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1.
J Proteomics ; : 104207, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33798793

RESUMO

Psoriasis is a chronic skin disorder with undefined pathogenesis. Several biomarkers for this disease have been identified by proteomic analysis. We explored the whole-proteomic changes in 45 pairs of psoriatic and adjacent noninvolved skin tissues in a Chinese population. A total of 3686 proteins were identified, of which 3008 were quantified. A total of 102 and 124 proteins were upregulated and downregulated in lesional skin, respectively. SART1 (P = 3.55 × 10-5) and GLTP (P = 1.54 × 10-3) were the most significantly down- and upregulated proteins. Nearly 90% of these differentially regulated proteins exhibited the same expression trends as those in an online RNA sequencing dataset for psoriasis; 19 differentially regulated proteins exhibited a negative relationship with DNA methylation data for psoriatic lesions. The differentially expressed proteins were enriched in ribosomes, antigen processing and presentation, immune response, and IL-17 signalling pathways. This study identified multiple differentially regulated proteins in psoriatic lesions, which suggested that changes in the proteome play important regulatory roles in psoriasis-associated processes. SIGNIFICANCE: Proteomic analysis was performed in 45 pairs of psoriatic and adjacent noninvolved skin tissues in a Chinese population. More than 3000 proteins were quantified, of which 226 were differentially expressed in psoriatic skin tissues. These proteins were mainly enriched in the immune response, antigen processing and presentation and IL-17 signalling pathways, which have been reported to be associated with the pathogenesis of psoriasis.

2.
JAMA Netw Open ; 4(4): e214846, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33825837

RESUMO

Importance: Atezolizumab plus bevacizumab as a first-line therapy for patients with unresectable or metastatic hepatocellular carcinoma has been shown to improve overall and progression-free survival compared with standard sorafenib treatment. However, because of the high cost of atezolizumab plus bevacizumab, assessment of its value by considering both efficacy and cost is needed. Objective: To evaluate the cost-effectiveness of atezolizumab plus bevacizumab vs sorafenib for patients with unresectable or metastatic hepatocellular carcinoma from a US payer perspective. Design, Setting, and Participants: This economic evaluation was performed from June through September 2020, with a 6-year investment time period. Hypothetical patients were male and female adults 18 years or older who had a diagnosis of locally advanced metastatic or unresectable hepatocellular carcinoma confirmed by histologic or clinical features. Main Outcomes and Measures: Health care costs (adjusted to 2020 US dollars), life-years, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) of atezolizumab plus bevacizumab vs sorafenib were examined using a partitioned survival model. One-way deterministic and probabilistic sensitivity analyses were used to examine model uncertainty. The model was also used to estimate price reductions of atezolizumab plus bevacizumab that would achieve more favorable cost-effectiveness. Results: In the base case analysis of a hypothetical sample of 424 patients, atezolizumab plus bevacizumab was associated with an increase of 0.623 life-years (1.840 vs 1.218 life-years) and 0.484 QALYs (1.412 vs 0.928 QALYs) and with an incremental cost of $156 210 per patient compared with sorafenib. The ICER was $322 500 per QALY (5th to 95th percentile, $149 364-$683 744 per QALY), with 0.6% and 5.1% chance of being cost-effective at willingness-to-pay thresholds of $100 000 and $150 000 per QALY, respectively. The ICER never decreased below $150 000 per QALY in the 1-way sensitivity analyses. To achieve more favorable cost-effectiveness under the thresholds of $150 000 to $100 000 per QALY, the prices of atezolizumab and bevacizumab would need to be reduced by 37% to 47%. Conclusions and Relevance: In this economic evaluation, atezolizumab plus bevacizumab was associated with clinical benefit but was not cost-effective compared with sorafenib for first-line treatment of unresectable or metastatic hepatocellular carcinoma from a US payer perspective. A substantial reduction in price for atezolizumab plus bevacizumab would be needed to achieve favorable cost-effectiveness for this new therapy.

