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1.
Int J Radiat Oncol Biol Phys ; 119(4): 1222-1233, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38266782

RESUMO

PURPOSE: Radioresistance of lung cancer poses a significant challenge when it comes to the treatment of advanced, recurrent, and metastatic cases. Ovarian tumor domain ubiquitin aldehyde binding 1 (OTUB1) is a key member of the deubiquitinase OTU superfamily. This protein is involved in various cellular functions, including cell proliferation, iron death, lipid metabolism, and cytokine secretion as well as immune response processes. However, its specific role and molecular mechanism in lung cancer radioresistance remain to be clarified. METHODS AND MATERIALS: The expression levels of OTUB1 in paired lung cancer tissues were determined by immunohistochemistry. In vitro and in vivo experiments were conducted to investigate the impact of OTUB1 on the growth and proliferation of lung cancer. Coimmunoprecipitation and Western blotting techniques were performed to examine the interaction between OTUB1 and CHK1. The DNA damage response was measured by comet tailing and immunofluorescence staining. KEGG pathways and Gene Ontology terms were analyzed based on RNA sequencing. RESULTS: Our findings reveal a high frequency of OTUB1 overexpression, which is associated with an unfavorable prognosis in patients with lung cancer. Through comprehensive investigations, we demonstrate that OTUB1 depletion impairs the process of DNA damage repair and overcomes radioresistance. In terms of the underlying mechanism, our study uncovers that OTUB1 deubiquitinates and stabilizes CHK1, which enhances CHK1 stability, thereby regulating DNA damage and repair. Additionally, we identify CHK1 as the primary downstream effector responsible for mediating the functional effects exerted by OTUB1 specifically in lung cancer. Importantly, OTUB1 has the potential to be a valuable marker for improving the efficacy of radiation therapy for lung adenocarcinoma. CONCLUSIONS: These findings unveil a novel role for OTUB1 in enhancing radioresistance by deubiquitination and stabilization of the expression of CHK1 in lung cancer and indicate that targeting OTUB1 holds great potential as an effective therapeutic approach for enhancing the efficacy of radiation therapy in lung cancer.


Assuntos
Quinase 1 do Ponto de Checagem , Progressão da Doença , Neoplasias Pulmonares , Tolerância a Radiação , Ubiquitinação , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Quinase 1 do Ponto de Checagem/metabolismo , Humanos , Animais , Linhagem Celular Tumoral , Camundongos , Proliferação de Células , Reparo do DNA , Cisteína Endopeptidases/metabolismo , Dano ao DNA , Proteases Específicas de Ubiquitina/metabolismo , Feminino , Camundongos Nus , Enzimas Desubiquitinantes/metabolismo , Estabilidade Proteica
2.
Angiology ; 75(4): 375-385, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36809177

RESUMO

Whether percutaneous coronary intervention for chronic total occlusion (CTO-PCI) in diabetic patients offers more benefits compared with initial medical therapy (CTO-MT) is unclear. In this study, diabetic patients with one CTO (clinical manifestations: stable angina or silent ischemia) were enrolled. Consecutively, enrolled patients (n = 1605) were assigned to different groups: CTO-PCI (1044 [65.0%]) and initial CTO-MT (561 [35%]). After a median follow-up of 44 months, CTO-PCI tended to be superior to initial CTO-MT in major adverse cardiovascular events (adjusted hazard-ratio [aHR]: .81, 95% conference-interval: .65-1.02) and significantly superior in cardiac death (aHR: .58 [.39-.87]) and all-cause death (aHR: .678[.473-.970]). Such superiority mainly attributed to a successful CTO-PCI. CTO-PCI tended to be performed in patients with younger age, good collaterals, left anterior descending branch CTO, and right coronary artery CTO. While, those with left circumflex CTO and severe clinical/angiographic situations were more likely to be assigned to initial CTO-MT. However, none of these variables influenced the benefits of CTO-PCI. Thus, we concluded that for diabetic patients with stable CTO, CTO-PCI (mainly successful CTO-PCI) offered patients survival benefits over initial CTO-MT. These benefits were consistent regardless of clinical/angiographic characteristics.


