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1.
Cancer Biol Med ; 21(6)2024 May 31.
Article de Anglais | MEDLINE | ID: mdl-38825813

RÉSUMÉ

In exploring persistent infections and malignancies, a distinctive subgroup of CD8+ T cells, progenitor exhausted CD8+ T (Tpex) cells, has been identified. These Tpex cells are notable for their remarkable self-renewal and rapid proliferation abilities. Recent strides in immunotherapy have demonstrated that Tpex cells expand and differentiate into responsive exhausted CD8+ T cells, thus underscoring their critical role in the immunotherapeutic retort. Clinical examinations have further clarified a robust positive correlation between the proportional abundance of Tpex cells and enhanced clinical prognosis. Tpex cells have found noteworthy applications in the formulation of inventive immunotherapeutic approaches against tumors. This review describes the functions of Tpex cells in the tumor milieu, particularly their potential utility in tumor immunotherapy. Precisely directing Tpex cells may be essential to achieving successful outcomes in immunotherapy against tumors.


Sujet(s)
Lymphocytes T CD8+ , Immunothérapie , Tumeurs , Humains , Tumeurs/thérapie , Tumeurs/immunologie , Immunothérapie/méthodes , Lymphocytes T CD8+/immunologie , Animaux , Microenvironnement tumoral/immunologie
2.
Apoptosis ; 2024 Jun 09.
Article de Anglais | MEDLINE | ID: mdl-38853202

RÉSUMÉ

Ovarian cancer is a malignant tumor originating from the ovary, characterized by its high mortality rate and propensity for recurrence. In some patients, especially those with recurrent cancer, conventional treatments such as surgical resection or standard chemotherapy yield suboptimal results. Consequently, there is an urgent need for novel anti-cancer therapeutic strategies. Ferroptosis is a distinct form of cell death separate from apoptosis. Ferroptosis inducers have demonstrated promising potential in the treatment of ovarian cancer, with evidence indicating their ability to enhance ovarian cancer cell sensitivity to cisplatin. However, resistance of cancer cells to ferroptosis still remains an inevitable challenge. Here, we analyzed genome-scale CRISPR-Cas9 loss-of function screens and identified PAX8 as a ferroptosis resistance protein in ovarian cancer. We identified PAX8 as a susceptibility gene in GPX4-dependent ovarian cancer. Depletion of PAX8 rendered GPX4-dependent ovarian cancer cells significantly more sensitive to GPX4 inhibitors. Additionally, we found that PAX8 inhibited ferroptosis in ovarian cancer cells. Combined treatment with a PAX8 inhibitor and RSL3 suppressed ovarian cancer cell growth, induced ferroptosis, and was validated in a xenograft mouse model. Further exploration of the molecular mechanisms underlying PAX8 inhibition of ferroptosis mutations revealed upregulation of glutamate-cysteine ligase catalytic subunit (GCLC) expression. GCLC mediated the ferroptosis resistance induced by PAX8 in ovarian cancer. In conclusion, our study underscores the pivotal role of PAX8 as a therapeutic target in GPX4-dependent ovarian cancer. The combination of PAX8 inhibitors such as losartan and captopril with ferroptosis inducers represents a promising new approach for ovarian cancer therapy.