3.
J Pharm Pharmacol ; 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33793788

RESUMO

OBJECTIVES: To assess nuclear protein 1 (NUPR1) level in human gastric cancer (GC) cells, explore the effects of NUPR1 on GC progression, and investigate the possible regulatory mechanism. METHODS: Immunohistochemistry (IHC), Immunoblot and quantitative PCR assays were conducted to detect the NUPR1 level in human GC tissues and corresponding normal tissues. Also, NUPR1 expression level correlates with clinical features of GC patients. 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT), transwell assays, Immunoblot assays, and flow cytometry (FCM) assays were used to evaluate the effects of NUPR1 on the proliferation, invasion, epithelial-mesenchymal transformation (EMT) and apoptosis of GC cells in vitro. Immunoblot assays were performed to detect the potential mechanism in NUPR1-mediated drug resistance. KEY FINDINGS: We found the expression of NUPR1 was upregulated in human gastric cancer tissues and correlated with the clinical features including tumour size, tumour stage and, lymph node metastasis. We further noticed that the depletion of NUPR1 inhibited the invasion and EMT of gastric cancer cells and stimulated the apoptosis. In doxorubicin-resistant gastric cancer cells, yes-associated protein (YAP) activation was up-regulated, and YAP could regulate the expression of NUPR1 to affect drug-resistance. We further provided the evidence that overexpression of NUPR1 reversed the effect of YAP knockdown on cell malignancy and drug resistance via regulating AKT and p21 pathway. CONCLUSIONS: Our findings indicated the involvement of NUPR1 in the progression of gastric cancer and elucidated its molecular mechanism in regulating drug resistance.

4.
Sci Adv ; 7(14)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33789892

RESUMO

Xinjiang is a key region in northwestern China, connecting East and West Eurasian populations and cultures for thousands of years. To understand the genetic history of Xinjiang, we sequenced 237 complete ancient human mitochondrial genomes from the Bronze Age through Historical Era (41 archaeological sites). Overall, the Bronze Age Xinjiang populations show high diversity and regional genetic affinities with Steppe and northeastern Asian populations along with a deep ancient Siberian connection for the Tarim Basin Xiaohe individuals. In the Iron Age, in general, Steppe-related and northeastern Asian admixture intensified, with North and East Xinjiang populations showing more affinity with northeastern Asians and South Xinjiang populations showing more affinity with Central Asians. The genetic structure observed in the Historical Era of Xinjiang is similar to that in the Iron Age, demonstrating genetic continuity since the Iron Age with some additional genetic admixture with populations surrounding the Xinjiang region.

5.
Accid Anal Prev ; 154: 106099, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33770718

RESUMO

There are certain situations that automated driving (AD) systems are still unable to handle, preventing the implementation of Level 5 AD. Thus, a transition of control, colloquially known as take-over of the vehicle, is required when the system sends a take-over request (TOR) upon exiting the operational design domain (ODD). An adaptive TOR along with good take-over performance requires adjusting the time budget (TB) to drivers' visual distraction state, adhering to a reliable visual-distraction-based take-over performance model. Based on a number of driving simulator experiments, the percentage of face orientation to distraction area (PFODA) and time to boundary at take-over timing (TTBT) were proposed to accurately evaluate the degree of visual distraction based on merely face orientation under naturalistic non-driving related tasks (NDRTs) and to evaluate take-over performance, respectively. In order to elucidate the safety boundary, this study also proposed an algorithm to set a suitable minimum value of the TTBT. Finally, a multiple regression model was built to describe the relationship among PFODA, TB and TTBT along with a corrected coefficient of determination of 0.748. Based on the model, this study proposed an adaptive TB adjustment method for the take-over system.

6.
Autophagy ; : 1-2, 2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33779488

RESUMO

ENDOG (endonuclease G), a mitochondrial endonuclease, is known to participate in apoptosis and paternal mitochondria elimination. However, the role and underlying mechanism of ENDOG in regulating macroautophagy remain unclear. We recently reported that ENDOG released from mitochondria promotes autophagy during starvation, which we demonstrated is evolutionarily conserved across species by performing experiments in human cell lines, mice, Drosophila, and C. elegans. This study demonstrates that ENDOG can be phosphorylated by GSK3B, which enhances the interaction between ENDOG with YWHAG and leads to the release of TSC2 and PIK3C3 from YWHAG, followed by MTOR pathway suppression and autophagy initiation. Additionally, the endonuclease activity of ENDOG is essential for activating the DNA damage response and thus inducing autophagy. Consequently, this study uncovered an exciting new role for ENDOG as a crucial regulator of autophagy.

