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1.
Genes Dev ; 35(7-8): 528-541, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33737385

RESUMO

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers worldwide and evolves often to lung metastasis. P53R175H (homologous to Trp53 R172H in mice) is a common hot spot mutation. How metastasis is regulated by p53R175H in ESCC remains to be investigated. To investigate p53R175H-mediated molecular mechanisms, we used a carcinogen-induced approach in Trp53R172H/- mice to model ESCC. In the primary Trp53R172H/- tumor cell lines, we depleted Trp53R172H (shTrp53) and observed a marked reduction in cell invasion in vitro and lung metastasis burden in a tail-vein injection model in comparing isogenic cells (shCtrl). Furthermore, we performed bulk RNA-seq to compare gene expression profiles of metastatic and primary shCtrl and shTrp53 cells. We identified the YAP-BIRC5 axis as a potential mediator of Trp53 R172H -mediated metastasis. We demonstrate that expression of Survivin, an antiapoptotic protein encoded by BIRC5, increases in the presence of Trp53R172H Furthermore, depletion of Survivin specifically decreases Trp53R172H-driven lung metastasis. Mechanistically, Trp53R172H but not wild-type Trp53, binds with YAP in ESCC cells, suggesting their cooperation to induce Survivin expression. Furthermore, Survivin high expression level is associated with increased metastasis in several GI cancers. Taken together, this study unravels new insights into how mutant p53 mediates metastasis.

2.
BMC Infect Dis ; 21(1): 147, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33546633

RESUMO

BACKGROUND: Coronavirus disease 2019(COVID-19) has spread worldwide. The present study aimed to characterize the clinical features and outcomes of imported COVID-19 patients with high body mass index (BMI) and the independent association of BMI with disease severity. METHODS: In this retrospective cohort study, 455 imported COVID-19 patients were admitted and discharged in Zhejiang province by February 28, 2020. Epidemiological, demographic, clinical, laboratory, radiological, treatment, and outcome data were collected, analyzed and compared between patients with BMI ≥ 24and < 24. RESULTS: A total of 268 patients had BMI < 24, and 187 patients had BMI ≥ 24. Those with high BMI were mostly men, had a smoking history, fever, cough, and sputum than those with BMI < 24. A large number of patients with BMI ≥ 24 were diagnosed as severe/critical types. Some biochemical indicators were significantly elevated in patients with BMI ≥ 24. Also, acute liver injury was the most common complication in these patients. The median days from illness onset to severe acute respiratory syndrome coronavirus 2 detection, duration of hospitalization, and days from illness onset to discharge were significantly longer in patients with BMI ≥ 24 than those with BMI < 24. High BMI, exposure to Wuhan, any coexisting medical condition, high temperature, C-reactive protein (CRP), and increased lactate dehydrogenase (LDH) were independent risk factors for severe/critical COVID-19. After adjusting for age, sex and above factors, BMI was still independently associated with progression to severe/critical illness (P = 0.0040). Hemoglobin, alanine aminotransferase (ALT), CRP, and serum creatinine (Scr) were independent risk factors associated with high BMI. CONCLUSIONS: Contrasted with the imported COVID-19 patients with BMI < 24, high proportion of COVID-19 patients with BMI ≥ 24 in our study, especially those with elevated CRP and LDH, developed to severe type, with longer hospitalization duration and anti-virus course. Thus, high BMI is a risk factor for the progression and prognosis of imported COVID-19.


Assuntos
/epidemiologia , Adulto , Índice de Massa Corporal , China/epidemiologia , Estudos de Coortes , Progressão da Doença , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
3.
Arch Virol ; 166(4): 1113-1124, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33576898

