions between miR-20b-5p circDMNT3B in HEK-293T cells. Silencing circDNMT3B can significantly increase the level of d-lactic acid, FD-40, MDA, diamine oxidase, IL-10 and IL-6, compared with sepsis group, while the SOD activity was lower. Silencing circDNMT3B leads to oxidative damage and influence inflammatory factors level in intestinal tissue. CircDNMT3B was identified as a target gene of miR-20b-5p. Silencing circDNMT3B decreased cell survival and induced apoptosis in Caco2 cells treated with LPS, which was reversed by anti-miR-20b-5p. MiR-20b-5p inhibitor remarkably down-regulated mentioned-above levels, in addition to up-regulate SOD activity, which may relieve the damage of intestinal mucosal permeability caused by silencing circDNMT3B in sepsis rats. Down-regulation of circDMNT3B was conducive to the dysfunction of intestinal mucosal permeability via sponging miR-20b-5p in sepsis rats, which may provide the novel strategy for sepsis treatment in the future.


Assuntos
Regulação para Baixo/genética , Mucosa Intestinal/fisiopatologia , MicroRNAs/metabolismo , RNA Circular/genética , Sepse/genética , Sepse/fisiopatologia , Animais , Apoptose/genética , Sequência de Bases , Células CACO-2 , Proliferação de Células/genética , Sobrevivência Celular/genética , Inativação Gênica , Humanos , Inflamação/genética , Inflamação/patologia , Mucosa Intestinal/patologia , Lipopolissacarídeos , Masculino , MicroRNAs/genética , Estresse Oxidativo/genética , Permeabilidade , RNA Circular/metabolismo , Ratos Sprague-Dawley
11.
Opt Lett ; 45(8): 2367-2370, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32287234

RESUMO

In this Letter, a high-power, high-brightness all-fiberized Raman amplifier based on a cladding-pumping scheme is presented for the first time, to the best of our knowledge. The triple-clad passive fiber is employed as Raman gain fiber in the laser system. The maximum output power is 762.6 W emitting at 1130 nm. To the best of our knowledge, this is the highest power in the fields of cladding-pumped Raman amplifiers. Through a cladding-pumping process, the beam quality parameter ${{\rm M}^2}$M2 improves from 6.12 of seed laser to 2.24 at maximum output power of 762.6 W, while the best ${{\rm M}^2}$M2 is 1.9 at 267.2 W. It is also the best beam quality of Raman laser with brightness enhancement in any kind of configuration (graded-index fiber or multi-clad fiber, laser or amplifier, all-fiber or free-space configuration) with power of over 100 W.

12.
Opt Express ; 28(3): 3495-3504, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32122016

RESUMO

In this paper, we study the power scaling in high power continuous-wave Raman fiber amplifier employing graded-index passive fiber. The maximum output power reaches 2.087 kW at 1130 nm with an optical conversion efficiency of 90.1% (the output signal power versus the depleted pump power). To the best of our knowledge, this is the highest power in the fields of Raman fiber lasers based merely on Stokes radiation. The beam quality parameter M2 improves from 15 to 8.9 during the power boosting process, then beam spot distortion appears at high power level. This is the first observation and analysis on erratic dynamic properties of the transverse modes in high power Raman fiber amplifier.

