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BACKGROUND: Patients with diabetic feet are prone to be infected due to the impaired immune system. However, the prognostic outcome of different microbial infections remains controversial. Identification and rapid screening of the pathogenic microorganisms that pose the greatest threat to the prognosis of patients with diabetic foot infections (DFIs) is critical. METHODS: Clinical data were statistically analyzed, which were obtained from 522 patients with DFIs, including pathogenic bacterial culture results and treatment outcomes at the last return visit. In addition, a loop-mediated isothermal amplification (LAMP) detection method was developed to identify the prevalent subtype of methicillin-resistant Staphylococcus aureus (MRSA) in DFIs patients. This study was approved by the Ethics Committee of Nanfang Hospital (NFEC-202012-K6) and registered on ClinicalTrials.gov (NCT04916457) on June 1, 2021. RESULTS: We found that the proportion of patients with infections of Staphylococcus aureus (S. aureus) and MRSA was 27.7% (145/522) and 33.7% (49/145), respectively. Additionally, the incidence of osteomyelitis was 46.9% (23/49) and amputation/disability was 40.8% (20/49) in patients with MRSA infection, which were significantly higher compared to patients with other types of bacterial infections such as methicillin-susceptible Staphylococcus aureus (MSSA). Notably, we demonstrated that the main prevalent subtype of MRSA in DFIs patients in our hospital was Staphylococcal chromosomal cassettes mec (SCCmec) type II. In addition, it only takes 1.5 h to complete the entire experimental procedure in this LAMP assay, providing high sensitivity (100%) and specificity (77.8%) in hospitalized patients with DFIs. CONCLUSIONS: We demonstrated there is a very high rate of MRSA isolation in patients with DFIs and revealed that patients infected with MRSA are at a higher risk of developing osteomyelitis, and amputation or disability. Importantly, we have developed a method for quickly screening newly admitted patients for MRSA.
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Diabetes Mellitus , Pé Diabético , Staphylococcus aureus Resistente à Meticilina , Osteomielite , Infecções Estafilocócicas , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus/genética , Antibacterianos/uso terapêutico , Prevalência , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/tratamento farmacológico , Testes de Sensibilidade Microbiana , Diabetes Mellitus/tratamento farmacológicoRESUMO
BACKGROUND: Accurately distinguishing between pulmonary infection and colonization in patients with Acinetobacter baumannii is of utmost importance to optimize treatment and prevent antibiotic abuse or inadequate therapy. An efficient automated sorting tool could prompt individualized interventions and enhance overall patient outcomes. This study aims to develop a robust machine learning classification model using a combination of time-series chest radiographs and laboratory data to accurately classify pulmonary status caused by Acinetobacter baumannii. METHODS: We proposed nested logistic regression models based on different time-series data to automatically classify the pulmonary status of patients with Acinetobacter baumannii. Advanced features were extracted from the time-series data of hospitalized patients, encompassing dynamic pneumonia indicators observed on chest radiographs and laboratory indicator values recorded at three specific time points. RESULTS: Data of 152 patients with Acinetobacter baumannii cultured from sputum or alveolar lavage fluid were retrospectively analyzed. Our model with multiple time-series data demonstrated a higher performance of AUC (0.850, with a 95% confidence interval of [0.638-0.873]), an accuracy of 0.761, a sensitivity of 0.833. The model, which only incorporated a single time point feature, achieved an AUC of 0.741. The influential model variables included difference in the chest radiograph pneumonia score. CONCLUSION: Dynamic assessment of time-series chest radiographs and laboratory data using machine learning allowed for accurate classification of colonization and infection with Acinetobacter baumannii. This demonstrates the potential to help clinicians provide individualized treatment through early detection.