RESUMO

Avian influenza virus (AIV), Newcastle disease virus (NDV), and avian infectious bronchitis virus (IBV) inflict immense damage on the global poultry industry annually. Serological diagnostic methods are fundamental for the effective control and prevention of outbreaks caused by these viruses. In this study, a novel triplex protein microarray assay was developed and validated for the rapid and simultaneous visualized detection of antibodies against AIV, NDV, and IBV in chicken sera. The AIV nuclear protein (NP), NDV phosphoprotein (P), and IBV nonstructural protein 5 (nsp5) were produced in a prokaryotic expression system, purified, and immobilized onto an initiator integrated poly(dimethylsiloxane) (iPDMS) film as probes to detect antibodies against these viruses in chicken sera. After optimization of the reaction conditions, no cross-reactivity was detected with infectious bursal disease virus, avian leukosis virus subgroup J and chicken anemia virus antisera. The lowest detectable antibody titers in this assay corresponded to hemagglutination inhibition (HI) titers of 24 and 21 for AIV and NDV, respectively, and to an IDEXX antibody titer of 103 for IBV, using the HI assay and IDEXX commercial ELISA kit as the reference methods. When156 serum samples were tested using the new assay, the HI test and the IBV IDEXX ELISA kit, the assay showed 96.8% (151/156), 97.4% (152/156) and 99.4% (155/156) diagnostic accuracy for detection of AIV, NDV and IBV antibody, respectively. The current study suggests that the newly developed triplex microarray is rapid, sensitive, and specific, providing a viable alternative assay for AIV, NDV, and IBV antibody screening in epidemiological investigations and vaccination evaluations.


Assuntos
Anticorpos Antivirais/sangue , Vírus da Bronquite Infecciosa/isolamento & purificação , Vírus da Influenza A/isolamento & purificação , Vírus da Doença de Newcastle/isolamento & purificação , Doenças das Aves Domésticas/diagnóstico , Análise Serial de Proteínas/veterinária , Animais , Antígenos Virais/genética , Antígenos Virais/imunologia , Antígenos Virais/metabolismo , Galinhas , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/veterinária , Imunoensaio/normas , Imunoensaio/veterinária , Vírus da Bronquite Infecciosa/imunologia , Vírus da Influenza A/imunologia , Influenza Aviária/diagnóstico , Doença de Newcastle/diagnóstico , Vírus da Doença de Newcastle/imunologia , Doenças das Aves Domésticas/virologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Sensibilidade e Especificidade , Testes Sorológicos/normas , Testes Sorológicos/veterinária
4.
Gerontology ; : 1-12, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33406518

RESUMO

OBJECTIVE: We aim to investigate the clinical characteristics and risk factors for the severe cases of coronavirus disease 2019 (COVID-19) in comparison with the non-severe patients. METHODS: We searched PubMed, EMBASE, Web of Science, and CNKI to collect all relevant studies published before July 26, 2020, and a total of 30 papers were included in this meta-analysis. RESULTS: In the severe COVID-19 patients, 60% (95% CI = 56-64%) were male, 25% (95% CI = 21-29%) were over 65 years old, 34% (95% CI = 24-44%) were obese, and 55% (95% CI = 41-70%) had comorbidities. The most prevalent comorbidities were hypertension (34%, 95% CI = 25-44%), diabetes (20%, 95% CI = 15-25%), and cardiovascular disease (CVD; 12%, 95% CI = 9-16%). The most common blood test abnormalities were elevated C-reactive protein (CRP; 87%, 82-92%), decreased lymphocyte count (68%, 58-77%), and increased lactate dehydrogenase (69%, 95% CI = 57-81%). In addition, abnormal laboratory findings revealing organ dysfunctions were frequently observed in the severe cases, including decrease in albumin (43%, 95% CI = 24-63%) and increase in aspartate aminotransferase (47%, 95% CI = 38-56%), alanine aminotransferase (28%, 95% CI = 16-39%), troponin I/troponin T (TnI/TnT; 29%, 95% CI = 13-45%), and serum Cr (SCr; 10%, 95% CI = 5-15%). CONCLUSION: The male, elderly and obese patients and those with any comorbidities, especially with hypertension, diabetes, and CVD, were more likely to develop into severe cases. But the association between hypertension, diabetes, CVD, and severity of COVID-19 was declined by the increase of age. A significant elevation in cardiac TnI/TnT, the hepatic enzymes, and SCr and the reduction in lymphocytes with elevated CRPs are important markers for the severity. Specific attention should be given to the elderly male and obese patients and those with indications of severe immune injury in combination with bacterial infection and indication of multi-organ dysfunction or damages.