3.
Ophthalmol Retina ; 2024 Jun 13.
Article de Anglais | MEDLINE | ID: mdl-38878897

RÉSUMÉ

PURPOSE: To investigate the relationships between contrast sensitivity (CS), choriocapillaris perfusion and other structural optical coherence tomography (OCT) biomarkers in dry age-related macular degeneration (AMD). DESIGN: Cross-sectional, observational study. PARTICIPANTS: One hundred AMD eyes (22 early, 52 intermediate and 26 late) from 74 patients and 45 control eyes from 37 age-similar subjects. METHODS: All participants had visual acuity (VA) assessment, quantitative contrast sensitivity function (qCSF) testing, macular OCT, and 6x6-mm swept-source OCT angiography (OCTA) scans on the same day. OCT volumes were analyzed for subretinal drusenoid deposits and hyporeflective drusen cores, and to measure thickness of the outer nuclear layer (ONL). OCTA scans were utilized to calculate drusen volume, inner choroid flow deficit percentage (IC-FD%), and to measure the area of choroidal hypertransmission defects (HTD). IC-FD% was measured from a 16 µm-thick choriocapillaris slab after compensation and binarization with Phansalkar's method. Generalized linear mixed-effects models were used to evaluate the associations between functional and structural variables. MAIN OUTCOME MEASURES: To explore the associations between qCSF-measured CS, ICFD% and various AMD imaging biomarkers. RESULTS: AMD exhibited significantly reduced qCSF metrics eyes across all stages compared to controls. Univariate analysis revealed significant associations between various imaging biomarkers, reduced qCSF metrics and VA in both groups. Multivariate analysis confirmed that higher IC-FD% in the central 5 mm was significantly associated with decreases in all qCSF metrics in AMD eyes (ß= -0.74 to -0.25, all p<0.05), but not with VA (p>0.05). ONL thickness in the central 3 mm correlated with both VA (ß= 2.85, p<0.001) and several qCSF metrics (ß= 0.01-0.90, all p<0.05), especially in AMD eyes. Further, larger HTD areas were associated with decreased VA (ß=-0.89, p<0.001) and reduced CS at low-intermediate frequencies across AMD stages (ß= -0.30 to -0.29, p<0.001). CONCLUSIONS: The significant association between IC-FD% in the central 5 mm and qCSF-measured CS reinforces the hypothesis that decreased macular choriocapillaris perfusion contributes to visual function changes in AMD, which are more pronounced in CS than in VA.

4.
Prehosp Disaster Med ; : 1-9, 2024 May 07.
Article de Anglais | MEDLINE | ID: mdl-38712485

RÉSUMÉ

INTRODUCTION: Medical resuscitations in rugged prehospital settings require emergency personnel to perform high-risk procedures in low-resource conditions. Just-in-Time Guidance (JITG) utilizing augmented reality (AR) guidance may be a solution. There is little literature on the utility of AR-mediated JITG tools for facilitating the performance of emergent field care. STUDY OBJECTIVE: The objective of this study was to investigate the feasibility and efficacy of a novel AR-mediated JITG tool for emergency field procedures. METHODS: Emergency medical technician-basic (EMT-B) and paramedic cohorts were randomized to either video training (control) or JITG-AR guidance (intervention) groups for performing bag-valve-mask (BVM) ventilation, intraosseous (IO) line placement, and needle-decompression (Needle-d) in a medium-fidelity simulation environment. For the interventional condition, subjects used an AR technology platform to perform the tasks. The primary outcome was participant task performance; the secondary outcomes were participant-reported acceptability. Participant task score, task time, and acceptability ratings were reported descriptively and compared between the control and intervention groups using chi-square analysis for binary variables and unpaired t-testing for continuous variables. RESULTS: Sixty participants were enrolled (mean age 34.8 years; 72% male). In the EMT-B cohort, there was no difference in average task performance score between the control and JITG groups for the BVM and IO tasks; however, the control group had higher performance scores for the Needle-d task (mean score difference 22%; P = .01). In the paramedic cohort, there was no difference in performance scores between the control and JITG group for the BVM and Needle-d tasks, but the control group had higher task scores for the IO task (mean score difference 23%; P = .01). For all task and participant types, the control group performed tasks more quickly than in the JITG group. There was no difference in participant usability or usefulness ratings between the JITG or control conditions for any of the tasks, although paramedics reported they were less likely to use the JITG equipment again (mean difference 1.96 rating points; P = .02). CONCLUSIONS: This study demonstrated preliminary evidence that AR-mediated guidance for emergency medical procedures is feasible and acceptable. These observations, coupled with AR's promise for real-time interaction and on-going technological advancements, suggest the potential for this modality in training and practice that justifies future investigation.