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Infecções por Acinetobacter , Acinetobacter baumannii , Pneumonia , Humanos , Estudos Retrospectivos , Infecções por Acinetobacter/diagnóstico por imagem , Antibacterianos/uso terapêutico , Pneumonia/tratamento farmacológicoRESUMO
BACKGROUND Exploring the factors that impact the time from symptom onset to first medical contact (S2FMC) is crucial for improving outcomes in elderly patients diagnosed with acute ST-segment elevation myocardial infarction (STEMI). This study conducted a retrospective analysis on 282 patients who underwent emergency percutaneous coronary intervention (PCI) or percutaneous transluminal coronary angioplasty (PTCA) in Guangzhou City District to identify significant factors affecting S2FMC. MATERIAL AND METHODS A retrospective analysis was conducted on 282 patients with STEMI who underwent emergency percutaneous coronary intervention (PCI). Descriptive statistics, univariate and multivariate Cox regression analyses were used to identify significant factors affecting S2FMC. Additionally, interactions between risk factors were examined using multivariate logistic regression and the structural equation model (SEM). RESULTS Age (HR=0.984, 95% CI: 0.975-0.993), nature of chest pain (HR=2.561, 95% CI: 1.900-3.458), admission mode (HR=1.805, 95% CI: 1.358-2.400), and vascular characteristics (HR=1.246, 95% CI: 1.069-1.451) were independent influencing factors for S2FMC. Persistent chest tightness/pain, EMS admission, and vascular characteristics (RCADL or LCADL) played a protective role in S2FMC. Among the influencing factors, vascular characteristics (OR=1.072, 95% CI: 1.008-1.141) had an independent effect on the nature of chest pain. Meanwhile, the nature of chest pain (OR=1.148, 95% CI: 1.015-1.298) was an independent influencing factor in the admission mode. CONCLUSIONS Patients with persistent chest tightness/pain, EMS admission, and vascular characteristics (RCADL or LCADL) experienced shorter S2FMC and higher compliance rate (S2FMC ≤180 min). At the same time, age and other vascular features played an inverse role. This study proposes enhancing follow-up and monitoring measures, and shows the consequences of intermittent chest pain should not be disregarded.
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Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Idoso , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Intervenção Coronária Percutânea/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Fatores de Tempo , Dor no Peito/etiologiaRESUMO
At present, it is still a challenge to prepare multifunctional composite nanomaterials with simple composition and favorable structure. Here, multifunctional Fe3O4@nitrogen-doped carbon (N-C) nanocomposites with hollow porous core-shell structure and significant electrochemical, adsorption and sensing performances were successfully synthesized through the hydrothermal method, polymer coating, then thermal annealing process in nitrogen (N2) and lastly etching in hydrochloric acid (HCl). The morphologies and properties of the as-obtained Fe3O4@N-C nanocomposites were markedly affected by the etching time of HCl. When the Fe3O4@N-C nanocomposites after etching for 30 min (Fe3O4@N-C-3) were applied as the anodes for lithium-ion batteries (LIBs), the invertible capacity could reach 1772 mA h g-1 after 100 cycles at the current density of 0.2 A g-1, which is much better than that of Fe3O4@N-C nanocomposites etched, respectively, for 15 min and 45 min (948 mA h g-1 and 1127 mA h g-1). Additionally, the hollow porous Fe3O4@N-C-3 nanocomposites also exhibited superior rate capacity (950 mA h g-1 at 0.6 A g-1). The excellent electrochemical properties of Fe3O4@N-C nanocomposites are attributed to their distinctive hollow porous core-shell structure and appropriate N-doped carbon coating, which could provide high-efficiency transmission channels for ions/electrons, improve the structural stability and accommodate the volume variation in the repeated Li insertion/extraction procedure. In addition, the Fe3O4@N-C nanocomposites etched by HCl for different lengths of time, especially Fe3O4@N-C-3 nanocomposites, also show good performance as adsorbents for the removal of the organic dye (methyl orange, MO) and surface-enhanced Raman scattering (SERS) substrates for the determination of a pesticide (thiram). This work provides reference for the design and preparation of multifunctional materials with peculiar pore structure and uncomplicated composition.