5.
Lab Med ; 52(1): e8-e14, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33395698

RESUMO

OBJECTIVE: A positive result of SARS-CoV-2 nucleic acid detection provides critical laboratory evidence for clinical confirmed diagnosis, pandemic status evaluation, a pandemic prevention plan, treatment of infected people with symptoms, and protection of uninfected people. This study aims to provide a practical reference for SARS-CoV-2 nucleic acid-related research and detection. METHODS: Our laboratory has established policies combining personnel management and quality control practices for SARS-CoV-2 nucleic acid detection during the pandemic. RESULTS: In this article, we describe cross-department personnel management and key points of personal protection and quality control in the testing process. We also report on the differences in detection and the compatibility between different brand kits. CONCLUSION: It is critical to maintain a standard and accurate laboratory operation for nucleic acid testing.


Assuntos
/normas , /epidemiologia , Pandemias , RNA Viral/genética , /genética , /virologia , Humanos , Variações Dependentes do Observador , Equipamento de Proteção Individual/provisão & distribução , Administração de Recursos Humanos/métodos , Garantia da Qualidade dos Cuidados de Saúde/métodos , Controle de Qualidade , Kit de Reagentes para Diagnóstico
6.
Chin Med J (Engl) ; 133(23): 2816-2821, 2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-33273330

RESUMO

BACKGROUND: The optimal surgical approach for four-level cervical spondylotic myelopathy remains controversial. The purpose of this study was to compare clinical and radiological outcomes and complications between the anterior and posterior approaches for four-level cervical spondylotic myelopathy. METHODS: A total of 19 patients underwent anterior decompression and fusion and 25 patients underwent posterior laminoplasty and instrumentation in this study. Perioperative information, intraoperative blood loss, clinical and radiological outcomes, and complications were recorded. Japanese Orthopedic Association (JOA) score, 36-item short form survey (SF-36) score and cervical alignment were assessed. RESULTS: There were no significant differences in JOA scores between the anterior and posterior group preoperatively (11.6 ±â€Š1.6 vs. 12.1 ±â€Š1.5), immediately postoperatively (14.4 ±â€Š1.1 vs. 13.8 ±â€Š1.3), or at the last follow-up (14.6 ±â€Š1.0 vs. 14.2 ±â€Š1.1) (P > 0.05). The JOA scores significantly improved immediately postoperatively and at the last follow-up in both groups compared with their preoperative values. The recovery rate was significantly higher in the anterior group both immediately postoperatively and at the last follow-up. The SF-36 score was significantly higher in the anterior group at the last follow-up compared with the preoperative value (69.4 vs. 61.7). Imaging revealed that there was no significant difference in the Cobb angle at C2-C7 between the two groups preoperatively (-2.0°â€Š±â€Š7.3° vs. -1.4°â€Š±â€Š7.5°). The Cobb angle significantly improved immediately postoperatively (12.3°â€Š±â€Š4.2° vs. 9.2°â€Š±â€Š3.6°) and at the last follow-up (12.4°â€Š±â€Š3.5° vs. 9.0°â€Š±â€Š2.6°) in both groups compared with their preoperative values (P = 0.00). Three patients had temporary dysphagia in the anterior group and four patients had persistent axial symptoms in the posterior group. CONCLUSIONS: Both the anterior and posterior approaches were effective in treating four-level cervical spondylotic myelopathy in terms of neurological clinical outcomes and radiological features. However, the JOA score recovery rate and SF-36 score in the anterior group were significantly higher. Persistent axial pain could be a major concern when undertaking the posterior approach.