Assuntos
Oclusão Coronária , Diabetes Mellitus , Intervenção Coronária Percutânea , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Oclusão Coronária/complicações , Oclusão Coronária/terapia , Vasos Coronários , Doença Crônica , Resultado do Tratamento , Fatores de Risco , Angiografia Coronária , Sistema de Registros
3.
Med Phys ; 51(3): 1763-1774, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37690455

RESUMO

BACKGROUND: Globally, stroke is the third most significant cause of disability. A stroke may produce motor, sensory, perceptual, or cognitive disorders that result in disability and affect the likelihood of recovery, affecting a person's ability to function. Evaluation post-stroke is critical for optimal stroke care. PURPOSE: Traditional methods for classifying the clinical disorders of cognitive and motor in stroke patients use assessment and interrogative measures, which are time-consuming, complex, and labor-intensive. In response to the current situation, this study develops an algorithm to automatically classify motor and cognitive disorders in stroke patients by 3D brain MRI to assist physicians in diagnosis. METHODS: First, radiomics and fusion features are extracted from the OAx T2 Propeller of 3D brain MRI. Then, we use 14 machine learning models and one model ensemble method to predict Fugl-Meyer and MMSE levels of stroke patients. Next, we evaluate the models using accuracy, recall, f1-score, and area under the curve (AUC). Finally, we employ SHAP to explain the output of the model. RESULTS: The best predictive models come from Random Forest (RF) Classifier with fusion features in cognitive classification and Linear Discriminant Analysis (LDA) with radiomics features in motor classification. The highest accuracies are 92.0 and 82.5% for cognitive and motor disorders. CONCLUSIONS: MRI brain maps can classify the cognitive and motor disorders of stroke patients. Radiomics features demonstrate its merits. The proposed algorithms with MRI images can efficiently assist physicians in diagnosing the cognitive and motor disorders of stroke patients in clinical practice. Additionally, this lessens labor costs, improves diagnostic effectiveness, and avoids the subjective difference that comes with manual assessment.


Assuntos
Transtornos Motores , Acidente Vascular Cerebral , Humanos , Transtornos Motores/diagnóstico por imagem , Transtornos Motores/etiologia , Imageamento por Ressonância Magnética , Neuroimagem , Aprendizado de Máquina , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Cognição
4.
Front Microbiol ; 14: 1301744, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38107851

RESUMO

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most commonly encountered pathogens among burn patients incurring substantial morbidity and mortality. To investigate the epidemiology and features of MRSA in burn wound infections, we conducted a 10-year retrospective study on MRSA isolated from burn patients with burn wound infections from southeast China from 2013 to 2022. Methods: One hundred MRSA isolates (10 isolates each year) from burn wound infection among burn patients from 2013 to 2022 were randomly selected and enrolled. In addition to the clinical data of the 100 burn patients, MRSA isolates were characterized by antimicrobial susceptibility testing, detection of toxin genes, and molecular typing. Results: The median time from the onset of burns and admission to MRSA detected was 13 and 5 days, respectively. No MRSA isolate was found resistant to quinupristin/dalfopristin, linezolid, and vancomycin. Toxin gene seg was found most frequently (90%) followed by sea (70%) and eta (64%). CC8 (74%), ST239 (70%), and SCCmec III (72%) were the most common CC, ST, and SCCmec types, respectively. Conclusion: ST239-III (70%) was the predominant clone found in MRSA from burn wound infection among burn patients in southeast China. ST239-III was less found from 2018 to 2022. A higher diversity of MRSA clones was observed in these recent 5 years than that from 2013 to 2017.

