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1.
Artigo em Inglês | MEDLINE | ID: mdl-38717890

RESUMO

The digital construction of cultural heritage promotes communication and sharing of digital cultural resources across time and space. Digital storage serves as the foundation for the digital construction of cultural artifacts. In the digital storage of Dunhuang murals, image stitching plays a critical role in restoring the complete image of the cave murals. Traditional image stitching methods are constrained by the detection accuracy of feature points and are not fit for stitching low-texture murals. Despite deep learning-based image stitching methods, parallax misalignment and ghosting are still prevalent issues. For this reason, we perform the first Dunhuang mural stitching based on deep learning in this paper. This is in response to the need for digitizing and storing Dunhuang murals. Two mural stitching datasets are constructed, and we design a progressive regression image alignment network and a feature differential reconstruction soft-coded seam stitching network. We also introduce a soft-coded seam quality evaluation method. The algorithm presented in this paper achieves state-of-the-art alignment and stitching performance in the mural stitching task through unsupervised learning with a smaller number of model parameters, which provides technical support for the digitization and preservation of Dunhuang murals. The codes and models will be available at https://github.com/MmelodYy/DunHuangStitch.

2.
J Med Virol ; 96(5): e29662, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38727085

RESUMO

This study investigated the clinical effectiveness of nirmatrelvir plus ritonavir (NMV-r) on short-term outcome and the risk of postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) among pediatric patients with coronavirus disease 2019 (COVID-19). This retrospective cohort study used the TriNetX research network to identify pediatric patients between 12 and 18 years with COVID-19 between January 1, 2022 and August 31, 2023. The propensity score matching (PSM) method was used to match patients receiving NMV-r (NMV-r group) with those who did not receive NMV-r (control group). Two cohorts comprising 633 patients each (NMV-r and control groups), with balanced baseline characteristics, were identified using the PSM method. During the initial 30 days, the NMV-r group showed a lower incidence of all-cause hospitalization, mortality, or ED visits (hazard ratio [HR] = 0.546, 95% confidence interval [CI]: 0.372-0.799, p = 0.002). Additionally, the NMV-r group had a significantly lower risk of all-cause hospitalization compared with the control group (HR = 0.463, 95% CI: 0.269-0.798), with no deaths occurring in either group. In the 30-180-day follow-up period, the NMV-r group exhibited a non-significantly lower incidence of post-acute sequelae of SARS-CoV-2 infection (PASC), encompassing symptoms such as fatigue, cardiopulmonary symptoms, pain, cognitive impairments, headache, dizziness, sleep disorders, anxiety, and depression, compared to the control group. This study underscores the potential effectiveness of NMV-r in treating high-risk pediatric patients with COVID-19, demonstrating significant reductions in short-term adverse outcomes such as emergency department visits, hospitalization, or mortality within the initial 30-day period. Additionally, NMV-r shows promise in potentially preventing the development of PASC.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Ritonavir , Humanos , Ritonavir/uso terapêutico , Masculino , Feminino , Criança , Estudos Retrospectivos , Adolescente , Resultado do Tratamento , COVID-19/mortalidade , Hospitalização/estatística & dados numéricos , SARS-CoV-2 , Antivirais/uso terapêutico , Quimioterapia Combinada , Síndrome de COVID-19 Pós-Aguda
3.
BMC Genomics ; 25(1): 466, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741045