7.
Semin Oncol ; 2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-33334607

RESUMO

INTRODUCTION: SARS-CoV-2 (S-2) infection duration and its impact on patients with cancer and mild to moderate COVID-19 undergoing cancer-directed therapy (CDT), especially in the underserved population, is not well described. We conducted a retrospective study to analyze S-2 positive (+) patients on CDT to describe the S-2 duration and its impact on CDT. METHODS: Two hundred ninety-nine patients with cancer were tested with nasopharyngeal (NP) S-2 PCR assay at Columbia University Medical Irving Center (CUIMC), a Minority-NCI Community Oncology site, of which 77 (26%) tested positive. We retrospectively analyzed 26 S-2 (+) patients with mild-to-moderate COVID-19 receiving CDT who consented to the study. NP PCR was repeated every 1 to 2 weeks until 2 successive negative (-) PCRs were obtained prior to restarting CDT. Time to 2 (-) PCR and serology results were recorded. Cycling thresholds (Ct) were obtained for S-2 specific targets and represented an indirect measure of viral load. RESULTS: Demographics of N = 26 patients are: Hispanic (N = 17, 65%), Black (N = 1, 4%), White (N = 7, 27%), and undeclared (N = 1, 4%). Among the tumor histologies represented, gastrointestinal (N = 9, 35%), breast (N = 5, 19%), and sarcoma (N = 3, 12%) were most common. Median time to 2 (-) PCR was 32 days. Twenty patients required greater than 14 days to achieve 2 sequential (-) swabs. CDT was delayed in 21 patients (81%) of whom three experienced disease progression, likely attributed to an interruption in CDT, which was delayed by a mean of 53 days. Interestingly, nine (41%) patients had Ct values greater than 34 for the pan SARS target and seven (32%) patients had Ct values greater than 34 for the SARS-COV-2 target. Sixteen of 16 patients on CDT, tested positive for IgG antibodies at the time of consent, despite protracted viral detectability by NP PCR. CONCLUSION: Patients receiving CDT appear to have prolonged detectable S-2 by PCR, which can lead to interruption of CDT and POD in patients. We believe and recommend that patients with asymptomatic to mild COVID-19 and aggressive malignancies are at greatest risk for cancer related morbidity and mortality due to CDT cessation and should be considered for continued CDT without interruption. Ct values and serology testing are tools that can help identify those patients on CDT who may be at greatest risk of worsening COVID-19 or of spreading S-2.

8.
Chin Med J (Engl) ; 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33252379

RESUMO

BACKGROUND: Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs. METHODS: We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%. RESULTS: At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group. CONCLUSIONS: The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx.

9.
J Int Med Res ; 48(11): 300060520969582, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33179557

RESUMO

OBJECTIVE: Liver inflammatory activity staging is critical to guide the treatment of chronic hepatitis B virus (CHB) infection. Here, we aimed to identify practical clinical biomarkers of moderate inflammatory activity in hepatitis B e-antigen (HBeAg)-negative CHB patients. METHODS: Treatment-naïve HBeAg-negative CHB patients who underwent liver biopsy at our hospital from 1 January 2013 to 31 December 2016 were enrolled. Markers of inflammatory activity were analyzed using binary logistic regression. The area under the receiver operator characteristic curve (AUROCC) was used to assess diagnostic accuracy. RESULTS: A total of 106 HBeAg-negative treatment-naive CHB patients were enrolled. According to their METAVIR inflammatory scores, 30.2% of patients were in stage ≥A2. Total triiodothyronine (TT3) and hepatitis B virus (HBV) DNA levels were predictors of moderate inflammatory activity (A ≥ 2). The AUROCCs of TT3 and HBV DNA levels were 0.651 and 0.797, respectively. The optimal cut-off values for TT3 and HBV DNA were 1.755 nmol/L and 4.61 log10 IU/mL, respectively. CONCLUSIONS: A sizable proportion of treatment-naive HBeAg-negative CHB patients required antiviral treatment (30.2%) after undergoing liver biopsy. TT3 and HBV DNA helps identify patients with moderate inflammatory activity (A ≥ 2), potentially reducing the need for liver biopsies and helping guide treatment of CHB patients.

10.
Gynecol Oncol ; 159(3): 744-750, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33019982

RESUMO

OBJECTIVE: We used a novel machine learning algorithm to develop a precision prognostication system for endometrial cancer. METHODS: The Ensemble Algorithm for Clustering Cancer Data (EACCD) unsupervised machine learning algorithm was applied to women with endometrioid endometrial cancer in the Surveillance, Epidemiology, and End Results database from 2004 to 2015. The prognostic system was created based on TNM stage, grade, and age. The concordance (C-index) was used to cut dendrograms and create prognostic groups. Kaplan-Meier cancer-specific survival was employed to visualize the survival function of EACCD-based prognostic groups and AJCC groups. RESULTS: A total of 46,773 women were identified. Using the machine learning algorithm with TNM stage, grade, and three age groups, eleven prognostic groups were generated with a C-index of 0.8380. The five-year survival rates for the eleven groups ranged from 37.9-99.8%. To simplify the classification system further, using visual inspection of the data we created a modified EACCD grouping, and combined the top six survival groups into three new prognostic groups. The new five-year survival rates for these eight modified prognostic groups included: 99.1% for group 1, 96.5% for group 2, 92.2% for group 3, 84.8% for group 4, 72.7% for group 5, 61.1% for group 6, 52.6% for group 7, and 37.9% for group 8. The C-index for the modified eight prognostic groups was 0.8313. CONCLUSION: This novel machine learning algorithm demonstrates improved prognostic prediction for patients with endometrial cancer. Using machine learning for endometrial cancer allows for the integration of multiple factors to develop a precision prognostication system.