5.
Antimicrob Resist Infect Control ; 12(1): 118, 2023 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-37898771

RESUMO

BACKGROUND: With the widespread spread of carbapenem-resistant gram-negative bacteria (CR-GNB) in medical facilities, the carriage of CR-GNB among critically ill patients has become a significant concern in intensive care units (ICU). This study aimed to develop a scoring system to identify CR-GNB carriers upon ICU admission. METHODS: Consecutive critically ill patients admitted to the ICU of Shanghai Ruijin Hospital between January 2017 and December 2020 were included. The patients were then divided into training and testing datasets at a 7:3 ratio. Parameters associated with CR-GNB carriage were identified using least absolute shrinkage and selection operator regression analysis. Each parameter was assigned a numerical score ranging from 0 to 100 using logistic regression analysis. Subsequently, a four-tier risk-level system was developed based on the cumulative scores, and assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: Of the 1736 patients included in this study, the prevalence of CR-GNB carriage was 10.60%. The clinical scoring system including seven variables (neurological disease, high-risk department history, length of stay ≥ 14 days, ICU history, invasive mechanical ventilation, gastrointestinal tube placement, and carbapenem usage) exhibited promising predictive capabilities. Patients were then stratified using the scoring system, resulting in CR-GNB carriage rates of 2.4%, 12.0%, 36.1%, and 57.9% at the respective risk levels (P < 0.001). Furthermore, the AUC of the developed model in the training set was calculated to be 0.82 (95% CI, 0.78-0.86), while internal validation yielded an AUC of 0.83 (95% CI, 0.77-0.89). CONCLUSIONS: The ICU-CARB Score serves as a straightforward and precise tool that enables prompt evaluation of the risk of CR-GNB carriage at the time of ICU admission, thereby facilitating the timely implementation of targeted pre-emptive isolation.


Assuntos
Antibacterianos , Carbapenêmicos , Humanos , Carbapenêmicos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Estado Terminal , China/epidemiologia , Bactérias Gram-Negativas , Unidades de Terapia Intensiva
6.
J Cancer Res Clin Oncol ; 149(16): 15039-15053, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37612389

RESUMO

OBJECTIVE: Metastasis of lung cancer is an important factor affecting survival. The present study proposed to establish and verify a nomogram for predicting overall survival (OS) in lung adenocarcinoma (LUAD) patients with different patterns of metastasis. METHODS: A total of 9727 patients diagnosed with metastatic LUAD patients from 2010 to 2015 were enrolled based on surveillance, epidemiology and end results (SEER) Database and then randomly divided into training and validation cohorts, and 136 patients in our Cancer Center were enrolled as the external validation cohort. Univariate and multivariate analyses were performed to evaluate the prognostic impact on OS. A prognostic nomogram was constructed and evaluated by C-index, calibration curve, decision curve analysis (DCA), and risk stratification system. RESULTS: Ultimately, 6809 and 2918 patients diagnosed with metastatic LUAD in the training and validation cohorts were enrolled in the study, respectively. A male sex, a later T and N stage, a larger tumor size, treatment including no surgery, no chemotherapy and no radiotherapy, metastasis sites were found to be independent risk factors in LUAD patients for worse OS, and then incorporated into the nomogram. The frequency of bone metastasis was the highest, and in single site metastasis, the prognosis of liver metastasis was the worst. Two-site metastasis is more common than three-site and four-site metastasis, and co-metastasis eventually leads to a worse survival outcome. The C-index value of nomogram for predicting OS were 0.798, 0.703 and 0.698 in the internal training, validation and external validation cohorts, separately. The calibration curves for the 6-months, 1-year and 2-year showed significant agreement between nomogram models and actual observations. The DCA curves indicated nomogram was more beneficial than the AJCC TNM stage. Patients were further divided into low-risk and high-risk groups according to nomogram predicted scores and developed a survival risk classification system. CONCLUSIONS: Our prognostic nomogram is expected to be an accurate and individualized clinical predictive tool for predicting OS in LUAD patients with different patterns of metastasis.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Masculino , Prognóstico , Nomogramas , Calibragem
7.
Sensors (Basel) ; 23(10)2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37430598

RESUMO

Spatial structured light (SL) can achieve three-dimensional measurements with a single shot. As an important branch in the field of dynamic reconstruction, its accuracy, robustness, and density are of vital importance. Currently, there is a wide performance gap of spatial SL between dense reconstruction (but less accurate, e.g., speckle-based SL) and accurate reconstruction (but often sparser, e.g., shape-coded SL). The central problem lies in the coding strategy and the designed coding features. This paper aims to improve the density and quantity of reconstructed point clouds by spatial SL whilst also maintaining a high accuracy. Firstly, a new pseudo-2D pattern generation strategy was developed, which can improve the coding capacity of shape-coded SL greatly. Then, to extract the dense feature points robustly and accurately, an end-to-end corner detection method based on deep learning was developed. Finally, the pseudo-2D pattern was decoded with the aid of the epipolar constraint. Experimental results validated the effectiveness of the proposed system.