RESUMO

BACKGROUND: Protein-protein interactions (PPIs) hold significant importance in biology, with precise PPI prediction as a pivotal factor in comprehending cellular processes and facilitating drug design. However, experimental determination of PPIs is laborious, time-consuming, and often constrained by technical limitations. METHODS: We introduce a new node representation method based on initial information fusion, called FFANE, which amalgamates PPI networks and protein sequence data to enhance the precision of PPIs' prediction. A Gaussian kernel similarity matrix is initially established by leveraging protein structural resemblances. Concurrently, protein sequence similarities are gauged using the Levenshtein distance, enabling the capture of diverse protein attributes. Subsequently, to construct an initial information matrix, these two feature matrices are merged by employing weighted fusion to achieve an organic amalgamation of structural and sequence details. To gain a more profound understanding of the amalgamated features, a Stacked Autoencoder (SAE) is employed for encoding learning, thereby yielding more representative feature representations. Ultimately, classification models are trained to predict PPIs by using the well-learned fusion feature. RESULTS: When employing 5-fold cross-validation experiments on SVM, our proposed method achieved average accuracies of 94.28%, 97.69%, and 84.05% in terms of Saccharomyces cerevisiae, Homo sapiens, and Helicobacter pylori datasets, respectively. CONCLUSION: Experimental findings across various authentic datasets validate the efficacy and superiority of this fusion feature representation approach, underscoring its potential value in bioinformatics.


Assuntos
Biologia Computacional , Mapeamento de Interação de Proteínas , Mapeamento de Interação de Proteínas/métodos , Biologia Computacional/métodos , Algoritmos , Helicobacter pylori/metabolismo , Helicobacter pylori/genética , Máquina de Vetores de Suporte , Proteínas/metabolismo , Proteínas/química , Humanos , Mapas de Interação de Proteínas , Bases de Dados de Proteínas
4.
Front Neurosci ; 18: 1357269, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38516315

RESUMO

Introduction: Chronic lower back pain (cLBP), frequently attributed to lumbar disk herniation (LDH), imposes substantial limitations on daily activities. Despite its prevalence, the neural mechanisms underlying lower back pain remain incompletely elucidated. Functional magnetic resonance imaging (fMRI) emerges as a non-invasive modality extensively employed for investigating neuroplastic changes in neuroscience. In this study, task-based and resting-state fMRI methodologies are employed to probe the central mechanisms of lower back pain. Methods: The study included 71 chronic lower back pain patients (cLBP group) due to LDH and 80 age, gender, and education-matched healthy volunteers (HC group). The subjects are mainly middle-aged and elderly individuals. Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and Japanese Orthopedic Association Scores (JOA) were recorded. Resting-state and task-based fMRI data were collected. Results/discussion: No significant differences were observed in age, gender, and education level between the two groups. In the cLBP group during task execution, there was diffuse and reduced activation observed in the primary motor cortex and supplementary motor area. Additionally, during resting states, notable changes were detected in brain regions, particularly in the frontal lobe, primary sensory area, primary motor cortex, precuneus, and caudate nucleus, accompanied by alterations in Amplitude of Low Frequency Fluctuation, Regional Homogeneity, Degree Centrality, and functional connectivity. These findings suggest that chronic lower back pain may entail reduced excitability in sensory-motor areas during tasks and heightened activity in the sensory-motor network during resting states, along with modified functional connectivity in various brain regions.

5.
Expert Rev Anti Infect Ther ; : 1-8, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38525673

RESUMO

OBJECTIVES: This study examined the effectiveness of nirmatrelvir plus ritonavir (NMV-r) and molnupiravir (MOV) in treating COVID-19 among chronic kidney disease (CKD) patients. METHODS: This retrospective cohort study, using the TriNetX research network, identified stage 3-5 CKD and end-stage kidney disease (ESKD) patients with non-hospitalized COVID-19 between 1 January 2022, and 31 May 2023. Propensity score matching (PSM) was used to compare patients on NMV-r or MOV (antiviral group) against those not receiving these treatments (control group). The primary composite outcome was the cumulative hazard ratio (HR) for all-cause hospitalization or death within the 30-day follow-up. RESULTS: After PSM, two balanced cohorts of 6,275 patients each were established. The antiviral group exhibited a lower incidence of all-cause hospitalization or mortality (5.93% vs. 9.53%; HR: 0.626; 95% CI: 0.550-0.713) than controls. Additionally, antiviral recipients were associated with a lower risk of all-cause hospitalization (HR: 0.679; 95% CI: 0.594-0.777) and mortality (HR: 0.338; 95% CI: 0.227-0.504). The beneficial effects of antiviral agents were consistent across sex, age, vaccination status, antiviral type, and CKD stage. CONCLUSION: Oral antiviral agents could be associated with lower rates of all-cause hospitalization or death among non-hospitalized COVID-19 patients with CKD.