7.
Oncol Rep ; 45(5)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33760175

RESUMO

Hypoxia is a common phenomenon during tumorigenesis and tumour development. In recent years, studies have found that hypoxia­inducible factor (HIF)­2α, also referred to as endothelial PAS domain protein­1, plays an important role in tumours. HIF­2α is an important oncogene and a critical prognostic indicator in non­small cell lung cancer. However, no unified conclusion can be drawn concerning HIF­2α and small cell lung cancer, since few studies to date have focused on their association. An increasing number of studies have confirmed that HIF­2α is involved in tumorigenesis, cell proliferation, angiogenesis, metastasis, drug resistance and radiotherapy failure in lung cancer. Of note, HIF­2α plays a crucial role in lung cancer to maintain cancer cell stemness. Based on the importance of HIF­2α in lung cancer, HIF­2α­targeted therapy has been attracting increasing attention. Although this strategy currently appears to be promising in vitro, it has never been assessed as a therapy for lung cancer. The aim of the present review was to summarize the contribution of HIF­2α to various aspects of lung cancer, as well as its potential as targeted therapy.

8.
Opt Express ; 29(3): 3327-3341, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33770933

RESUMO

The optical properties of microlens arrays may be significantly affected by the optical crosstalk effect between adjacent lenses. Recently, this issue has triggered increasing attention in the scientific community. In this study, an integrated microlens array (MLA) consisting of self-aligning convergent waveguides of microlenses was fabricated. The optical crosstalk effect does not influence the performance of such system. Based on the self-focusing effect principle, self-writing of the waveguide array was achieved in a photosensitive polymer. The light collection and guiding performance of the MLA with and without thermal cross-linking treatment was analyzed in depth. The relation between the stray light and the filling rate of the MLA shows that a high filling rate decreases the optical crosstalk. Finally, an integrated MLA with a large area, high uniformity, and excellent optical performance was fabricated.

9.
Virol Sin ; 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33723807

RESUMO

Raising a heterologous tier 2 neutralizing antibody (nAb) response remains a daunting task for HIV vaccine development. In this study, we explored the utility of diverse HIV-1 envelope (Env) immunogens in a sequential immunization scheme as a solution to this task. This exploration stemmed from the rationale that gp145, a membrane-bound truncation form of HIV Env, may facilitate the focusing of induced antibody response on neutralizing epitopes when sequentially combined with the soluble gp140 form as immunogens in a prime-boost mode. We first showed that gp140 DNA prime-gp145 Tiantan vaccinia (TV) boost likely represents a general format for inducing potent nAb response in mice. However, when examined in rhesus macaque, this modality showed little effectiveness. To improve the efficacy, we extended the original modality by adding a strong protein boost, namely native-like SOSIP.664 trimer displayed on ferritin-based nanoparticle (NP), which was generated by a newly developed click approach. The resulting three-immunization regimen succeeded in eliciting tier-2 nAb response with substantial breadth when implemented in rhesus macaque over a short 8-week schedule. Importantly, the elicited nAb response was able to effectively contain viremia upon a heterologous SHIV challenge. Collectively, our studies highlighted that diversification of Env immunogens, in both types and formulations, under the framework of a sequential immunization scheme might open new opportunity toward HIV vaccine development.

10.
J Hazard Mater ; 415: 125649, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33743377

RESUMO

HCHO is the most concerned indoor air pollutant that photocatalytic degradation is a feasible approach. To achieve efficient and complete degradation of HCHO under visible light irradiation, heteroatoms are usually doped in TiO2. But using natural materials as a dopant instead of expensive and toxic chemicals to fertilize TiO2 remains challenging. This paper proposes a sustainable and green approach to synthesize an efficient N, Ca co-doped TiO2 photocatalyst (TIMP) by using the insoluble matrix proteins (IMPs) extracted from abalone shell. TIMP-0.8 achieves near completely degradation HCHO within 45 min under visible light at ambient temperature and exhibits superior stability after 7 cycles. TIMP-0.8 has monodispersity with smaller diameter, high porosity, abundant defects and high adsorption affinity for surface hydroxyls compared with pure TiO2. With the assistance of IMPs, the rate-determining step of HCHO degradation changes from -COOH oxidation to spontaneous decomposition of HCO3-, significantly facilitating the elimination and mineralization of HCHO. Overall, IMPs from abalone shell are natural surfactant, bio-templet, and dopant for TiO2 modification, contributing to desirable visible-light photocatalytic performance for HCHO degradation. This paper provides new insight for high-value utilization of waste shell and photocatalytic indoor purification.