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Lítio , Nanocompostos , Porosidade , Análise Espectral Raman , Eletrodos , Carbono , Ácido Clorídrico , Íons , NitrogênioRESUMO
The complex physiological environment and inherent self-healing function of tumors make it difficult to eliminate malignant tumors by single therapy. In order to enhance the efficacy of antitumor therapy, it is significant and challenging to realize multi-mode combination therapy by utilizing/improving the adverse factors of the tumor microenvironment (TME). In this study, a novel Fe3O4@Au/PPy nanoplatform loaded with a chemotherapy drug (DOX) and responsive to TME, near-infrared (NIR) laser and magnetic field was designed for the combination enhancement of eliminating the tumor. The Fe2+ released at the low pH in TME can react with endogenous H2O2 to induce toxic hydroxyl radicals (·OH) for chemodynamic therapy (CDT). At the same time, the generated Fe3+ could deplete overexpressed glutathione (GSH) at the tumor site to prevent reactive oxygen species (ROS) from being restored while producing Fe2+ for CDT. The designed Fe3O4@Au/PPy nanoplatform had high photothermal (PT) conversion efficiency and photodynamic therapy (PDT) performance under NIR light excitation, which can promote CDT efficiency and produce more toxic ROS. To maximize the cancer-killing efficiency, the nanoplatform can be successfully loaded with the chemotherapeutic drug DOX, which can be efficiently released under NIR excitation and induction of slight acidity at the tumor site. In addition, the nanoplatform also possessed high saturation magnetization (20 emu/g), indicating a potential magnetic targeting function. In vivo and in vitro results identified that the Fe3O4@Au/PPy-DOX nanoplatform had good biocompatibility and magnetic-targeted synergetic CDT/PDT/PTT/chemotherapy antitumor effects, which were much better than those of the corresponding mono/bi/tri-therapies. This work provides a new approach for designing intelligent TME-mediated nanoplatforms for synergistically enhancing tumor therapy.
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Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Glutationa , Humanos , Peróxido de Hidrogênio , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Espécies Reativas de Oxigênio , Microambiente TumoralRESUMO
The [Aux Ag16-x (SAdm)8 (Dppe)2 ] nanocluster with aggregation-induced emission (AIE) was synthesized from a non-fluorescent [Au9 Ag12 (SAdm)4 (Dppm)6 Cl6 ](SbF6 )3 nanocluster via a ligand-exchange engineering (Dppe=1,2-Bis(diphenylphosphino)ethane, Dppm=Bis(diphenylphosphino)methane, HSAdm=1-Adamantanethiol). The nanocluster has a Au-doped icosahedral Aux Ag13-x core, capped by two Ag(SR)3 , one Ag(SR)2 and two Dppe ligands. By changing the achiral Dppe ligand into a chiral dbpb ligand ((2S,3S)-(-)-Bis(diphenylphosphino)butane or (2R,3R)-(+)-2,3-Bis(diphenylphosphino)butane), chiral nanoclusters are obtained. ESI-MS and UV-vis spectroscopy were performed to track the reaction. This work provides guidance for the construction of new clusters by etching clusters with multidentate phosphine ligands.
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COVID-19 has spread globally, causing a pandemic and medical interruptions. As more countries control the epidemic, the resumption of work is imperative. However, asymptomatic carriers become the main source of infection. After several months of recovery, Wuhan had much experience with facing the challenge of work resumption. The purpose of this study was to investigate the safety of the resumption strategies, as well as the outcome of the resumption efforts, in the early post-epidemic period. A retrospective study was conducted in patients admitted between April 8 and June 30 to the neurosurgery department of Tongji Hospital, Wuhan. The medical information, past medical history, COVID-19 tests, laboratory parameters, CT results, and management were reviewed and recorded. 768 patients were admitted to the neurosurgery department at Tongji Hospital, and none of them became new infections. Our department recovered to 70% efficiency one month after the resumption of work. Two patients were found to have asymptomatic infections in the outpatient department. Two patients who recovered from COVID-19 underwent the surgery without recurrence of COVID-19. Tumor patients accounted for more than 50% of the surgery patients in the early period. It is feasible and helpful to follow our strict admission algorithm in the early post-epidemic period, even though the challenges of asymptomatic infectors exist. Two COVID-19 tests in 3 days are suggested within the early period. Protective downgrades should be based on the testing of asymptomatic patients in the area. Recovered COVID-19 patients can undergo surgery without recurrence.