6.
Anal Chem ; 96(9): 3802-3809, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38381523

RESUMO

Fluoride anions (F-) play a crucial role in human physiological processes. However, excessive intake of F- would affect oxygen metabolism and promote the generation of oxygen-free radicals. Hence, it is essential to develop a precise and efficient fluorescent probe for visualizing F--induced oxidative stress. In this work, we developed the first bifunctional BODIPY-based fluorescent probe dfBDP with p-tert-butyldimethylsilanolate benzyl thioether as the sensing site for the detection of F- and HClO via two distinct reactions, the self-immolative removal and the thioether oxidation, which generate the sensing products with two nonoverlap fluorescence bands: 800-1200 and 500-750 nm, respectively. The probe dfBDP displays rapid response, high specificity, and sensitivity for the detection of F- (LOD, 316.2 nM) and HClO (LOD, 33.9 nM) in vitro. Cellular imaging reveals a correlation between F--induced oxidative stress and the upregulation of HClO. Finally, probe dfBDP was employed to detect F- and HClO in mice under the stimulation of F-. The experimental results display that the level of HClO elevates in the liver of mice.


Assuntos
Compostos de Boro , Corantes Fluorescentes , Ácido Hipocloroso , Camundongos , Humanos , Animais , Ácido Hipocloroso/metabolismo , Sulfetos , Oxigênio
7.
Expert Rev Anti Infect Ther ; 22(5): 343-352, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38178687

RESUMO

OBJECTIVES: This study investigated the outcomes of underweight patients with COVID-19 and the effectiveness of antiviral agents in this population. METHODS: A retrospective cohort study using theTriNetX research network was conducted. Propensity score matching (PSM) was employed to balance the first cohort involving COVID-19 patients with underweight and normal-weight. In the second cohort, underweight patients receiving antiviral agents and untreated individuals were matched using PSM. The primary outcome was a composite of all-cause hospitalization and death during the 7-30-day follow-up period. RESULTS: After PSM, the first cohort including each group of 13,502 patients with balanced baseline characteristics were identified for comparing the outcome of patients with underweight and normal weight. The underweight group had a higher risk of the composite primary outcome than those with normal weight (hazard ratio [HR], 1.251; 95% confidence interval [CI], 1.132-1.382). The second cohort included each 884 underweight patients with and without receiving antivirals.Compared with untreated patients, those receiving antiviral treatment had a lower risk of composite primary outcomes (HR, 0.426; 95% CI, 0.278-0.653). CONCLUSION: Underweight status may be associated with a higher risk of all-cause hospitalization and death in patients with COVID-19.Among underweight patients, antiviral agents demonstrated clinically beneficial effects.

8.
Chem Res Toxicol ; 37(1): 42-56, 2024 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-38091573

RESUMO

The chemokine receptor CXCR3 is functionally pleiotropic, not only recruiting immune cells to the inflamed liver but also mediating the pathological process of cholestatic liver injury (CLI). However, the mechanism of its involvement in the CLI remains unclear. Both alpha-naphthylisothiocyanate (ANIT) and triptolide are hepatotoxicants that induce CLI by bile acid (BA) dysregulation, inflammation, and endoplasmic reticulum (ER)/oxidative stress. Through molecular docking, CXCR3 is a potential target of ANIT and triptolide. Therefore, this study aimed to investigate the role of CXCR3 in ANIT- and triptolide-induced CLI and to explore the underlying mechanisms. Wild-type mice and CXCR3-deficient mice were administered with ANIT or triptolide to compare CLI, BA profile, hepatic recruitment of IFN-γ/IL-4/IL-17+CD4+T cells, IFN-γ/IL-4/IL-17+iNKT cells and IFN-γ/IL-4+NK cells, and the expression of ER/oxidative stress pathway. The results showed that CXCR3 deficiency ameliorated ANIT- and triptolide-induced CLI. CXCR3 deficiency alleviated ANIT-induced dysregulated BA metabolism, which decreased the recruitment of IFN-γ+NK cells and IL-4+NK cells to the liver and inhibited ER stress. After triptolide administration, CXCR3 deficiency ameliorated dysregulation of BA metabolism, which reduced the migration of IL-4+iNKT cells and IL-17+iNKT cells and reduced oxidative stress through inhibition of Egr1 expression and AKT phosphorylation. Our findings suggest a detrimental role of CXCR3 in ANIT- and triptolide-induced CLI, providing a promising therapeutic target and introducing novel mechanisms for understanding cholestatic liver diseases.