11.
ACS Appl Mater Interfaces ; 12(42): 47854-47864, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33045826

RESUMO

Multifunctional silica-based aerogels are an emerging material due to their unique properties and wide applications. However, their large-scale production and application are limited due to the high cost and cumbersome preparation process. Herein, we prepare graphene oxide (GO)/silica-based composite aerogels via a simple in situ sol-gel reaction. GO nanosheets (GOs) are functionalized with polyethylenimine (PEI) and 3-glycidyloxypropyltrimethoxysilane (GPTMS) successively. After a cohydrolysis and condensation of trimethoxymethylsilane (MTMS) and dimethoxydimethylsilane (DMDMS) in the presence of GOs and a convenient ambient-pressure drying process, the composite aerogels are obtained. In addition to the normal cross-linking of MTMS and DMDMS, the GOs also behave as cross-linking points to significantly enhance the mechanical properties and thermal stability of the network of the composite aerogels. The pore structure of the aerogels is tailored by varying the GO loads as well as its surface modification. The Young's modulus of a composite aerogel with a GO load of 0.5 wt % is about 5 times that for a neat polysiloxane aerogel, and the maximum degradation rate temperature is increased to over 90 °C. Compared with pure polysiloxane aerogel, the thermal insulation and flame resistance are also improved by a small addition of GOs. Moreover, GO/silica-based composite aerogels show stable piezo-resistive behavior. With the excellent mechanical properties, thermal stability, and multifunctionality, GO/silica-based composite aerogels show promising applications under some harsh and extreme conditions.

12.
Eur Spine J ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33091143

RESUMO

BACKGROUND: To compare clinical effect and safety between posterior fossa decompression with duraplasty (PFDD) and posterior fossa decompression without duraplasty (PFD) in treatment of Chiari type I malformation and basilar impression. METHODS: A comprehensive computer search was conducted from 2000 to 2019. The quality assessment was performed by the QUADAS-2 tool. The clinical value of comparison between PFDD and PFD was evaluated by using the pooled estimate of sensitivity and specificity. In addition, sensitivity analysis and bias analysis were applied to ensure the accuracy of the results. RESULTS: Finally, 468 patients were enrolled in 6 studies and ultimately met the eligibility criteria. The PFDD and PFD groups were 282 and 186, respectively. The meta-analysis showed no significant difference in the Chicago Chiari Outcome Scale (COSS score) (MD = 0.14, 95% CI [-0.23, 0.50], P = 0.47; P = heterogeneity = 0.86, I2 = 0%). Meanwhile, Significant difference existed in length of stay (MD = -1.08, 95% CI [-1.32, -0.84], P = 0.001; heterogeneity P < 0.000001, I2 = 85%) and complications (OR = 0.35, 95%CI [0.20, 0.62], P = 0.0003; P for Heterogeneity = 0.04, I2 = 56%). CONCLUSION: PFD is a more efficient and safer therapy than PFDD in the treatment of Chiari type I malformation with basilar impression.

13.
Stat Methods Med Res ; : 962280220951907, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867604

RESUMO

RNA sequencing data have been abundantly generated in biomedical research for biomarker discovery and other studies. Such data at the exon level are usually heavily tailed and correlated. Conventional statistical tests based on the mean or median difference for differential expression likely suffer from low power when the between-group difference occurs mostly in the upper or lower tail of the distribution of gene expression. We propose a tail-based test to make comparisons between groups in terms of a specific distribution area rather than a single location. The proposed test, which is derived from quantile regression, adjusts for covariates and accounts for within-sample dependence among the exons through a specified correlation structure. Through Monte Carlo simulation studies, we show that the proposed test is generally more powerful and robust in detecting differential expression than commonly used tests based on the mean or a single quantile. An application to TCGA lung adenocarcinoma data demonstrates the promise of the proposed method in terms of biomarker discovery.