5.
Atherosclerosis ; 392: 117527, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38583286

RÉSUMÉ

BACKGROUND AND AIMS: Diabetic atherosclerotic vascular disease is characterized by extensive vascular calcification. However, an elevated blood glucose level alone does not explain this pathogenesis. We investigated the metabolic markers underlying diabetic atherosclerosis and whether extracellular Hsp90α (eHsp90α) triggers vascular endothelial calcification in this particular metabolic environment. METHODS: A parallel human/animal model metabolomics approach was used. We analyzed 40 serum samples collected from 24 patients with atherosclerosis and from the STZ-induced ApoE-/- mouse model. A multivariate statistical analysis of the data was performed, and mouse aortic tissue was collected for the assessment of plaque formation. In vitro, the effects of eHsp90α on endothelial cell calcification were assessed by serum analysis, Western blotting and immunoelectron microscopy. RESULTS: Diabetic ApoE-/- mice showed more severe plaque lesions and calcification damage. Stearamide, oleamide, l-thyroxine, l-homocitrulline and l-citrulline are biomarkers of diabetic ASVD; l-thyroxine was downregulated in both groups, and the thyroid sensitivity index was correlated with serum Hsp90α concentration. In vitro studies showed that eHsp90α increased Runx2 expression in endothelial cells through the LRP1 receptor. l-thyroxine reduced the increase in Runx2 levels caused by eHsp90α and affected the distribution and expression of LRP1 through hydrogen bonding with glutamine at position 1054 in the extracellular segment of LRP1. CONCLUSIONS: This study provides a mechanistic link between characteristic serum metabolites and diabetic atherosclerosis and thus offers new insight into the role of extracellular Hsp90α in promoting vascular calcification.


Sujet(s)
Diabète expérimental , Protéines du choc thermique HSP90 , Souris invalidées pour les gènes ApoE , Plaque d'athérosclérose , Thyroxine , Calcification vasculaire , Humains , Animaux , Protéines du choc thermique HSP90/métabolisme , Calcification vasculaire/métabolisme , Calcification vasculaire/anatomopathologie , Mâle , Diabète expérimental/traitement médicamenteux , Diabète expérimental/complications , Thyroxine/sang , Femelle , Protéine-1 apparentée au récepteur des LDL/métabolisme , Adulte d'âge moyen , Sous-unité alpha 1 du facteur CBF/métabolisme , Souris , Athérosclérose/métabolisme , Athérosclérose/anatomopathologie , Angiopathies diabétiques/métabolisme , Angiopathies diabétiques/anatomopathologie , Angiopathies diabétiques/étiologie , Métabolomique/méthodes , Cellules endothéliales/métabolisme , Cellules endothéliales/effets des médicaments et des substances chimiques , Métabolome/effets des médicaments et des substances chimiques , Sujet âgé , Souris de lignée C57BL , Maladies de l'aorte/métabolisme , Maladies de l'aorte/anatomopathologie , Maladies de l'aorte/sang , Marqueurs biologiques/sang , Cellules endothéliales de la veine ombilicale humaine/métabolisme
6.
Transfus Clin Biol ; 2024 Apr 25.
Article de Anglais | MEDLINE | ID: mdl-38670448

RÉSUMÉ

BACKGROUND: An adequate blood supply is an important guarantee for saving lives and protecting health. In order to manage the blood supply more effectively when the condition of demand and supply are uncertainty, it is very important to forecast the demands of blood resources. MATERIALS AND METHODS: SARIMAX model and LSTM model were integrated into the prediction system of blood station. The collection and supply data of blood components was directly imported into the forecasting models to achieve automatic data update and model update. The forecasting daily demands of apheresis platelets, washing red blood cells (RBCs), suspended RBCs and plasma were recorded from January to June 2023 and compared with real data. RESULTS: The prediction models had good forecasting performances. In the goodness of fit results of apheresis platelet model, the maximum value of coefficient of determination (R2) could reach 87.6%, and the minimum value of the mean absolute percentage error (MAPE) was only 0.0037. The predicted data of washing RBCs could be basically fitted, and the MAPE was 0.0121. For the prediction of suspended RBCs, the R2 was greater than 66%, and the MAPE could be 0.0372. The plasma model generated very high goodness of fit results, with R2 of over 90% and the lowest MAPE of 0.0394. CONCLUSION: The forecasting models, which predicts future demands of different blood components based on historical data, can help managers to overcome the challenges of blood stock control more effectively, thereby reducing blood waste and blood shortages.