Assuntos
1-Naftilisotiocianato , Colestase , Diterpenos , Fenantrenos , Animais , Camundongos , 1-Naftilisotiocianato/toxicidade , 1-Naftilisotiocianato/metabolismo , Interleucina-17/toxicidade , Interleucina-17/metabolismo , Interleucina-17/uso terapêutico , Interleucina-4/toxicidade , Interleucina-4/metabolismo , Interleucina-4/uso terapêutico , Simulação de Acoplamento Molecular , Fígado/metabolismo , Colestase/induzido quimicamente , Ácidos e Sais Biliares , Compostos de Epóxi
9.
Arch Gynecol Obstet ; 309(1): 287-293, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37755532

RESUMO

PURPOSE: The aim of this study was to investigate the efficacy and safety of early cumulus cell removal (ECCR) during human in vitro fertilization (IVF). METHODS: A retrospective analysis was performed between January 2011 and December 2019. The study enrolled 1131 couples who underwent IVF treatment with ECCR. After propensity score matching at a 1:1 ratio, 1131 couples who underwent overnight coincubation of gametes were selected. The main outcome measure was the cumulative live birth rate. Secondary outcome measures included the cumulative pregnancy rate, polyspermy rate, available embryo rate, miscarriage rate, malformation rate, time to live birth, and oocyte-to-baby rate. RESULTS: There were no significant differences found between the two groups in the polyspermy rate, available embryo rate, miscarriage rate, time to live birth, oocyte-to-baby rate, and neonatal congenital anomalies rate. The results of the study showed that ECCR was associated with a significantly higher cumulative live birth rate and cumulative pregnancy rate, along with a significantly lower fertilization rate. CONCLUSIONS: ECCR tended to confer increased cumulative live birth rate and had no negative effect on the neonatal malformation rate.


Assuntos
Aborto Espontâneo , Coeficiente de Natalidade , Gravidez , Feminino , Recém-Nascido , Humanos , Resultado da Gravidez/epidemiologia , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/etiologia , Estudos de Coortes , Estudos Retrospectivos , Células do Cúmulo , Pontuação de Propensão , Fertilização in vitro/efeitos adversos , Fertilização in vitro/métodos , Taxa de Gravidez , Nascido Vivo/epidemiologia
10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1006512

RESUMO

@#Objective    To investigate the radiomics features to distinguish invasive lung adenocarcinoma with micropapillary or solid structure. Methods    A retrospective analysis was conducted on patients who received surgeries and pathologically confirmed invasive lung adenocarcinoma in our hospital from April 2016 to August 2019. The dataset was randomly divided into a training set [including a micropapillary/solid structure positive group (positive group) and a micropapillary/solid structure negative group (negative group)] and a testing set (including a positive group and a negative group) with a ratio of 7∶3. Two radiologists drew regions of interest on preoperative high-resolution CT images to extract radiomics features. Before analysis, the intraclass correlation coefficient was used to determine the stable features, and the training set data were balanced using synthetic minority oversampling technique. After mean normalization processing, further radiomics features selection was conducted using the least absolute shrinkage and selection operator algorithm, and a 5-fold cross validation was performed. Receiver operating characteristic (ROC) curves were depicted on the training and testing sets to evaluate the diagnostic performance of the radiomics model. Results    A total of 340 patients were enrolled, including 178 males and 162 females with an average age of 60.31±6.69 years. There were 238 patients in the training set, including 120 patients in the positive group and 118 patients in the negative group. There were 102 patients in the testing set, including 52 patients in the positive group and 50 patients in the negative group. The radiomics model contained 107 features, with the final 2 features selected for the radiomics model, that is, Original_ glszm_ SizeZoneNonUniformityNormalized and Original_ shape_ SurfaceVolumeRatio. The areas under the ROC curve of the training and the testing sets of the radiomics model were 0.863 (95%CI 0.815-0.912) and 0.857 (95%CI 0.783-0.932), respectively. The sensitivity was 91.7% and 73.7%, the specificity was 78.8% and 84.0%, and the accuracy was 85.3% and 78.4%, respectively. Conclusion    There are differences in radiomics features between invasive pulmonary adenocarcinoma with or without micropapillary and solid structures, and the radiomics model is demonstrated to be with good diagnostic value.