8.
Chem Biodivers ; 20(7): e202300589, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37254228

RESUMO

The chemical investigation of the rarely studied soft coral Sinularia tumulosa resulted in the discovery of five oxygenated cembrane diterpenes 1-5, including two new compounds situmulins A (1) and B (2). The structures of 1 and 2 were established through the extensive analyses of 1D and 2D NMR spectral data together with the comparisons with the known compounds. Furthermore, the absolute configuration of 1 was determined by the time-dependent density functional theory (TDDFT) ECD approach, while the relative configuration of 2 was assigned via the quantum mechanical-NMR (QM-NMR) calculations. It might be worth to point out it is the first time to disclose the presence of cembrane diterpenes in the title species. In the bioassays, compound 2 not only showed strong antibacterial activities against fish pathogenic bacteria Streptococcus parauberis FP KSP28 and Phoyobacterium damselae FP2244 with both minimum inhibitory concentration for 90 % (MIC90 ) values of 25 µM, but also demonstrated substantial inhibitory efficacy against vancomycin-resistant Enterococcus faecium bacteria G1, G4, G7, G8 and G13 from several individuals, with MIC90 values of 25, 50, 100, 50 and 25 µM, respectively.


Assuntos
Antozoários , Diterpenos , Animais , Antozoários/química , Espectroscopia de Ressonância Magnética/métodos , Diterpenos/farmacologia , Diterpenos/química , China , Estrutura Molecular
9.
Res Comp Int Educ ; 18(2): 186-205, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38603449

RESUMO

This paper draws attention to the current and possible effects of COVID-19 on the mobility trajectories of mainland Chinese students studying in Asia. By drawing on 35 biographical interviews, this paper focuses on their decision to study in Asian countries and regions. Particularly, it calls for more attention to Asia in global student mobilities and discusses whether COVID-19 has changed the position of Asia in the global landscape of student mobility. Results show that even if COVID-19 provides an opportunity for Asian universities to embrace more international students, Asia still lacks the capability to attract great numbers of them. Finally, the study argues that college students' choice of mobility destinations is shaped by their perception of the central-periphery structure of higher education, which is hard to be shaken by the pandemic.

10.
Am J Transl Res ; 14(10): 7172-7177, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36398233

RESUMO

PURPOSE: After extracting impacted mandibular third molars (IMM3), the resulting bone loss at the distal surface of the distal root of mandibular second molars (MM2) is responsible for the poor stability of MM2. This study aimed to identify the clinical osteogenesis effect of recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded calcium phosphate cements (CPCs) and rhBMP-2 delivery systems (rhBMP-2/CPCs, named CPCII) on bone loss repair at the distal surface of the MM2 distal root after IMM3 extraction. METHODS: Written informed consent was obtained from every participant whose IMM3 needed extraction. The impact of IMM3 on both sides was basically identical. From April 2014 to March 2016, extraction of IMM3 was performed in 9 patients (5 males/4 females, 26-42 years old). One side was randomly selected as the experimental group, and CPCII systems were implanted into the distal surface of the distal root in dental extraction sockets. The wounds on the other side were sutured and allowed to heal naturally (be treated as the control group). New bone formation in the alveolar fossa was detected 3 and 12 months after the operation by cone-beam computed tomography (CBCT) to measure the distance from the cementoenamel junction (CEJ) to the crest of the alveolar ridge (CAR). RESULTS: The CAR-CEJ distance on the test side was less than that on the control side (P<0.5). CONCLUSION: The quantity of new bone formation in the experimental group was greater than that in the control group. CPCII systems have osteogenic potential in the healing process of tooth extraction sockets.

11.
Front Cell Dev Biol ; 10: 769711, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35211471

RESUMO

Lung adenocarcinoma (LUAD) is a frequently diagnosed cancer type, and many patients have already reached an advanced stage when diagnosed. Thus, it is crucial to develop a novel and efficient approach to diagnose and classify lung adenocarcinoma at an early stage. In our study, we combined in silico analysis and machine learning to develop a new five-gene-based diagnosis strategy, which was further verified in independent cohorts and in vitro experiments. Considering the heterogeneity in cancer, we used the MATH (mutant-allele tumor heterogeneity) algorithm to divide patients with early-stage LUAD into two groups (C1 and C2). Specifically, patients in C2 had lower intratumor heterogeneity and higher abundance of immune cells (including B cell, CD4 T cell, CD8 T cell, macrophage, dendritic cell, and neutrophil). In addition, patients in C2 had a higher likelihood of immunotherapy response and overall survival advantage than patients in C1. Combined drug sensitivity analysis (CTRP/PRISM/CMap/GDSC) revealed that BI-2536 might serve as a new therapeutic compound for patients in C1. In order to realize the application value of our study, we constructed the classifier (to classify early-stage LUAD patients into C1 or C2 groups) with multiple machine learning and bioinformatic analyses. The 21-gene-based classification model showed high accuracy and strong generalization ability, and it was verified in four independent validation cohorts. In summary, our research provided a new strategy for clinicians to make a quick preliminary assisting diagnosis of early-stage LUAD and make patient classification at the intratumor heterogeneity level. All data, codes, and study processes have been deposited to Github and are available online.