7.
PLoS Genet ; 20(4): e1011235, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38648200

RÉSUMÉ

Tumor-associated macrophages (TAM) subtypes have been shown to impact cancer prognosis and resistance to immunotherapy. However, there is still a lack of systematic investigation into their molecular characteristics and clinical relevance in different cancer types. Single-cell RNA sequencing data from three different tumor types were used to cluster and type macrophages. Functional analysis and communication of TAM subpopulations were performed by Gene Ontology-Biological Process and CellChat respectively. Differential expression of characteristic genes in subpopulations was calculated using zscore as well as edgeR and Wilcoxon rank sum tests, and subsequently gene enrichment analysis of characteristic genes and anti-PD-1 resistance was performed by the REACTOME database. We revealed the heterogeneity of TAM, and identified eleven subtypes and their impact on prognosis. These subtypes expressed different molecular functions respectively, such as being involved in T cell activation, apoptosis and differentiation, or regulating viral bioprocesses or responses to viruses. The SPP1 pathway was identified as a critical mediator of communication between TAM subpopulations, as well as between TAM and epithelial cells. Macrophages with high expression of SPP1 resulted in poorer survival. By in vitro study, we showed SPP1 mediated the interactions between TAM clusters and between TAM and tumor cells. SPP1 promoted the tumor-promoting ability of TAM, and increased PDL1 expression and stemness of tumor cells. Inhibition of SPP1 attenuated N-cadherin and ß-catenin expression and the activation of AKT and STAT3 pathway in tumor cells. Additionally, we found that several subpopulations could decrease the sensitivity of anti-PD-1 therapy in melanoma. SPP1 signal was a critical pathway of communication between macrophage subtypes. Some specific macrophage subtypes were associated with immunotherapy resistance and prognosis in some cancer types.


Sujet(s)
Tumeurs , Ostéopontine , Macrophages associés aux tumeurs , Humains , Macrophages associés aux tumeurs/immunologie , Macrophages associés aux tumeurs/métabolisme , Pronostic , Tumeurs/immunologie , Tumeurs/génétique , Ostéopontine/génétique , Ostéopontine/métabolisme , Régulation de l'expression des gènes tumoraux , Facteur de transcription STAT-3/génétique , Facteur de transcription STAT-3/métabolisme , Lignée cellulaire tumorale , bêta-Caténine/génétique , bêta-Caténine/métabolisme , Analyse sur cellule unique , Transduction du signal , Macrophages/immunologie , Macrophages/métabolisme , Communication cellulaire/immunologie
8.
Asian J Pharm Sci ; 19(1): 100888, 2024 Feb.
Article de Anglais | MEDLINE | ID: mdl-38434719

RÉSUMÉ

Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy, but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration. Herein, we designed a cancer-associated fibroblasts (CAFs) triggered structure-transformable nano-assembly (HSD-P@V), which can directionally deliver valsartan (Val, CAFs regulator) and doxorubicin (DOX, senescence inducer) to the specific targets. In detail, DOX is conjugated with hyaluronic acid (HA) via diselenide bonds (Se-Se) to form HSD micelles, while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer, which is coated on Val nanocrystals (VNs) surface for improving the stability and achieving responsive release. Once arriving at tumor microenvironment and touching CAFs, HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment. VNs can degrade the extracellular matrix, leading to the enhanced penetration of HSD. HSD targets tumor cells, releases DOX to induce senescence, and recruits effector immune cells. Furthermore, senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy. In vitro and in vivo results show that the nano-assembly remarkably inhibits tumor growth as well as lung metastasis, and extends tumor-bearing mice survival. This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.

10.
Ophthalmic Surg Lasers Imaging Retina ; 55(4): 212-219, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38319059

RÉSUMÉ

BACKGROUND AND OBJECTIVE: We sought to establish normative quantitative contrast sensitivity function (qCSF) values in healthy adult eyes and investigate the effect of age on qCSF. PATIENTS AND METHODS: Healthy eyes underwent qCSF testing (adaptive sensory technology) and Snellen's visual acuity (VA). Descriptive statistics and mixed-effects multivariable linear regressions were evaluated. RESULTS: A total of 334 eyes (290 patients) with median age 61 years (range 21 to 88) had qCSF values as follows: area under the log contrast sensitivity function curve: 1.18; contrast acuity: 1.32; contrast sensitivity (CS) at 1 cycle per degree (cpd): 1.32; CS at 1.5 cpd: 1.37; CS at 3 cpd: 1.38; CS at 6 cpd: 1.20; CS at 12 cpd: 0.69; CS at 18 cpd: 0.22. Linear reductions in qCSF values per decade of age ranged from -0.02 to -0.07 vs 0.01 for visual acuity (VA). Age had a greater effect on the majority of qCSF values than VA (beta standardized regression coefficient ranged from -0.309 to -0.141 for qCSF values vs 0.177 for VA). CONCLUSIONS: We herein establish a normative database for qCSF and quantify the effect of age on qCSF values, adding evidence towards the validation of qCSF as a clinical endpoint. [Ophthalmic Surg Lasers Imaging Retina 2024;55:212-219.].