11.
Eur J Nutr ; 63(2): 613-622, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38112761

RESUMO

OBJECTIVES: This study aimed to investigate the association between vitamin D deficiency (VDD) and post-acute outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: This retrospective study used the TriNetX research network to identify COVID-19 patients between January 1 and November 30, 2022. Patients were matched using propensity score matching (PSM) and divided into VDD (< 20 ng/mL) and control (≥ 20 ng/mL) groups. The primary outcome was a composite of post-COVID-19 condition (identified by ICD-10 code), all-cause emergency department (ED) visits, hospitalization, and death during the follow-up period (90-180 days) after the diagnosis of COVID-19. RESULTS: From an initial recruitment of 42,674 non-hospitalized patients with COVID-19 and known 25(OH)D status, a VDD group of 8300 was identified and propensity matched with 8300 controls. During the follow-up period, the VDD group had a higher risk of the primary outcome than did the control group [hazard ratio (HR) = 1.122; 95% confidence interval (CI) = 1.041-1.210]. The VDD group also had a higher risk of all-cause ED visits (HR = 1.114; 95% CI = 1.012-1.226), all-cause hospitalization (HR = 1.230; 95% CI = 1.105-1.369), and all-cause death (HR = 1.748; 95% CI = 1.047-2.290) but not post-COVID-19 condition (HR = 0.980; 95% CI = 0.630-1.523), individually. CONCLUSION: Among the COVID-19 patients, VDD might be associated with a higher risk of all-cause ED visits, hospitalization, and death during the post-acute phase.


Assuntos
COVID-19 , Deficiência de Vitamina D , Humanos , COVID-19/complicações , COVID-19/epidemiologia , SARS-CoV-2 , Estudos Retrospectivos , Visitas ao Pronto Socorro , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia , Vitamina D
12.
J Med Virol ; 95(11): e29246, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-38010833

RESUMO

The effect of anemia on the post-acute outcome of patients with severe acute respiratory syndrome coronavirus 2 infection was unclear. This study aimed to investigate the potential association between nutritional deficiency anemia (NDA) status and post-acute sequelae of patients with SARS-CoV-2 infection. This retrospective cohort study included patients with coronavirus disease (COVID-19) from January 1, 2022 to November 30, 2022 using the TriNetX research network. The patients were grouped into the NDA group comprising patients diagnosed with NDA and the control group comprising patients without NDA, and propensity score matching (PSM) was performed to balance the two groups. The primary outcome was a composite of post-COVID-19 condition, all-cause hospitalization, and all-cause death. The secondary outcomes were any individual outcomes of the primary composite. The follow-up period was set at 90-180 days after COVID-19 diagnosis. Two cohorts comprising 15 446 nonhospitalized patients with COVID-19 in each group with balanced baseline characteristics were created using PSM. During the follow-up period, the NDA group demonstrated a higher risk of the composite primary outcome, including post-COVID-19 condition, all-cause hospitalization, or all-cause death (hazard ratio [HR], 1.896; 95% confidence interval [CI] = 1.757-2.045). Regarding secondary outcomes, the NDA group was associated with worse outcomes, including post-COVID-19 condition (HR, 1.992; 95% CI = 1.403-2.828), all-cause hospitalization (HR, 1.856; 95% CI = 1.714-2.009), and all-cause death (HR, 3.922; 95% CI = 2.910-5.285) compared to the control group. Among nonhospitalized patients with COVID-19, NDA was associated with a higher risk of post-COVID-19 condition, all-cause hospitalization, and all-cause death during the 90-180-day follow-up period.