14.
Cell Death Dis ; 11(8): 691, 2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32826849

RESUMO

Endoplasmic reticulum stress (ER stress) just like a double-edged sword depending on different conditions in the development of multiple hepatic diseases. But the molecular mechanisms of functional conversion during ER stress have not been fully elucidated. In this study, we aim to illustrate the role of PPARα and the subtle mechanism in the functional conversion of ER stress. Tunicamycin (TM) and thapsigargin (TG), as ER stress inducers, were used to induce ER stress in AML12 cells. During the ER stress, qRT-PCR and immunoblotting was used to measure the expression levels of GRP78 and CHOP which show a gradually increasing trend, while PPARα and autophagy was significantly activated in the early stage but was inhibited in the late stage. Moreover, PPARα inhibition by siRNA promoted cell injury in the mild-ER stress and PPARα activation by WY-14643 reduced cell apoptosis in the serious ER stress. In the mild-ER stress with PPARα knocked down, activation of autophagy by rapamycin significantly improved cell survival, in the serious ER stress with PPARα activation, inhibition of autophagy by 3-MA aggravate cell injury. In addition, in the mild-ER stress with PPARα knocked down, CHOP knocked down by siRNA reduced cell apoptosis, in the serious ER stress activated PPARα, CHOP over-expression mediated by lentiviral vector contributed to serious cell injury. Furthermore, C57BL/6 mice was used to induce ER stress with TM intraperitoneal injection, PPARα and autophagy was upregulated in the mild-ER stress while downregulated in the serious ER stress, measured by qRT-PCR and immunoblotting, further confirmed the finding in vitro. Our results firstly demonstrated that PPARα is a key molecule in the functional conversion of ER stress: protective effects in the mild ER stress was mediated by PPARα-autophagy pathway and destructive effects in the serious ER stress was mediated by PPARα-CHOP pathway.

15.
Biometrics ; 2020 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-32799339

RESUMO

We propose a novel regularized mixture model for clustering matrix-valued data. The proposed method assumes a separable covariance structure for each cluster and imposes a sparsity structure (eg, low rankness, spatial sparsity) for the mean signal of each cluster. We formulate the problem as a finite mixture model of matrix-normal distributions with regularization terms, and then develop an expectation maximization type of algorithm for efficient computation. In theory, we show that the proposed estimators are strongly consistent for various choices of penalty functions. Simulation and two applications on brain signal studies confirm the excellent performance of the proposed method including a better prediction accuracy than the competitors and the scientific interpretability of the solution.

16.
J Zhejiang Univ Sci B ; 21(8): 628-636, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32748578

RESUMO

BACKGROUND: Currently, there are no drugs that have been proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Because of its broad antiviral activity, interferon (IFN) should be evaluated as a potential therapeutic agent for treatment of coronavirus disease 2019 (COVID-19), especially while COVID-19-specific therapies are still under development. METHODS: Confirmed COVID-19 patients hospitalized in the First Affiliated Hospital, School of Medicine, Zhejiang University in Hangzhou, China, from January 19 to February 19, 2020 were enrolled in a retrospective study. The patients were separated into an IFN group and a control group according to whether they received initial IFN-α2b inhalation treatment after admission. Propensity-score matching was used to balance the confounding factors. RESULTS: A total of 104 confirmed COVID-19 patients, 68 in the IFN group and 36 in the control group, were enrolled. Less hypertension (27.9% vs. 55.6%, P=0.006), dyspnea (8.8% vs. 25.0%, P=0.025), or diarrhea (4.4% vs. 19.4%, P=0.030) was observed in the IFN group. Lower levels of albumin and C-reactive protein and higher level of sodium were observed in the IFN group. Glucocorticoid dosage was lower in the IFN group (median, 40 vs. 80 mg/d, P=0.025). Compared to the control group, fewer patients in the IFN group were ventilated (13.2% vs. 33.3%, P=0.015) and admitted to intensive care unit (ICU) (16.2% vs. 44.4%, P=0.002). There were also fewer critical patients in the IFN group (7.4% vs. 25.0%, P=0.017) upon admission. Although complications during admission process were comparable between groups, the discharge rate (85.3% vs. 66.7%, P=0.027) was higher and the hospitalization time (16 vs. 21 d, P=0.015) was shorter in the IFN group. When other confounding factors were not considered, virus shedding time (10 vs. 13 d, P=0.014) was also shorter in the IFN group. However, when the influence of other factors was eliminated using propensity score matching, virus shedding time was not significantly shorter than that of the control group (12 vs. 15 d, P=0.206). CONCLUSIONS: IFN-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Interferon alfa-2/administração & dosagem , Sprays Nasais , Pneumonia Viral/tratamento farmacológico , Eliminação de Partículas Virais/efeitos dos fármacos , Albuminas/análise , Antivirais/administração & dosagem , Betacoronavirus , Proteína C-Reativa/análise , Estudos de Casos e Controles , China , Glucocorticoides/farmacologia , Hospitalização , Humanos , Pandemias , Pontuação de Propensão , Estudos Retrospectivos , Sódio/sangue
17.
J Environ Manage ; 270: 110904, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32721339