13.
Ann Intensive Care ; 10(1): 5, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31933054

RESUMO

BACKGROUND: Currently, there are no reliable predictors of risk of development and severity of acute kidney injury (AKI) in septic patients. The surfactant protein D (SP-D) polymorphism rs721917C/T is associated with a greater susceptibility to AKI in the Chinese population. Our aim was to evaluate the value of SP-D polymorphisms rs721917C/T and of plasma SP-D levels to predict the risk of development of AKI (defined with KDIGO criterion) in septic patients. METHODS: The study enrolled septic patients admitted to the Critical Care Department of two tertiary care hospitals. SP-D rs721917C/T polymorphisms were determined using the PCR-SSP method. Plasma SP-D and urine NGAL contents were measured using commercially available ELISA kits. RESULTS: 330 septic patients were included. Their SOFA scores were 12 ± 3. Patients with AKI (n = 156) had higher plasma SP-D levels (median: 153 ng/mL, range 111-198 ng/mL) and urinary NGAL levels (median: 575 ng/mL, range 423-727 ng/mL) than those without AKI (SP-D median: 124 ng/mL, range 81-159 ng/mL, P = 0.001; NGAL median: 484 ng/mL, range 429-573 ng/mL). Plasma SP-D levels of AKI patients were correlated with urinary NGAL contents (r = 0.853). In 32 patients receiving continuous renal replacement therapy (CRRT), plasma SP-D levels correlated with duration of CRRT (r = 0.448). The area under the receiver operating characteristic curve for plasma SP-D levels to predict AKI was 0.84. Patients with AKI had a higher rate of rs721917 CC genotype (AKI: 35% vs. non-AKI: 20%; P = 0.012), but a significantly lower rate of TT genotype (AKI: 19% vs. non-AKI: 26%; P = 0.005). SP-D rs721917 CC genotype was an independent predictor of AKI (P = 0.044) and mortality (P = 0.014). CONCLUSION: Our study showed that increased plasma SP-D level is associated with a higher risk of AKI in patients with sepsis. The SP-D rs721917CC genotype is an independent and significant predictor of AKI development and mortality of septic patients. The SP-D rs721917C/T polymorphisms should be further studied as diagnostic and prognostic biomarkers to facilitate early recognition of AKI.

14.
Appl Opt ; 58(35): 9728-9733, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31873575

RESUMO

Cascaded random Raman fiber lasers (CRRFLs) with simple configuration and high spectral purity have become a great candidate for power scaling over the 1.1 µm-2 µm spectral band. Recently, CRRFLs with high spectral purity over 90% have been proposed by applying a highly temporal-stable pump source or a free-space short-pass filter, at the cost of increased system complexity. In this work, pumped directly by a Yb-doped fiber oscillator at 1080 nm, an all-fiberized and simplified CRRFL with a short-pass optical filter based on bending fiber and a thin-film wavelength division multiplexer is demonstrated. The transmission loss of the filter for 5th Stokes order at 1440 nm is up to 70 dB. Spectral purity over 92% for all the first four Stokes orders is achieved. The highest output power is 15 W for the 4th Stokes order at 1341 nm.

15.
ACS Sens ; 4(12): 3298-3307, 2019 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-31769284

RESUMO

Viruses pose serious infectious disease threats to humans and animals. To significantly decrease the mortality and morbidity caused by virus infections, there is an urgent need of sensitive and rapid point-of-care platforms for virus detection, especially in low-resource settings. Herein, we developed a smartphone-based point-of-care platform for highly sensitive and selective detection of the avian influenza virus based on nanomaterial-enabled colorimetric detection. The 3D nanostructures, which serve as a scaffold for antibody conjugation to capture the avian influenza virus, are made on PDMS herringbone structures with a ZnO nanorod template. After virus capture, the on-chip gold nanoparticle-based colorimetric reaction allows virus detection by naked eyes with a detection limit of 2.7 × 104 EID50/mL, which is one order of magnitude better than that of conventional fluorescence-based ELISA. Furthermore, a smartphone imaging system with data processing capability further improves the detection limit, reaching down to 8 × 103 EID50/mL. The entire virus capture and detection process can be completed in 1.5 h. We envision that this point-of-care microfluidic system integrated with smartphone imaging and colorimetric detection would provide a fast, cheap, sensitive, and user-friendly platform for virus detection in low-resource settings.


Assuntos
Colorimetria/métodos , Vírus da Influenza A Subtipo H5N2/isolamento & purificação , Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas/métodos , Nanotubos/química , Smartphone , Colorimetria/instrumentação , Dimetilpolisiloxanos/química , Desenho de Equipamento , Ouro/química , Limite de Detecção , Nanopartículas Metálicas/química , Técnicas Analíticas Microfluídicas/instrumentação , Testes Imediatos , Óxido de Zinco/química
16.
Chin Med J (Engl) ; 132(10): 1179-1187, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31140989