Assuntos
Anemia , COVID-19 , Desnutrição , Humanos , Estudos Retrospectivos , COVID-19/complicações , Teste para COVID-19 , SARS-CoV-2 , Anemia/epidemiologia , Anemia/etiologia , Progressão da Doença
13.
Food Res Int ; 174(Pt 1): 113650, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37986488

RESUMO

To investigate the colonization and impact of the specific Lactiplantibacillus plantarum strains, four isolated strains were applied in pickled Suancai which is a traditional pickled mustard (Brassica juncea). Results showed that strain-8 with the highest lactic acid bacteria (LAB) counts and acetic acid (p < 0.05). There were 11.42 % ∼ 32.35 % differential volatile compounds detected, although nitriles, esters, and acids were predominant. L. plantarum disturbed the microbial community, in which the microbial composition of strain-11 was most similar to the naturally fermented sample. Amino acids, carbohydrate metabolism, and metabolism of cofactors and vitamins were the main functional classes because of the similar dominant microbes (Lactiplantibacillus and Levilactobacillus). The functional units were separated based on NMDS analysis, in which bacterial chemotaxis, amino acid-related units, biotin metabolism, fatty acid biosynthesis, and citrate cycle were significantly different calculated by metagenomeSeq and Benjamin-Hochberg methods (p < 0.05). The contents of most flavor compounds were consistent with their corresponding enzymes. In particular, glucosinolates metabolites were different and significantly related to the myrosinase and metabolic preference of LAB. Therefore, this study revealed the impact mechanism of the specific L. plantarum strains and provided a perspective for developing microbial resources to improve the flavor diversity of fermented vegetables.


Assuntos
Lactobacillales , Verduras , Ácido Acético , Aminoácidos , Citratos
14.
Chem Commun (Camb) ; 59(85): 12775-12778, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37814891

RESUMO

A dual functional BODIPY fluorescent probe was developed for simultaneous detection of H2O2 and viscosity, by collecting fluorescence from 800-1100 nm and 550-750 nm, respectively. Bioimaging based on the probe shows that H2O2 accumulates and cytoplasmic viscosity increases during the palmitic acid (PA)-induced pyroptosis process.


Assuntos
Corantes Fluorescentes , Peróxido de Hidrogênio , Humanos , Viscosidade , Piroptose , Células HeLa
16.
Bioengineering (Basel) ; 10(10)2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37892869

RESUMO

(1) Background: Persistent hyperglycemia in diabetes mellitus (DM) increases the risk of death and causes cardiovascular disease (CVD), resulting in significant social and economic costs. This study used a machine learning (ML) technique to build prediction models with the factors of lifestyle, medication compliance, and self-control in eating habits and then implemented a predictive system based on the best model to forecast whether blood glucose can be well-controlled within 1 year in diabetic patients attending a DM nutritional clinic. (2) Methods: Data were collected from outpatients aged 20 years or older with type 2 DM who received nutrition education in Chi Mei Medical Center. Multiple ML algorithms were used to build the predictive models. (3) Results: The predictive models achieved accuracies ranging from 0.611 to 0.690. The XGBoost model with the highest area under the curve (AUC) of 0.738 was regarded as the best and used for the predictive system implementation. SHAP analysis was performed to interpret the feature importance in the best model. The predictive system, evaluated by dietitians, received positive feedback as a beneficial tool for diabetes nutrition consultations. (4) Conclusions: The ML prediction model provides a promising approach for diabetes nutrition consultations to maintain good long-term blood glucose control, reduce diabetes-related complications, and enhance the quality of medical care.