RESUMO

An efficient valorization of tea residues into value-added product was developed by Trametes versicolor in solid-state fermentation (SSF). The laccase production of 25.7 U/g dry substrate was obtained by optimizing culture medium and condition, resulting in a 4.0-fold increase compared to that of 6.4 U/g dry substrate under unoptimized condition. During the 7-day cultivation under SSF, 44.7%, 12.2% and 9.8% degradation occurred for lignin, hemicellulose and cellulose in tea residues, respectively. Laccase production reached 31.2 U/g dry substrate by the scaling-up culture in shallow tray system. The dry fermented tea residues were directly used as crude enzyme in the decolorization of malachite green. It possessed a decolorization rate of more than 95% within 120 min and remained 81.3% of decolorization capacity after 6 cycles. The present study provided a useful strategy for low-cost laccase production by SSF and it exhibited great potential for the application in dye decolorization.


Assuntos
Lacase , Trametes , Corantes , Fermentação , Lignina , Chá
18.
Aging (Albany NY) ; 12(14): 13849-13859, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32730223

RESUMO

This retrospective cohort study aimed to investigate the correlation of the neutrophil-to-lymphocyte ratio (NLR) with critical illness in older patients with COVID-19, and evaluate the prognostic power of the NLR at admission. We enrolled 232 patients with COVID-19, aged ≥60 y, in Zhejiang province from January 17 to March 3, 2020. Primary outcomes were evaluated until April 13. Cox regression was performed for prognostic factors. Twenty-nine (12.5%) patients progressed to critical illness. Age, shortness of breath, comorbidities including hypertension, heart disease, and chronic obstructive pulmonary disease, higher NLR, lower albumin levels, and multiple mottling and ground-glass opacity were associated with progression. In the multivariate analysis, older age (hazard ratio [HR] 1.121, confidence interval [CI] 1.070-1.174, P<0.001), heart disease (HR 2.587, CI 1.156-5.787, P=0.021), higher NLR (HR 1.136, CI 1.094-1.180, P < 0.001), and multiple mottling and ground-glass opacity (HR 4.518, CI 1.906-10.712, P<0.001) remained critical illness predictors. The NLR was independently associated with progression to critical illness; the relationship was significant and graded (HR: 1.16 per unit; 95% CI: 1.10-1.22; P for trend < 0.001). Therefore, NLR can be adopted as a prognostic tool to assist healthcare providers predict the clinical outcomes of older patients suffering from COVID-19.