RESUMO

BACKGROUND: Antibiotics are frequently used to treat critically ill patients, and its use is often accompanied by intestinal dysbiosis that might further lead to bacterial translocation (BT). Nevertheless, studies on the relationship between antibiotic therapy and BT are rare. In the present study, we investigated the effect of broad-spectrum antibiotics on BT in an experimental rat model of burn or sepsis injury. METHODS: The septic rat model was simulated by a second insult with lipopolysaccharides after burn injury. Ninety-two male Sprague-Dawley rats were randomly divided into control, burn, and sepsis groups (n = 8 or 9, each group), and the latter two groups were then treated with imipenem or ceftriaxone for 3 or 9 days. The mesenteric lymph nodes, liver, lungs, and blood were collected at each time point under sterile conditions for quantitative bacterial culture and strain identification. The differences between the groups were compared by Fisher exact test or Mann-Whitney U test. RESULTS: Only minimal Escherichia coli translocation to the mesenteric lymph nodes was observed in the normal control group, in which the BT rate was 12.5%. Burn injury did not affect the BT rate (Burn group vs. Control group, 12.5% vs. 12.5%, P = 1.000), whereas the BT rate showed an increased trend after the second insult with lipopolysaccharide (Sepsis group vs. Control group, 44.4% vs. 12.5%, P = 0.294), and many strains of Enterobacteria spp. were detected in distant organs (liver, lung, and blood) [Sepsis group vs. Control group, 0 (0,3) vs. 0 (0,0), U = 20, P = 0.045]. After the antibiotic treatment, BT to the distant organs was increased in burned rats [Burn IT3 group vs. Burn group, 0 (0,2) vs. 0 (0,0); Burn IT9 group vs. Burn group, 0 (0,1) vs. 0 (0,0); Burn CT9 group vs. Burn group, 0 (0,2) vs. 0 (0,0); all U = 20 and P = 0.076] but decreased in septic rats [Sepsis CT3 group vs. Sepsis group, 0 (0,0) vs. 0 (0,3), U = 20, P = 0.045]. The total amount of translocated bacteria, regardless of which antibiotic was used, was increased in burned rats [Burn IT9 group vs. Burn group, 2.389 (0,2.845) vs. 0 (0,2.301) Log10 colony-forming units (CFU)/g, U = 14, P = 0.034; Burn CT3 group vs. Burn group, 2.602 (0,3.633) vs. 0 (0,2.301) Log10 CFU/g, U = 10.5, P = 0.009], but there was a slightly decreased trend in septic rats [Sepsis IT9 group vs. Sepsis group, 2.301 (2,3.146) vs. 0 (0,4.185) Log10 CFU/g, U = 36, P = 0.721; Sepsis CT9 group vs. Sepsis group, 2 (0,3.279) vs. 0 (0,4.185) Log10 CFU/g, U = 32.5, P = 0.760]. Remarkably, the quantity of Enterococci spp. dramatically increased after broad-spectrum antibiotic treatment in both the burned and septic groups [Burn IT3 group vs. Burn group, 1 (0,5.164) vs. 0 (0,0) Log10 CFU/g, U = 16; Burn IT9 group vs. Burn group, 1 (0,2.845) vs. 0 (0,0) Log10 CFU/g, U = 16; Burn CT3 group vs. Burn group, 2.602 (0,3.633) vs. 0 (0,0) Log10 CFU/g, U = 8; Burn CT9 group vs. Burn group, 1 (0,4.326) vs. 0 (0,0) Log10 CFU/g, U = 16; Sepsis IT3 group vs. Sepsis group, 2.477 (0,2.903) vs. 0 (0,0) Log10 CFU/g, U = 4.5; Sepsis IT9 group vs. Sepsis group, 2 (0,3.146) vs. 0 (0,0) Log10 CFU/g, U = 9; Sepsis CT3 group vs. Sepsis group, 1.151 (0,2.477) vs. 0 (0,0) Log10 CFU/g, U = 18; Sepsis CT9 group vs. Sepsis group, 2 (0,3) vs. 0 (0,0) Log10 CFU/g, U = 13.5; all P < 0.05]. CONCLUSIONS: Broad-spectrum antibiotics promote BT in burned rats but prevent BT in septic rats, especially preventing BT to distant organs, such as the liver and lung. Moreover, Enterococci spp. with high drug resistance and high pathogenicity translocated most after antibiotic treatment.