11.
J Am Chem Soc ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33724014

RESUMO

The bottom-up assembly of periodically ordered structures provides a scalable way for producing metastructured materials with exotic optical and mechanical properties. However, direct self-assembly of small molecules into such metastructures beyond the nanoscale remains an unresolved issue. Here we demonstrate that metastructured assemblies of two-dimensional (2D) polymers, specifically 2D covalent organic frameworks (COFs), can be directly synthesized in solution. We applied 2D COF monomer polycondensation to prepare flower-shaped particles consisting of highly crystalline "petals" with sizes larger than 20 µm. The petal comprises periodically arranged COF nanoflake units with tunable lengths of 490-850 nm, thicknesses about 20 nm, interflake spacing around 14 nm, and Hermans orientation factors up to 0.998. Such a metastructure is mechanically robust and remains almost intact even after full pyrolysis at 900 °C. It also demonstrates unique birefringence and polarization-dependent resonances under visible-near-infrared light not observed in its constituents, 2D COF polycrystals, and with well-defined nanopores of 1.8 nm and the high surface area of 1576 m2/g. Such metastructured particles with nanopores are well-suited as novel particulate optical devices for collecting and storing information about their surroundings that can be easily read out by polarization imaging with high sensitivity, as demonstrated by their explosive detection and anticounterfeiting applications. Self-assembly of 2D polymers into metastructures may become an important method for developing functional materials with unprecedented properties and extensive applications.

12.
J Clin Nurs ; 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33656210

RESUMO

AIMS AND OBJECTIVES: To determine the health-related quality of life (HRQoL) of COVID-19 patients after discharge and its predicting factors. BACKGROUND: COVID-19 has caused a worldwide pandemic and led a huge impact on the health of human and daily life. It has been demonstrated that physical and psychological conditions of hospitalised COVID-19 patients are impaired, but the studies focus on physical and psychological conditions of COVID-19 patients after discharge from hospital are rare. DESIGN: A multicentre follow-up study. METHODS: This was a multicentre follow-up study of COVID-19 patients who had discharged from six designated hospitals. Physical symptoms and HRQoL were surveyed at first follow-up (the third month after discharge). The latest multiple laboratory findings were collected through medical examination records. This study was performed and reported in accordance with STROBE checklist. RESULTS: Three hundred eleven patients (57.6%) were reported with one or more physical symptoms. The scores of HRQoL of COVID-19 patients at third month after discharge, except for the dimension of general health, were significantly lower than Chinese population norm (p < .001). Results of logistic regression showed that female (odds ratio (OR): 1.79, 95% confidence interval (CI): 1.04-3.06), older age (≥60 years) (OR: 2.44, 95% CI: 1.33-4.47) and the physical symptom after discharge (OR: 40.15, 95% CI: 9.68-166.49) were risk factors for poor physical component summary; the physical symptom after discharge (OR: 6.68, 95% CI: 4.21-10.59) was a risk factor for poor mental component summary. CONCLUSIONS: Health-related quality of life of discharged COVID-19 patients did not come back to normal at third month after discharge and affected by age, sex and the physical symptom after discharge. RELEVANCE TO CLINICAL PRACTICE: Healthcare workers should pay more attention to the physical and psychological rehabilitation of discharged COVID-19 patients. Long-term follow-up on COVID-19 patients after discharge is needed to determine the long-term impact of COVID-19.