Assuntos
Infecções por Coronavirus/imunologia , Linfócitos , Neutrófilos , Pneumonia Viral/imunologia , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Estudos de Coortes , Infecções por Coronavirus/sangue , Estado Terminal , Progressão da Doença , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Prognóstico , Estudos Retrospectivos , Fatores de Risco
19.
Infect Dis Poverty ; 9(1): 85, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641121

RESUMO

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) is now becoming an enormous threat to public health. The clinical spectrum of COVID-19 is extensive, of which critical cases are with rapid disease progression and high mortality. The aim of our study is to summarize the characteristics of different subtypes and explore risk factors of illness severity for early identification and prompt treatment. METHODS: In this retrospective study, we collected data of patients confirmed COVID-19 in Zhejiang Province from 17 January to 12 February 2020. According to the definition of clinical classification, we divided confirmed cases into four types, and summarize epidemiological and clinical characteristics, laboratory and radiograph findings, treatments, and outcomes, respectively. Moreover, we used univariate and multivariate ordinal logistic regression models to explore risk factors for the severity of illness in patients with COVID-19. RESULTS: A total of 788 patients were enrolled in our study, of whom 52 cases (6.6%) were mild type, 658 cases (83.5%) were common type, 61 cases (7.2%) were severe type, and 17 cases (2.2%) were critical type. Multivariate ordinal logistic regression demonstrated increasing odds of the severity of illness in patients with COVID-19 associated with male (odds ratio [OR] = 1.7, 95% confidence interval [CI]: 1.2-2.6 P = 0.008), fever (OR = 3.6, 95% CI: 2.1-6.3, P <  0.001), cough (OR = 1.7, 95% CI: 1.0-2.9, P = 0.041), hemoptysis (OR = 3.4, 95% CI: 1.1-10.3, P = 0.032), gastrointestinal symptoms (OR = 1.9, 95% CI: 1.0-3.5, P = 0.047), hypertension (OR = 2.6, 95% CI: 1.2-5.6, P = 0.013). With the increase of age-grading, risk for the severity of illness was gradually higher (≤ 18 years [OR = 1.0], 19-40 years [OR = 12.7, 95% CI: 4.5-36.0, P < 0.001], 41-65 years [OR = 14.8, 95% CI: 5.2-42.1, P <  0.001], ≥ 66 years [OR = 56.5, 95% CI: 17.1-186.5, P < 0.001]). CONCLUSIONS: Clinicians should pay close attention to these features in patients with COVID-19 including older age, male, fever, cough, hemoptysis, gastrointestinal symptoms and hypertension to identify the severity of illness as early as possible.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/patologia , Adulto , Distribuição por Idade , Idoso , Betacoronavirus , China/epidemiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
20.
Am J Gastroenterol ; 115(7): 1075-1083, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32618658

RESUMO

INTRODUCTION: Elevated liver enzyme levels are observed in patients with coronavirus disease 2019 (COVID-19); however, these features have not been characterized. METHODS: Hospitalized patients with COVID-19 in Zhejiang Province, China, from January 17 to February 12, 2020, were enrolled. Liver enzyme level elevation was defined as alanine aminotransferase level >35 U/L for men and 25 U/L for women at admission. Patients with normal alanine aminotransferase levels were included in the control group. Reverse transcription polymerase chain reaction was used to confirm severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and patients symptomatic with SARS-CoV-2 infection were defined as patients with COVID-19. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were collected and compared. RESULTS: Of 788 patients with COVID-19, 222 (28.2%) patients had elevated liver enzyme levels (median [interquartile range {IQR}] age, 47.0 [35.0-55.0] years; 40.5% women). Being male, overweight, and smoking increased the risk of liver enzyme level elevation. The liver enzyme level elevation group had lesser pharyngalgia and more diarrhea than the control group. The median time from illness onset to admission was 3 days for liver enzyme level elevation groups (IQR, 2-6), whereas the median hospitalization time for 86 (38.7%) discharged patients was 13 days (IQR, 11-16). No differences in disease severity and clinical outcomes were noted between the groups. DISCUSSION: We found that 28.2% of patients with COVID-19 presented with elevated liver enzyme levels on admission, which could partially be related to SARS-CoV-2 infection. Male patients had a higher risk of liver enzyme level elevation. With early medical intervention, liver enzyme level elevation did not worsen the outcomes of patients with COVID-19.


Assuntos
Infecções por Coronavirus , Hepatite Viral Humana/enzimologia , Testes de Função Hepática , Pandemias , Pneumonia Viral , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Estudos Transversais , Feminino , Hepatite Viral Humana/virologia , Humanos , Hepatopatias/enzimologia , Hepatopatias/virologia , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/complicações , Estudos Retrospectivos , Fatores de Risco
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