17.
Int J Antimicrob Agents ; 62(6): 106984, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37769748

RESUMO

OBJECTIVE: To investigate the association between nirmatrelvir plus ritonavir (NMV-r) and the outcomes of non-hospitalized obese patients with coronavirus disease 2019 (COVID-19). METHODS: This retrospective cohort study used the TriNetX research network to identify non-hospitalized obese adult patients with COVID-19 between 1 January 2022 and 30 June 2023. Propensity score matching was used to match patients receiving NMV-r (NMV-r group) with those not receiving NMV-r (control group). The primary outcome was the compositive outcome of all-cause emergency department (ED) visits, hospitalization or death during the 30-day follow-up period. RESULTS: Using propensity score matching methods, two cohorts of 30,969 patients each with balanced baseline characteristics were identified. During the follow-up period, the NMV-r group had a lower risk of all-cause ED visits, hospitalization or death [4.80% (n=1489) vs 5.50% (n=1705); hazard ratio (HR) 0.900, 95% confidence interval (CI) 0.839-0.965]. Compared with the control group, the NMV-r group had a lower risk of all-cause ED visits (HR 0.812, 95% CI 0.740-0.891) and all-cause mortality (HR 0.089, 95% CI 0.027-0.288). The lower risk in the NMV-r group compared with the control group was observed consistently in most subgroup analyses according to body mass index (30.0-34.9 kg/m2: HR 0.68, 95% CI 0.55-0.82; 35.0-39.9 kg/m2: HR 0.67, 95% CI 0.52-0.87), age (4-64 years: HR 0.83, 95% CI 0.75-0.92; ≥65 years: HR 0.88, 95% CI 0.79-0.98), sex (men: HR 0.69, 95% CI 0.60-0.79; women: HR 0.69, 95% CI 0.63-0.76) and vaccination status (unvaccinated: HR 0.75, 95% CI 0.70-0.81). CONCLUSION: NMV-r is associated with reduced risk of all-cause ED visits, hospitalization and death for non-hospitalized obese patients with COVID-19. Accordingly, these findings support the use of NMV-r in obese patients.


Assuntos
COVID-19 , Adulto , Masculino , Humanos , Feminino , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Estudos Retrospectivos , Ritonavir/uso terapêutico , Tratamento Farmacológico da COVID-19 , Obesidade/complicações , Antivirais/uso terapêutico
18.
Transl Oncol ; 38: 101785, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37713975

RESUMO

BACKGROUND: Nasopharyngeal carcinoma (NPC) is associated with Epstein-Barr virus (EBV) infection. To test preclinical NPC drugs, we established two patient-derived xenograft (PDX) mouse models, EBV-positive PDX-B13 and EBV-negative PDX-Li41, for drug screening. METHODS: Based on next generation sequencing (NGS) studies, PDX-B13 had CCND1 copy number (CN) gain but CDKN2A CN loss, whereas PDX-Li41 had CDKN2A and RB1 CN loss, TSC1 (negative regulator of mTOR) frameshift deletion mutation, and increased activation of mTOR, a serine/threonine kinase that governs metabolism, autophagy, and apoptosis. Increased mTOR was also associated with poor NPC prognosis. RESULTS: Everolimus, an mTOR inhibitor, suppressed tumor growth in the two PDX NPC models and had an additive antitumor effect with palbociclib, a CDK4/6 inhibitor. PDX tumors treated with various drugs or untreated were subjected to RNA sequencing, transcriptome profile analysis, and selective Western blotting to understand the interactions between these drugs and gene expression profiles. Palbociclib also suppressed EB viral nuclear antigen (EBNA1) expression in PDX-B13. Everolimus together with autophagy inhibitor, hydroxychloroquine, had additive anti-tumor effect on PDX-B13 tumor. Immunohistochemistry revealed that high mTOR levels were correlated with poor overall survival in patients with metastatic NPC (N = 90). CONCLUSIONS: High mTOR levels are a poor prognostic factor in NPC, and cell cycle, mTOR and autophagy pathways may serve as therapeutic targets in NPC. In addition, PDX models can be used for efficiently testing potential NPC drugs.