13.
Water Res ; 194: 116915, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33607387

RESUMO

In this study, visible light (VL) was adopted for permanganate (PM) activation without additional catalyst, where sulfamethazine (SMT) was selected as the probe compound. Experiment results showed that the VL/PM system can effectively degrade SMT through pseudo-first-order reaction kinetics. Influencing factors including PM dosage, solution pH, humid acid (HA) and coexisting anions (CO32-, SO42-, Cl- and NO3-) which affect SMT photo-degradation were also examined. Pyrophosphate (PP) had an inhibitory effect on SMT degradation due to the complexation of PP with Mn (III). Electron spin resonance (ESR) spectrometry and UV-Vis spectrophotometer proved that VL can activate PM to generate ·O2- and Mn (III) reactive species. Furthermore, based on the active site prediction, intermediates identification and Density Functional Theory (DFT) calculation, two main degradation pathways involving SMT molecular rearrangement and cleavage of S-N bond were proposed. Moreover, the energy barriers of the two degradation pathways were also calculated. This study offers a novel approach for aqueous SMT removal and deepens our understanding of the degradation mechanism of SMT through DFT calculation, which hopes to shed light on the future development of VL/PM treatment.


Assuntos
Sulfametazina , Poluentes Químicos da Água , Peróxido de Hidrogênio , Luz , Compostos de Manganês , Óxidos
14.
J Cell Mol Med ; 25(6): 2931-2943, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33523568

RESUMO

Increased adenosine helps limit infarct size in ischaemia/reperfusion-injured hearts. In cardiomyocytes, 90% of adenosine is catalysed by adenosine kinase (ADK) and ADK inhibition leads to higher concentrations of both intracellular adenosine and extracellular adenosine. However, the role of ADK inhibition in myocardial ischaemia/reperfusion (I/R) injury remains less obvious. We explored the role of ADK inhibition in myocardial I/R injury using mouse left anterior ligation model. To inhibit ADK, the inhibitor ABT-702 was intraperitoneally injected or AAV9 (adeno-associated virus)-ADK-shRNA was introduced via tail vein injection. H9c2 cells were exposed to hypoxia/reoxygenation (H/R) to elucidate the underlying mechanisms. ADK was transiently increased after myocardial I/R injury. Pharmacological or genetic ADK inhibition reduced infarct size, improved cardiac function and prevented cell apoptosis and necroptosis in I/R-injured mouse hearts. In vitro, ADK inhibition also prevented cell apoptosis and cell necroptosis in H/R-treated H9c2 cells. Cleaved caspase-9, cleaved caspase-8, cleaved caspase-3, MLKL and the phosphorylation of MLKL and CaMKII were decreased by ADK inhibition in reperfusion-injured cardiomyocytes. X-linked inhibitor of apoptosis protein (XIAP), which is phosphorylated and stabilized via the adenosine receptors A2B and A1/Akt pathways, should play a central role in the effects of ADK inhibition on cell apoptosis and necroptosis. These data suggest that ADK plays an important role in myocardial I/R injury by regulating cell apoptosis and necroptosis.

15.
BMJ Open ; 11(2): e040563, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33550233

RESUMO

OBJECTIVE: The objective of this retrospective cohort study was to explore the optimal range of the total progressive motile sperm count (TPMSC) for live birth in couples with varying infertility diagnosis undergoing intrauterine insemination (IUI) in a university-affiliated teaching hospital. METHODS: A total of 2647 couples and 5171 IUI cycles were included between January 2015 and December 2018. Of those, 1542 cycles were performed due to unexplained infertility, 1228 cycles due to anovulation, 1120 cycles due to mild male factor infertility and 122 cycles due to mild endometriosis. The primary outcome measure was live birth rate (LBR). The secondary outcome measure was clinical pregnancy rate (CPR). RESULTS: The CPR and LBR were highest in patients with a diagnosis of anovulation compared with the other three groups of patients. The CPR and LBR in patients with unexplained, mild male factor and mild endometriosis were comparable. For the patients with mild male factor infertility, the CPR with prewash TPMSC of >75.0 M and postwash TPMSC of 65.10 M was above 10%, statistically significantly higher than other quartiles of TPMSC (p<0.05). The LBR with postwash TPMSC of >65.10 M was statistically significantly higher than other groups (p<0.05). However, in patients with unexplained infertility, the CPR and LBR were not statistically different in quartiles of TPMSC, being less than 10%. Overall, there was only one clinical pregnancy and no live birth in patients >40 years of age. CONCLUSIONS: In conclusion, the infertility diagnosis plays a significant role for the patient undergoing IUI. Thus, the anovulatory patients benefitted most from IUI, irrespective of TPMSC. For patients with unexplained infertility, TPMSC does not affect the success rate of IUI. Overall,female patients more than 40 years old should not be referred to IUI.