Sujet(s)
Vieillissement , Sensibilité au contraste , Acuité visuelle , Humains , Sensibilité au contraste/physiologie , Adulte , Femelle , Mâle , Adulte d'âge moyen , Acuité visuelle/physiologie , Sujet âgé , Jeune adulte , Sujet âgé de 80 ans ou plus , Vieillissement/physiologie , Volontaires sains , Valeurs de référence , Bases de données factuelles
11.
Inflammation ; 2024 Feb 27.
Article de Anglais | MEDLINE | ID: mdl-38411775

RÉSUMÉ

Retinal inflammation is a pivotal characteristic observed in various retinal degenerative disorders, notably age-related macular degeneration (AMD), primarily orchestrated by the activation of microglia. Targeting the inhibition of microglial activation has emerged as a therapeutic focal point. Quercetin (Qu), ubiquitously present in dietary sources and tea, has garnered attention for its anti-neuroinflammatory properties. However, the impact of Qu on retinal inflammation and the associated mechanistic pathways remains incompletely elucidated. In this study, retinal inflammation was induced in adult male C57BL/6 J mice through intraperitoneal administration of LPS. The results revealed that Qu pre-treatment induces a phenotypic shift in microglia from M1 phenotype to M2 phenotype. Furthermore, Qu attenuated retinal inflammation and stabilized the integrity of the blood-retina barrier (BRB). In vitro experiments revealed that Qu impedes microglial activation, proliferation, and migration, primarily via modulation the ERK/STAT3 signaling pathway. Notably, these actions of Qu significantly contributed to the preservation of photoreceptors. Consequently, Qu pre-treatment holds promise as an effective strategy for controlling retinal inflammation and preserving visual function.

12.
Clin Exp Ophthalmol ; 52(5): 558-575, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38282307

RÉSUMÉ

BACKGROUND: Circular RNAs (circRNAs) are implicated in retinal pathophysiology; however, their expression profiles and functions in photoreceptor apoptosis are largely unknown. We explored circRNA-expression profiles and circUvrag (host gene: Uvrag, ultraviolet radiation resistance associated gene) function in light-induced photoreceptor apoptosis. METHODS: Sprague-Dawley rats and 661 W photoreceptor cells were exposed to blue light to establish light-induced photoreceptor degeneration. Differentially expressed circRNAs were identified using microarrays. Potential functions of dysregulated circRNAs were analysed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. CircUvrag expression and localization were evaluated using quantitative RT-PCR and fluorescence in situ hybridization, respectively. CircUvrag overexpression and knockdown were induced using a plasmid and a small interfering RNA, respectively, and retinal function and structure were assessed using scotopic electroretinography, haematoxylin-eosin staining, and TUNEL staining. Microglial migration was assessed using IBA1 immunostaining. The apoptosis ratio of photoreceptor cells in vitro was detected using flow cytometry. RESULTS: We identified 764 differentially expressed circRNAs, which were potentially related with the development of retinal structures, including neurons, dendrites, and synapses, and might participate in nervous-system pathophysiology. Light exposure enriched circUvrag in the cytoplasm of photoreceptors in the outer nuclear layer (ONL). CircUvrag knockdown decreased photoreceptor apoptosis and microglial migration to the ONL after light exposure, preserving ONL thickness and a-wave amplitude. In vitro, circUvrag knockdown inhibited photoreceptor apoptosis, although circUvrag overexpression slightly promoted photoreceptor apoptosis. CONCLUSIONS: CircUvrag knockdown attenuated light-induced photoreceptor apoptosis, and might be a potential target in retinal degeneration.


Sujet(s)
Apoptose , Lumière , Cellules photoréceptrices de vertébré , ARN circulaire , ARN , Rat Sprague-Dawley , Dégénérescence de la rétine , Animaux , ARN circulaire/génétique , Dégénérescence de la rétine/génétique , Dégénérescence de la rétine/métabolisme , Dégénérescence de la rétine/étiologie , Dégénérescence de la rétine/physiopathologie , Rats , Cellules photoréceptrices de vertébré/anatomopathologie , Cellules photoréceptrices de vertébré/métabolisme , Lumière/effets indésirables , ARN/génétique , Hybridation fluorescente in situ , Régulation de l'expression des gènes , Modèles animaux de maladie humaine , Électrorétinographie , Lésions radiques expérimentales/génétique , Lésions radiques expérimentales/métabolisme , Réaction de polymérisation en chaine en temps réel , Analyse de profil d'expression de gènes , Méthode TUNEL , Mâle , Cytométrie en flux
13.
Micromachines (Basel) ; 15(1)2024 Jan 20.
Article de Anglais | MEDLINE | ID: mdl-38276852