Assuntos
Antibacterianos/uso terapêutico , Translocação Bacteriana/efeitos dos fármacos , Queimaduras/tratamento farmacológico , Queimaduras/microbiologia , Sepse/tratamento farmacológico , Sepse/microbiologia , Animais , Escherichia coli/efeitos dos fármacos , Escherichia coli/patogenicidade , Fígado/microbiologia , Pulmão/microbiologia , Linfonodos/microbiologia , Masculino , Ratos , Ratos Sprague-Dawley
17.
Chin Med J (Engl) ; 132(10): 1188-1193, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31140990

RESUMO

BACKGROUND: It is important to modulate the expression of glucocorticoids receptor (GR) in tress and maintain the immunity homeostasis in sepsis process. Rhubarb have been shown to have potential effects on anti-inflammatory and immune modulation. The present study was designed to investigate the effects of rhubarb on the expression of GR and cellular immunity in burn-induced septic rats. METHODS: Sixty-six healthy male Sprague Dawley (SD) rats were randomized into sepsis group (n = 24), rhubarb group (n = 24), and control group (n = 18); each group were further randomized into 12, 24, and 72 h subgroups according to different time points. During onset of the sepsis model, the rats in the rhubarb group were infused with 50 mg/kg rhubarb powder dissolved into 1 mL saline through gastric tube, while sepsis and control groups were treated with saline. The binding activity of GR in liver cytosol and binding capacity of GR in peripheral blood leucocyte were analyzed by radiation ligands binding assay. The percentages of CD4,CD8,CD4CD25T cells, CD19B cells as well as natural killer (NK) cells in the lymphocytes in peripheral blood were detected by flow cytometer. For assessing the differences among groups, one-way analysis of variance (ANOVA) with Scheffe multi-comparison techniques were employed. Comparisons between time-based measurements within each group were performed with ANOVA repeated measurement. RESULTS: The binding activity of GR in liver cytosol and binding capacity of GR in peripheral blood leucocyte were significantly decreased in a time-dependent manner in sepsis group (t = 23.045, P < 0.01; t = 24.395, P < 0.05, respectively), which were increased in a time-dependent manner after rhubarb administration (t = 19.965, P < 0.05; t = 17.140, P < 0.05, respectively). Twelve hours after sepsis, the percentages of CD4 T cells, CD4/CD25 T cell ratio, and CD19 B cells in the peripheral blood were significantly increased in the sepsis group (t = -3.395, P < 0.01; t = 2.568, P < 0.05; t = 2.993, P < 0.05, vs. control mice, respectively). However, the percentage of NK cells in the peripheral blood were significantly decreased in the sepsis group (t = -2.022, P < 0.05, vs. control mice). Twelve hours after sepsis, the percentage of CD8 T cells were significantly decreased in the peripheral blood in the sepsis group (t = -2.191, P < 0.05, vs. control mice) and were significantly increased in the rhubarb group (t = 2.953, P < 0.05, vs. sepsis mice). Seventy-two hours after sepsis, the ratio of CD4/CD25 T cell in peripheral blood were significantly increased in the sepsis group (t = 2.508, P < 0.05, vs. control mice) while were significantly decreased in the rhubarb group (t = 3.378, P < 0.05, vs. control mice). Furthermore, the percentages of CD19 B cell in peripheral blood were significantly decreased at 72 h in the rhubarb group (t = 2.041, P < 0.05 vs. sepsis group). CONCLUSIONS: Rhubarb might play potential anti-inflammatory and immunomodulatory roles in the sepsis processes.