16.
BMC Pulm Med ; 21(1): 64, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33627118

RESUMO

OBJECTIVES: We aimed to identify high-risk factors for disease progression and fatality for coronavirus disease 2019 (COVID-19) patients. METHODS: We enrolled 2433 COVID-19 patients and used LASSO regression and multivariable cause-specific Cox proportional hazard models to identify the risk factors for disease progression and fatality. RESULTS: The median time for progression from mild-to-moderate, moderate-to-severe, severe-to-critical, and critical-to-death were 3.0 (interquartile range: 1.8-5.5), 3.0 (1.0-7.0), 3.0 (1.0-8.0), and 6.5 (4.0-16.3) days, respectively. Among 1,758 mild or moderate patients at admission, 474 (27.0%) progressed to a severe or critical stage. Age above 60 years, elevated levels of blood glucose, respiratory rate, fever, chest tightness, c-reaction protein, lactate dehydrogenase, direct bilirubin, and low albumin and lymphocyte count were significant risk factors for progression. Of 675 severe or critical patients at admission, 41 (6.1%) died. Age above 74 years, elevated levels of blood glucose, fibrinogen and creatine kinase-MB, and low plateleta count were significant risk factors for fatality. Patients with elevated blood glucose level were 58% more likely to progress and 3.22 times more likely to die of COVID-19. CONCLUSIONS: Older age, elevated glucose level, and clinical indicators related to systemic inflammatory responses and multiple organ failures, predict both the disease progression and the fatality of COVID-19 patients.


Assuntos
Glicemia/metabolismo , /mortalidade , Progressão da Doença , Hiperglicemia/sangue , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Bilirrubina/sangue , Proteína C-Reativa/metabolismo , China/epidemiologia , Estado Terminal , Feminino , Febre/virologia , Humanos , Hiperglicemia/complicações , L-Lactato Desidrogenase/sangue , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Albumina Sérica/metabolismo , Fatores de Tempo
17.
Sci Rep ; 11(1): 4145, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33603047

RESUMO

The pandemic of Coronavirus Disease 2019 (COVID-19) is causing enormous loss of life globally. Prompt case identification is critical. The reference method is the real-time reverse transcription PCR (RT-PCR) assay, whose limitations may curb its prompt large-scale application. COVID-19 manifests with chest computed tomography (CT) abnormalities, some even before the onset of symptoms. We tested the hypothesis that the application of deep learning (DL) to 3D CT images could help identify COVID-19 infections. Using data from 920 COVID-19 and 1,073 non-COVID-19 pneumonia patients, we developed a modified DenseNet-264 model, COVIDNet, to classify CT images to either class. When tested on an independent set of 233 COVID-19 and 289 non-COVID-19 pneumonia patients, COVIDNet achieved an accuracy rate of 94.3% and an area under the curve of 0.98. As of March 23, 2020, the COVIDNet system had been used 11,966 times with a sensitivity of 91.12% and a specificity of 88.50% in six hospitals with PCR confirmation. Application of DL to CT images may improve both efficiency and capacity of case detection and long-term surveillance.


Assuntos
/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , /epidemiologia , China/epidemiologia , Confiabilidade dos Dados , Aprendizado Profundo , Humanos , Pulmão/patologia , Pneumonia/diagnóstico por imagem , Estudos Retrospectivos , Sensibilidade e Especificidade
18.
Mol Cancer Ther ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33632873