12.
BMC Med Genomics ; 15(1): 33, 2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35193578

RESUMO

BACKGROUND: Precision medicine has increased the accuracy of cancer diagnosis and treatment, especially in the era of cancer immunotherapy. Despite recent advances in cancer immunotherapy, the overall survival rate of advanced NSCLC patients remains low. A better classification in advanced NSCLC is important for developing more effective treatments. METHOD: The calculation of abundances of tumor-infiltrating immune cells (TIICs) was conducted using Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT), xCell (xCELL), Tumor IMmune Estimation Resource (TIMER), Estimate the Proportion of Immune and Cancer cells (EPIC), and Microenvironment Cell Populations-counter (MCP-counter). K-means clustering was used to classify patients, and four machine learning methods (SVM, Randomforest, Adaboost, Xgboost) were used to build the classifiers. Multi-omics datasets (including transcriptomics, DNA methylation, copy number alterations, miRNA profile) and ICI immunotherapy treatment cohorts were obtained from various databases. The drug sensitivity data were derived from PRISM and CTRP databases. RESULTS: In this study, patients with stage 3-4 NSCLC were divided into three clusters according to the abundance of TIICs, and we established classifiers to distinguish these clusters based on different machine learning algorithms (including SVM, RF, Xgboost, and Adaboost). Patients in cluster-2 were found to have a survival advantage and might have a favorable response to immunotherapy. We then constructed an immune-related Poor Prognosis Signature which could successfully predict the advanced NSCLC patient survival, and through epigenetic analysis, we found 3 key molecules (HSPA8, CREB1, RAP1A) which might serve as potential therapeutic targets in cluster-1. In the end, after screening of drug sensitivity data derived from CTRP and PRISM databases, we identified several compounds which might serve as medication for different clusters. CONCLUSIONS: Our study has not only depicted the landscape of different clusters of stage 3-4 NSCLC but presented a treatment strategy for patients with advanced NSCLC.


Assuntos
Biologia Computacional , Neoplasias Pulmonares , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Aprendizado de Máquina , Prognóstico , Microambiente Tumoral/genética
13.
PLoS One ; 16(10): e0253858, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34618818

RESUMO

Research indicates that Staphylococcus aureus colonization in the elderly with predisposing risks is associated with subsequent infection. However, the molecular epidemiology and risk factors for S. aureus colonization among residents and staff in nursing homes (NHs) in China remain unclear. A multicenter study was conducted in three NHs in Shanghai between September 2019 and October 2019. We explored the prevalence, molecular epidemiology, and risk factors for S. aureus colonization. All S. aureus isolates were characterized based on antimicrobial resistance, virulence genes, multilocus sequence typing (MLST), staphylococcus protein A (spa) typing, and staphylococcal cassette chromosome mec (SCCmec) typing. NH records were examined for potential risk factors for S. aureus colonization. S. aureus and methicillin-resistant S. aureus (MRSA) isolates were detected in 109 (100 residents and 9 staff, 19.8%, 109/551) and 28 (24 residents and 4 staff, 5.1%, 28/551) subjects among 496 residents and 55 staff screened, respectively. Compared to methicillin-susceptible S. aureus isolates, all 30 MRSA isolates had higher resistance rates to most antibiotics except minocycline, rifampicin, linezolid, vancomycin, and teicoplanin. Sequence type (ST) 1 (21.3%) was the most common sequence type, and t127 (20.5%) was the most common spa type among 122 S. aureus isolates. SCCmec type I (70%) was the dominant clone among all MRSA isolates. CC1 (26/122, 21.3%) was the predominant complex clone (CC), followed by CC398 (25/122, 20.5%), CC5 (20/122, 16.4%) and CC188 (18/122, 14.8%). Female sex (OR, 1.70; 95% CI, 1.04-2.79; P = 0.036) and invasive devices (OR, 2.19; 95% CI, 1.26-3.81; P = 0.006) were independently associated with S. aureus colonization.