Assuntos
Queimaduras/tratamento farmacológico , Queimaduras/metabolismo , Imunidade Celular/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Receptores de Glucocorticoides/metabolismo , Rheum/química , Sepse/tratamento farmacológico , Sepse/metabolismo , Análise de Variância , Animais , Anti-Inflamatórios/uso terapêutico , Linfócitos B/metabolismo , Queimaduras/imunologia , Antígenos CD4/metabolismo , Citometria de Fluxo , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Células Matadoras Naturais/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Sepse/imunologia , Linfócitos T/metabolismo , Linfócitos T Reguladores/metabolismo
18.
Small ; 14(44): e1802899, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30286282

RESUMO

The mechanism of cells passing through microconstrictions, such as capillaries and endothelial junctions, influences metastasis of circulating tumor cells (CTCs) in vivo, as well as size-based enrichment of CTCs in vitro. However, very few studies observe such translocation of microconstrictions in real time, and thus the inherent biophysical mechanism is poorly understood. In this study, a multiplexed microfluidic device is fabricated for real-time tracking of cell translocation under physiological pressure and recording deformation of the whole cell and nucleus, respectively. It is found that the deformability and size of the nucleus instead of the whole cell dominate cellular translocation through microconstrictions under a normal physiological pressure range. More specifically, cells with a large and stiff nucleus are prone to be blocked by relatively small constrictions. The same phenomenon is also observed in the size-based enrichment of CTCs from peripheral blood of metastatic cancer patients. These findings are different from a popular viewpoint that the size and deformability of a whole cell mainly determine cell translation through microconstrictions, and thus may elucidate interactions between CTCs and capillaries from a new perspective and guide the rational design of size-based microfilters for rare cell enrichment.


Assuntos
Biomimética/métodos , Núcleo Celular/metabolismo , Humanos , Dispositivos Lab-On-A-Chip , Metástase Neoplásica/patologia , Células Neoplásicas Circulantes/patologia
19.
J Nutr Biochem ; 53: 66-71, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29195132

RESUMO

The choroid plexus is able to modulate the cognitive function, through changes in the neuroinflammatory response and in brain immune surveillance. However, whether lycopene is involved in inflammatory responses at the choroid plexus in the early stages of Alzheimer's disease, and its molecular underpinnings are elusive. In this rat study, lycopene was used to investigate its protective effects on inflammation caused by ß-amyloid. We characterized the learning and memory abilities, cytokine profiles of circulating TNF-α, IL-1ß and IL-6ß in the serum and the expressions of Toll like receptor 4 and nuclear factor-κB p65 mRNA and protein at the choroid plexus. The results showed that functional deficits of learning and memory in lycopene treatment groups were significantly improved compared to the control group without lycopene treatment in water maze test. The levels of serum TNF-α, IL-1ß and IL-6ß were significantly increased, and the expressions of TLR4 and NF-κB p65 mRNA and protein at the choroid plexus were up-regulated, indicating inflammation response was initiated following administration of Aß1-42. After intragastric pretreatment with lycopene, inflammatory cytokines were significantly reduced and lycopene also reversed the Aß1-42 induced up-regulation of TLR4 and NF-κB p65 mRNA and protein expressions at the choroid plexus. These results provided a novel evidence that lycopene significantly improved cognitive deficits and were accompanied by the attenuation of inflammatory injury via blocking the activation of NF-κB p65 and TLR4 expressions and production of cytokines, thereby endorsing its usefulness for diminishing ß-amyloid deposition in the hippocampus tissues.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Plexo Corióideo/efeitos dos fármacos , Licopeno/farmacologia , NF-kappa B/metabolismo , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/toxicidade , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Plexo Corióideo/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Citocinas/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , NF-kappa B/genética , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/toxicidade , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
20.
Sci Rep ; 7: 42402, 2017 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-28181571

RESUMO

We demonstrated a high-power continuous-wave (CW) dual-wavelength Ho-doped fiber laser (HDFL) at 2049 nm and 2153 nm with a simple coupled-cavity configuration. A ~100 W laser diode-pumped fiber laser at 1150 nm served as the pump source. The maximum output power reached ~22.3 W and the slope efficiency was 23%. By altering the incident pump power, the power ratio of two signal wavelengths could be tuned in a large range due to gain competition. As far as we know, this is the first CW dual-wavelength HDFL with the power exceeding ten-watt-level, and the first dual-wavelength HDFL with the central wavelengths exceeding 2.0 µm and 2.15 µm respectively.

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