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COVID-19 , Neurocirurgia , China/epidemiologia , Humanos , Pandemias , Estudos Retrospectivos , SARS-CoV-2RESUMO
Various antibiotic-resistant bacteria (ARB) are known to induce repeated pulmonary infections and increase morbidity and mortality. A thorough knowledge of antibiotic resistance is imperative for clinical practice to treat resistant pulmonary infections. In this study, we used a reads-based method and an assembly-based method according to the metagenomic next-generation sequencing (mNGS) data to reveal the spectra of ARB and corresponding antibiotic resistance genes (ARGs) in samples from patients with pulmonary infections. A total of 151 clinical samples from 144 patients with pulmonary infections were collected for retrospective analysis. The ARB and ARGs detection performance was compared by the reads-based method and assembly-based method with the culture method and antibiotic susceptibility testing (AST), respectively. In addition, ARGs and the attribution relationship of common ARB were analyzed by the two methods. The comparison results showed that the assembly-based method could assist in determining pathogens detected by the reads-based method as true ARB and improve the predictive capabilities (46% > 13%). ARG-ARB network analysis revealed that assembly-based method could promote determining clear ARG-bacteria attribution and 101 ARGs were detected both in two methods. 25 ARB were obtained by both methods, of which the most predominant ARB and its ARGs in the samples of pulmonary infections were Acinetobacter baumannii (ade), Pseudomonas aeruginosa (mex), Klebsiella pneumoniae (emr), and Stenotrophomonas maltophilia (sme). Collectively, our findings demonstrated that the assembly-based method could be a supplement to the reads-based method and uncovered pulmonary infection-associated ARB and ARGs as potential antibiotic treatment targets.
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Antibacterianos , Bactérias , Farmacorresistência Bacteriana , Sequenciamento de Nucleotídeos em Larga Escala , Microbiota , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias/genética , Bactérias/efeitos dos fármacos , Bactérias/classificação , Bactérias/isolamento & purificação , Microbiota/genética , Microbiota/efeitos dos fármacos , Estudos Retrospectivos , Farmacorresistência Bacteriana/genética , Metagenômica/métodos , Testes de Sensibilidade Microbiana , Infecções Respiratórias/microbiologia , Infecções Respiratórias/tratamento farmacológico , Genes Bacterianos/genética , Masculino , Feminino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Students' academic performance and learning experiences are crucial in school education, yet their relationships with instructional characteristics remain an open question. AIMS: The present study examined how cognitive activation and teacher support were associated with students' academic emotions and achievement in math classrooms via domain- and task-specific self-efficacy. SAMPLE: In total, 5388 eighth graders from central China participated in this study. METHODS: Cognitive activation, teacher support, math-related enjoyment and anxiety, and domain- and task-specific self-efficacy were measured with self-reported student questionnaires. The math achievement was measured with a standardized test. RESULTS: Our findings showed that the two instructional characteristics were positively related to math achievement and enjoyment but negatively related to math anxiety, with the mediation effects of task- and domain-specific self-efficacy. In detail, cognitive activation had a stronger relationship with math anxiety through task-specific self-efficacy than domain-specific self-efficacy. Whereas, cognitive activation had a greater linkage with math enjoyment through domain-specific self-efficacy than task-specific self-efficacy. In addition, teacher support had a greater association with learning outcomes through domain-specific self-efficacy than task-specific self-efficacy. CONCLUSIONS: The relational mechanism of cognitive activation and teacher support on math achievement and academic emotions were differentially mediated by task- and domain-specific self-efficacy in Chinese math classrooms.
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Autoeficácia , Estudantes , Humanos , Estudantes/psicologia , Emoções , Ansiedade/psicologia , LogroRESUMO
This study investigated the mathematical problem-solving ability of 42,644 ninth-grade students who participated in regional education quality health monitoring from Z province in East China and the factors which influence their performance of mathematical problem-solving. The results are as follows: (1) ~96% of the students' mathematics problem-solving ability meets the basic academic requirements of the mathematics curriculum standards; (2) boys and children without siblings performed better, and urban students performed significantly better than county and rural students; (3) ~28% of students' mathematical problem-solving performance came from inter-school variability; urban and rural backgrounds had a greater impact on mathematical problem-solving than did teaching factors, while teaching self-efficacy had the least impact among the school-level influencing factors. In contrast, the influence of individual non-intelligence factors was higher than that of student background variables, including a greater positive effect of self-efficacy and a greater negative effect of mathematics anxiety.