RESUMO

Docetaxel (DTX) and cabazitaxel (CBZ) are guideline-chemotherapy treatments for metastatic castration-resistant prostate cancer (mCRPC), which comprises the majority of prostate cancer (PCa) deaths. TNF-related apoptosis inducing ligand (TRAIL) is an anti-cancer agent that is selectively cytotoxic to cancer cells; however, many human cancers are resistant to TRAIL. In this study, we sensitized androgen-independent and TRAIL-resistant PCa cells to TRAIL-mediated apoptosis via taxane therapy and examined the mechanism of sensitization. DU145 and PC3 cells displayed no significant reduction in cell viability when treated with soluble TRAIL, DTX, or CBZ alone indicating that both cell lines are resistant to TRAIL and taxanes individually. Taxane and TRAIL combination synergistically amplified apoptosis strongly suggesting that taxanes sensitize prostate cancer cells to TRAIL. A Jun N-terminal kinases (JNK) inhibitor inhibited apoptosis in treated cells and significantly reduced death receptor expression indicating JNK activation by ER stress sensitizes PCa cells to TRAIL-induced apoptosis by upregulating DR4/DR5 expression. In addition, suppression of C/EBP homologous protein (CHOP) reduced TRAIL sensitization in both cell lines indicating that ER stress-related apoptosis is mediated, in part by CHOP. Cytochrome c knockdown showed a significant decrease in sensitivity in PC3 cells, but not in Bax-deficient DU145 cells. A computational model was used to simulate apoptosis for cells treated with taxane and TRAIL therapy as demonstrated in in vitro experiments. Pretreatment with taxanes sensitized cells to apoptosis induced by TRAIL-mediated apoptosis, demonstrating that combining TRAIL with ER stress inducers is a promising therapy to reverse TRAIL resistance to treat mCRPC.

19.
Adv Healthc Mater ; : e2002038, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33586335

RESUMO

The strategies of combining photodynamic therapy (PDT) with other therapeutics are considered to be the most suitable methods in improving the antitumor therapeutic efficiency. Herein, a "Linkage Mechanism" strategy based on thermal controllable multishell nanoparticles (CuS@SiO2 -l-Arg (l-arginine)@PCM (phase-change material)-Ce6 (chiorin e6)) is proposed for combing PDT and NO-based gas therapy. Upon 1060 nm laser irradiation, the PCMs will melt under the photothermal effect induced by CuS and the loaded Ce6 and l-Arg can accurately release from the nanoparticles. Under further 660 nm laser irradiation, the released Ce6 will produce plenty of singlet oxygen (1 O2 ) for PDT, while the generated 1 O2 can oxidize l-Arg to release NO for the synergy of PDT and gas therapy. The "Linkage Mechanism" can achieve precise release of the payloads under the control of photothermal effect at tumor site, and the chain reaction of PDT and gas therapy overcomes the problem of premature release of gas during transportation. Benefiting from the guidance of fluorescence imaging and second near infrared photoacoustic imaging by Ce6 and CuS, both in vitro and in vivo experiments present effective antitumor efficiencies. The nanoparticles provide new ideas for controllable release of drugs and the synergistic effect of multiple treatments, possessing great application prospects.

20.
Biomed Res Int ; 2021: 6656926, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33542922

RESUMO

Backgrounds: Intra-aortic balloon counterpulsation is increasingly used in acute myocardial infarction complicated by cardiogenic shock. The aim of this study was to explore the preference, effect, and prognosis of intra-aortic balloon counterpulsation in acute myocardial infarction complicated by cardiogenic shock patients. Methods: Data of acute myocardial infarction complicated by cardiogenic shock patients at the Fourth Medical Center of PLA General Hospital were collected retrospectively. A propensity score was calculated with a logistic regression which contained clinically meaningful variables and variables selected by Lasso and then used to match the control group. The cumulative incidence curve and Gray's test were employed to analyse the effect and prognosis of intra-aortic balloon counterpulsation on mortality. Results: A total of 1962 acute myocardial infarction cases admitted between May 2015 and November 2018 were identified, and 223 cases with acute myocardial infarction complicated by cardiogenic shock were included as the study cohort, which contained 34 cases that received IABP and 189 cases that did not receive IABP. Patients with higher alanine aminotransferase (OR = 1.93, 95% CI 1.29-2.98), higher triglyceride (OR = 3.71, 95% CI 1.87-7.95), and higher blood glucose (OR = 1.08, 95% CI 0.99-1.18) had a higher probability of receiving intra-aortic balloon counterpulsation. In the propensity score matching analysis, 34 cases received intra-aortic balloon counterpulsation and 102 matched controls were included in the comparison. By comparing the cumulative incidence of in-hospital mortality, there was no statistically significant difference between the intra-aortic balloon counterpulsation group and matched control group (P = 0.454). Conclusion: The use of intra-aortic balloon counterpulsation may not improve the prognosis of the acute myocardial infarction complicated by cardiogenic shock patients.

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