Assuntos
Staphylococcus aureus Resistente à Meticilina/genética , Infecções Estafilocócicas/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , China , Análise Fatorial , Feminino , Genótipo , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Epidemiologia Molecular/métodos , Tipagem de Sequências Multilocus , Casas de Saúde , Fatores de Risco , Infecções Estafilocócicas/tratamento farmacológico , Fatores de Virulência/genética
14.
Front Cell Infect Microbiol ; 11: 653983, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485168

RESUMO

Urinary tract infection (UTI) is one of the most common bacterial infections and UTI is the most common extraintestinal infectious disease entity in women worldwide. Uropathogenic Escherichia coli (UPEC) is the leading cause of UTI. While antimicrobial resistance has emerged as one of the principal problems of UTI, little is known about the epidemiology of UPEC isolated from female patients in Shanghai. This study aimed to describe the antimicrobial resistance and molecular epidemiology of UPEC isolated from female patients in Shanghai, China. UPEC isolates were collected from female patients from July 2019 to June 2020 in Shanghai and a total of 151 isolates were obtained randomly. Antimicrobial susceptibility testing was performed using the disk diffusion method. Multilocus sequencing type, phylogenetic groups, antimicrobial resistance genes, and virulence genes were detected by polymerase chain reaction. In our study, no carbapenem-resistant isolates were found, but fluoroquinolone-resistant and multi-drug resistant UPEC accounted for 62.25% and 42.38%, respectively. The phylogenetic group B2 (58.94%) predominated, followed by phylogenetic group D (26.49%). The most prevalent sequence type was ST1193 (25.83%), which was first reported in Shanghai. The rate of extended-spectrum ß-lactamase (ESBL)-positive isolates was 39.74% and the dominant ESBL genotype was blaCTX-M-14 (21/60), followed by blaCTX-M-55 (12/60). Mutations in gyrA were detected in the majority of fluoroquinolone-resistant isolates (90/94), followed by parC (85/94) and parE (71/94). The aac (3) -IIa was also found in 85% of aminoglycoside resistance isolates. Among 151 UPEC isolates, the common virulence genes were csgA (97.35%), fimH (92.72%), sitA (82.12%), and malX (65.56%). In conclusion, the high antimicrobial resistance of UPEC isolated from female patients, harboring a series of virulence genes, are troublesome for medical practitioners in Shanghai. At present, the prevalent ST1193 and emerging blaCTX-M-55 make UTI therapy more challenging.


Assuntos
Infecções por Escherichia coli , Infecções Urinárias , Escherichia coli Uropatogênica , Antibacterianos/farmacologia , China/epidemiologia , Farmacorresistência Bacteriana , Infecções por Escherichia coli/epidemiologia , Feminino , Humanos , Epidemiologia Molecular , Filogenia , Infecções Urinárias/epidemiologia , Escherichia coli Uropatogênica/genética , beta-Lactamases/genética
15.
Front Genet ; 12: 619821, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122500