19.
Altern Ther Health Med ; 29(8): 624-630, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37678866

RESUMO

Objective: To develop a multi-component exercise training program for elderly patients with chronic obstructive pulmonary disease (COPD) and skeletal muscle dysfunction (SMD), and to explore its application value. Methods: This study involved 68 elderly patients with both COPD and SMD who were hospitalized at The First Affiliated Hospital of Hainan Medical College from September 2019 to August 2021. They were randomly divided into an intervention group and a control group. The intervention group received a 12-month multi-component exercise training program, while the control group received routine intervention. We compared skeletal muscle function, strength, lung function, and oxygen saturation between the groups before and at 3, 6, and 12 months after the intervention. The patient's daily living activities and dyspnea severity were assessed using the Modified Barthel Index (MBI) and the modified British Medical Research Council (mMRC) dyspnea scale. Flow cytometry was used to determine changes in the proportion of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells, and the CD3+CD4+/CD3+CD8+ ratio in the patients' lymphocytes before and after the intervention. Results: The six-minute walk distance of the intervention group at 6 and 12 months after the intervention was longer than that of the control group. The peak torque of elbow flexion and extension and knee flexion and extension muscles of the intervention group at 12 months after intervention was higher than that of the control group (P < .05). The forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC of the intervention group at 6 and 12 months after intervention were higher than those of the control group. The oxygen saturation (SaO2) and partial pressure of oxygen (PaO2) of the intervention group at 6 and 12 months after the intervention were higher than those of the control group (P < .05). The MBI and mMRC scores of the intervention group at 6 and 12 months after intervention were higher than those of the control group (P < .05). The indexes of T lymphocyte immune function, CD3+T cells, CD3+CD4+T cells, and the ratio of CD3+CD4+/CD3+CD8+ in the intervention group were also higher than those in the control group at 3, 6, and 12 months (P < .05). Conclusion: Multi-component exercise training program intervention can effectively improve skeletal muscle function and lung function in elderly COPD patients with SMD, reduce the degree of hypoxia and dyspnea, and improve patients' daily living activities and immune function recovery.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Humanos , Idoso , Doença Pulmonar Obstrutiva Crônica/terapia , Volume Expiratório Forçado , Dispneia , Caminhada , Músculo Esquelético
20.
Ann Clin Lab Sci ; 53(4): 516-528, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37625828

RESUMO

OBJECTIVE: This study aimed to explore the expression of the C-type lectin domain family 4 member G (CLEC4G) gene in the liver sinusoidal endothelial cells (LSECs) during liver pathogenesis, and to evaluate its correlation with CD34 and clinical significance in hepatocellular carcinoma patients. METHODS: We conducted bioinformatics analysis of the differential expression of CLEC4G in various human organs, carcinomatous and adjacent tissues. Then, mRNA and protein expression levels of CD34 in hepatocellular carcinoma (HCC) samples were detected via real-time quantitative reverse transcription PCR (qRT-PCR) and immunohistochemical (IHC), respectively. ELISA was applied to detect serum levels of CLEC4G in healthy controls, liver fibrosis and HCC patients. RESULTS: The expressions of mRNA and protein levels of CLEC4G were higher in normal liver tissues, moderately expressed in cirrhotic and para-cancerous tissues (P<0.001), and lowest in HCC tissues (P<0.001). We also found high CD34 expression in tumors, which was negatively correlated with CLEC4G at both mRNA and protein levels. Compared to the healthy controls, the CLEC4G levels in liver fibrosis patients and HCC patients gradually became lower (P<0.001). CONCLUSIONS: The low expression of CLEC4G is potentially correlated with LSEC capillarization and the appearance of micro-vessels. Such a phenomenon may serve as a reliable diagnostic marker for hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Antígenos CD34/genética , Carcinoma Hepatocelular/genética , Moléculas de Adesão Celular , Células Endoteliais , Lectinas Tipo C/genética , Cirrose Hepática/genética , Neoplasias Hepáticas/genética
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