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Normally, HIV-1 enters into CD4+ cells through membrane fusion, and newly synthesized HIV-1 viral proteins assemble on the plasma membrane to form viral particles and bud out. In the previous study, we found host factor coiled-coil domain containing protein 8 (CCDC8) can strongly inhibit HIV-1 production, but the underline mechanism is not clear. Here we show that overexpression of CCDC8 reverses the normal HIV-1 production process, and causes newly assembled HIV-1 Gag particles to be endocytosed on the plasma membrane, rather than budding out. Live-cell imaging system captured the moment of CCDC8-mediated Gag internalization on the plasma membrane, and the speed of Gag turnover is up to 1.53 µm/s, much faster than Gag assembly on the plasma membrane. After Gag internalization, it accumulates in the cellular organelle-lysosome for degradation, but not proteasome, autophagosome, endoplasmic reticulum, clathrin or recycling endosome. In addition, CCDC8 is a membrane-associated protein, and N-terminal of CCDC8 is very important for membrane binding, and also important for inhibition of Gag assembly. C-terminal deletion of CCDC8 has a little effect on anti-HIV-1 effect. Moreover, CCDC8 is phosphorylated at amino acid threonine T87 and serine S261, and mono-methylated at lysine K491. Alanine mutations of T87A, S261A and K491A singly or in combination do not affect CCDC8 anti-HIV activity. In conclusion, overexpression of CCDC8 can cause newly assembled HIV-1 Gag particles on the plasma membrane to be endocytosed and degraded in lysosome.
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Proteínas de Transporte/fisiologia , Lisossomos/metabolismo , Vírion/metabolismo , Montagem de Vírus , Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética , Linfócitos T CD4-Positivos/metabolismo , Membrana Celular/metabolismo , Endocitose , Retículo Endoplasmático/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Soropositividade para HIV , HIV-1/fisiologia , Humanos , Lisina/química , Filogenia , Processamento de Proteína Pós-TraducionalRESUMO
Τhe photocatalytic activity in the range of visible light wavelengths and the thermal stability of the structure were significantly enhanced in Si, N co-doped nano-sized TiO2, and synthesized through high-energy mechanical milling of TiO2 and SiO2 powders, which was followed by calcination at 600 °C in an ammonia atmosphere. High-energy mechanical milling had a pronounced effect on the mixing and the reaction between the starting powders and greatly favored the transformation of the resultant powder mixture into an amorphous phase that contained a large number of evenly-dispersed nanocrystalline TiO2 particles as anatase seeds. The experimental results suggest that the elements were homogeneously dispersed at an atomic level in this amorphous phase. After calcination, most of the amorphous phase was crystallized, which resulted in a unique nano-sized crystalline-core/disordered-shell morphology. This novel experimental process is simple, template-free, and provides features of high reproducibility in large-scale industrial production.
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C-C chemokine receptor type 5 (CCR5) is the main co-receptor for HIV entry into the target CD4+ cells, and homozygous CCR5Δ32/Δ32 cells are resistant to CCR5-tropic HIV infection. However, the CCR5Δ32/Δ32 homozygous donors in populations are rare. Here we developed a simple approach to induce CCR5Δ32/Δ32 homozygotes through CRISPR-Cas9 genome-editing technology. Designing a pair of single-guide RNA targeting the flank region of the CCR5Δ32 mutation locus, we applied the CRISPR-Cas9 and lentiviral packaging system to successfully convert wild-type CCR5 into CCR5Δ32/Δ32 homozygotes in the human Jurkat CD4+ cell line and primary CD4+ cells, exactly the same as the naturally occurring CCR5Δ32/Δ32 mutation. The successful rate is up to 20% in Jurkat cells but less in primary CD4+ cells. The modified CCR5Δ32/Δ32 CD4+ cells are resistant to CCR5-tropic HIV infection. Whole-genome sequencing revealed no apparent off-target sites. This approach has the promise to promote HIV/AIDS therapy from the only cured unique Berlin patient to a routine autologous cell-based therapy.
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C-C chemokine receptor 5 (CCR5) is a receptor for chemokines and a co-receptor for HIV-1 entry into the target CD4+ cells. CCR5 delta 32 deletion is a loss-of-function mutation, resistant to HIV-1 infection. We tried to induce the CCR5 delta 32 mutation harnessing the genome editing technique, CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR and CRISPR associated protein 9, Cas9) in the commonly used cell line human embryonic kidney HEK 293T cells. Surprisingly, we found that HEK293T cells are heterozygous for CCR5 delta 32 mutation, in contrast to the wild type CCR5 cells, human acute T cell leukemia cell line Jurkat and human breast adenocarcinoma cell line MDA-MB-231 cells. This finding indicates that at least one human cell line is heterozygous for the CCR5 delta 32 mutation. We also found that in PCR amplification, wild type CCR5 DNA and mutant delta 32 DNA can form mismatched heteroduplex and move slowly in gel electrophoresis.