RESUMO

Lung adenocarcinoma has entered into an era of immunotherapy with the development of immune checkpoint inhibitors (ICIs). The identification of immune subtype is crucial to prolonging survival in patients. The tumor microenvironment (TME) and metabolism have a profound impact on prognosis and therapy. The majority of previous studies focused on only one aspect, while both of them are essential to the understanding of tumorigenesis and development. We hypothesized that lung adenocarcinoma can be stratified into immune subgroups with alterations in the TME infiltration. We aimed to explore the "TME-Metabolism-Risk" patterns in each subtypes and the mechanism behind. Glycolysis and cholesterol were selected for the analysis of metabolic states based on the first half of the study. Bioinformatic analysis was performed to investigate the transcriptomic and clinical data integrated by three lung adenocarcinoma cohorts (GSE30219, GSE31210, GSE37745, N = 415). The results were validated in an independent cohort (GSE50081, N = 127). In total, 415 lung adenocarcinoma samples were integrated and analyzed. Four major immune subtypes were indentified using bioinformatic analysis. Subtype NC1, characterized by a high level of glycolysis, with extremely low microenvironment cell infiltration. Subtype NC2, characterized by the "Silence" and "Cholesterol biosynthesis Predominant" metabolic states, with a middle degree infiltration of microenvironment cell. Subtype NC3, characterized by the lack of "Cholesterol biosynthesis Predominant" metabolic state, with abundant microenvironment cell infiltration. Subtype NC4, characterized by "Mixed" metabolic state, with a relatively low microenvironment cell infiltration. Least absolute shrinkage and selection operator (LASSO) regression and multivariate analyses were performed to calculate the risk of each sample, and we attempted to find out the potential immune escape mechanism in different subtypes. The result revealed that the lack of immune cells infiltration might contribute to the immune escape in subtypes NC1 and NC4. NC3 was characterized by the high expression of immune checkpoint molecules and fibroblasts. NC2 had defects in activation of innate immune cells. There existed an obviously survival advantage in subtype NC2. Gene set enrichment analysis (GSEA) and Gene Ontology analysis indicated that the PI3K-AKT-mTOR, TGF-ß, MYC-related pathways might be correlated with this phenomenon. In addition, some differentially expressed genes (DEGs) were indentified in subtype NC3, which might be potential targets for survival phenotype transformation.

16.
Opt Express ; 29(9): 12867-12879, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33985033

RESUMO

Phase measuring deflectometry (PMD) is an effective technique for three-dimensional measurement of specular surfaces. However, the ambiguity of monoscopic PMD and the time-consuming searching process of stereoscopic PMD are challenges for specular surface reconstruction. To solve it, we propose an iterative reconstruction algorithm for the stereoscopic phase measuring deflectometry system free of the time-consuming searching process for each pixel. An arbitrary seed point on the specular surface is accurately obtained via a coarse-to-fine optimization means without any other expensive and complicate auxiliaries. Then, a plane with the height of seed point is set as the initial surface form for the iteration, in which the pinhole model is used to find the linear relation to update the surface form. The converging height is the output as the final result. Simulations and experiments verify the feasibility and efficiency of our proposed method based on the stereoscopic phase measuring deflectometry system. The accuracy and robustness are comprehensively evaluated as well.

17.
Technol Cancer Res Treat ; 20: 1533033821997819, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33715525

RESUMO

BACKGROUND: It was controversial that whether LUAD patients with brain metastases (BMs) and EGFR sensitive mutations should be conducted using brain radiotherapy when treated with first-generation EGFR-TKI. Herein, a retrospective study was designed to compare the efficacy of first-generation EGFR-TKI combined with brain radiotherapy and EGFR-TKI alone as first-line treatment for these LUAD patients. PATIENTS AND METHODS: We retrospectively analyzed the status of patients with advanced LUAD carrying EGFR sensitive mutations who received first-generation EGFR-TKI treatment in our center. iPFS was the first time of intracranial progression or death from the diagnosis of BMs, PFS was the time of progression of any site or death from the diagnosis of BMs, and OS was the time of confirmed BMs to death or the last follow-up time. Differences in characteristics between groups were compared using the Chi-square test. The Kaplan-Meier method was used to calculate the iPFS, PFS, and OS. Univariate analysis, multivariate analysis, and subgroup analysis were conducted by Cox regression model. RESULTS: There were 77 patients (77/134, 57.5%) in the TKI + RT group and 57 patients (57/134, 42.5%) in the TKI group. TKI + RT group had a significant higher intracranial ORR and DCR, and the combination therapy was independently significantly associated with a longer iPFS (18.9 vs. 10.5 months, P = 0.0009), systematic PFS (12.5 vs. 8.4 months, P = 0.0071) and OS (30.8 vs. 22.7 months, P = 0.0183). Females, non-smokers, and younger patients benefited more from the combination therapy. Subgroup analysis demonstrated that the combination therapy could improve the iPFS in patients with more than 3 BMs (P = 0.005); however, it couldn't improve the OS for these patients. CONCLUSION: Our study confirmed the effect of the combination of EGFR-TKI and brain radiotherapy as first-line treatment for LUAD patients with BMs and EGFR sensitive mutations.


Assuntos
Adenocarcinoma de Pulmão/patologia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Irradiação Craniana , Inibidores de Proteínas Quinases/uso terapêutico , Adenocarcinoma de Pulmão/etiologia , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Terapia Combinada , Irradiação Craniana/efeitos adversos , Irradiação Craniana/métodos , Gerenciamento Clínico , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Inibidores de Proteínas Quinases/farmacologia , Estudos Retrospectivos , Resultado do Tratamento
18.
Int Immunopharmacol ; 94: 107416, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33676174

RESUMO

Immune escape and low response to immunotherapy are crucial challenges in present lung cancer treatment. In this study, we constructed a new immune-related classifier based on CXCL13/CXCR5, an important tumor microenvironment component and strongly related with the formation of tertiary lymphoid structures (TLSs) in tumor microenvironment. With the classifier, we divided patients into two main clusters and each cluster was further divided into subcluster (A1, A2, B1, B2, B3). In the later analysis, we noticed that patients in subcluster B3 had a distinct advantage over patients in A1 in survival time and immune infiltration, suggesting a more favorable response to immunotherapy. Moreover, we demonstrated the genetic and epigenetic regulation related to the subclusters and recovered four key differentially expressed genes (ERBB4, GRIN2A, IL2RA, CCND2). With several experiments, we verified the unique role of CCND2 in tumor metastasis and T cell apoptosis. Overexpressing CCND2 could significantly impair cancer cell abilities of migration and invasion and downregulate PD-1/PD-L1 signaling, which may be the cause of T cell apoptosis reduction. In the end, we constructed a regression risk model that could successfully predict ICI response. To sum up, our study established new stratification models that can successfully predict patient survival and response to ICI. And using integrative analysis of multi-omics data, four key DEGs were noticed, and CCND2, one of the four genes, was identified as a potential treatment target because of its effect in tumor metastasis and T cell apoptosis.


Assuntos
Adenocarcinoma de Pulmão/genética , Quimiocina CXCL13/genética , Ciclina D2/genética , Neoplasias Pulmonares/genética , Receptores CXCR5/genética , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Apoptose/genética , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Masculino , Linfócitos T/imunologia
19.
Appl Opt ; 59(33): 10574-10583, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33361992

RESUMO

Speckle dots have the advantage of easy projection, which makes them good candidate features of structured light (SL) cameras, such as Kinect v1. However, they generally yield poor accuracy due to block matching. To improve their accuracy, this paper proposes a dot-coded SL, the coding information of which is added into dot distribution. Some of the dots are arranged regularly to provide easy-to-locate corner features, while others are specially designed to form different shapes of unique identification. A Gaussian-cross module and a simplified ResNet have been proposed to conduct robust decoding. Various experiments are performed to verify the accuracy and robustness of our framework.

20.
Opt Express ; 28(22): 32978-33001, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33114970

RESUMO

Compared with existing depth cameras, such as RGB-D, RealSense and Kinect, stripe-based structured light (SL) has the potential for micrometer-level 3D measurement; this can be attributed to its higher coding capacity. While surface texture, high-reflective region, and occlusion remain some of the main sources leading to degraded reconstruction quality in complex objects, methods that are only based on SL cannot completely solve such problems in complex object reconstruction. In this paper, we developed an advanced fusion strategy for the reconstruction of complex objects in micrometer-level 3D measurement. This includes solving the above-mentioned inherent problems of a stripe-based SL system with the aid of photometric stereo (PS). Firstly, to improve the robustness of decoding and eliminate the effects of noise and occlusion on stripe detection, a novel scene-adaptive decoding algorithm based on a binary tree was proposed. Further, a robust and practical calibration method for area light sources in the PS system, which utilizes the absolute depth information from SL system, was introduced. A piecewise integration algorithm, which is based on a subregion divided by Gray code, was proposed by combining the depth values from SL with the normal information from PS. Remarkably, this method eliminates the effects of surface texture and high-reflective region on the reconstruction quality and improves the resolution to camera-level resolution. In experimental parts, a regular cylinder was reconstructed to demonstrate micrometer-level measurement accuracy and resolution enhancement by the proposed method. Then, improvement of the reconstruction accuracy for objects with surface texture was validated with a regular pyramid that had textures on it and a white paper with characters printed on it. Lastly, a complex object containing multiple phenomena was reconstructed with the newly proposed method to show its effectiveness for micrometer-level 3D measurement in complex objects. Evaluation of our proposed method shows the improvement of the proposed method on the existing methods being used for micrometer-level 3D measurement in complex objects.

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