RÉSUMÉ

Traditional ytterbium-doped high-power fiber lasers generally use a unidirectional output structure. To reduce the cost and improve the efficiency of the fiber laser, we propose a bidirectional output fiber laser (BOFL). The BOFL has many advantages over that of the traditional unidirectional output fiber laser (UOFL) and has a wide application in the industrial field. In theory, the model of the BOFL is established, and a comparison of the nonlinear effect in the traditional UOFL and the BOFL is studied. Experimentally, high-power continuous wave (CW) and quasi-continuous wave (QCW) BOFLs are demonstrated. In the continuous laser, we first combine the BOFL with the oscillating amplifying integrated structure, and a near-single-mode bidirectional 2 × 4 kW output with a total power of above 8 kW is demonstrated. Then, with the simple BOFL, a CW bidirectional 2 × 5 kW output with a total power of above 10 kW is demonstrated. By means of pump source modulation, a QCW BOFL is developed, and the output of a near-single mode QCW laser with a peak output of 2 × 4.5 kW with a total peak power of more than 9 kW is realized. Both CW and QCW output BOFL are the highest powers reported at present.

14.
Graefes Arch Clin Exp Ophthalmol ; 262(3): 813-822, 2024 Mar.
Article de Anglais | MEDLINE | ID: mdl-37955702

RÉSUMÉ

PURPOSE: The purpose of this study is to investigate test-retest reliability and agreement of the quantitative contrast sensitivity function test (qCSF) in the retina clinic. METHODS: A total of 121 right eyes of 121 patients were tested and consecutively re-tested with qCSF in the retina clinic. Outcomes included area under the logarithm of contrast sensitivity function curve (AULCSF), contrast acuity, and contrast sensitivity thresholds at 1-18 cycles per degree (cpd). Test-retest means were compared with paired t-test, variability was compared with the Brown-Forsythe test, and intraclass correlation coefficient (ICC) and Bland Altman plots evaluated reliability and agreement. RESULTS: Mean test-retest differences for all qCSF metrics ranged from 0.02 to 0.05 log units without statistically significant differences in variability. Standard deviations ranged from 0.08 to 0.14. Coefficients of repeatability ranged from 0.16 to 0.27 log units. ICC > 0.9 for all metrics except 1cpd (ICC = 0.84, all p < 0.001); AULCSF ICC = 0.971. CONCLUSION: qCSF-measured contrast sensitivity shows great test-retest repeatability and agreement in the retina clinic.


Sujet(s)
Sensibilité au contraste , Tests de vision , Humains , Reproductibilité des résultats , Rétine
15.
Endocr Pract ; 30(2): 122-127, 2024 Feb.
Article de Anglais | MEDLINE | ID: mdl-37952581

RÉSUMÉ

OBJECTIVE: People with diabetes mellitus, particularly those with limited access to longitudinal care, frequently present to the emergency department (ED). Continuous glucose monitoring (CGM) has been shown to improve outcomes in ambulatory settings, so we hypothesized that it would be beneficial if initiated upon ED discharge. METHODS: We randomized adults with diabetes who were seen in the ED for hypo- or hyperglycemia to either 14 days of flash CGM or care coordination alone. All participants were scheduled to follow up in our diabetes specialty clinic. Outcomes included clinic attendance, the 3-month change in hemoglobin A1c, and repeat ED utilization. RESULTS: We recruited 30 participants, including 13 with newly diagnosed diabetes. All but one (97%) had type 2 diabetes. We found no significant difference between the CGM (n = 16) and control (n = 14) groups in terms of clinic attendance (75 vs 64%, P = .61) or repeat ED utilization (31 vs 50%, P = .35), although our power was low. The absolute reduction in A1c was greater in the CGM group (5.2 vs 2.4%, P = .08). Among newly diagnosed participants for whom we had data, 7 out of 7 in the CGM group had a follow-up A1c under 7% compared to 1 out of 3 in the control group (P = .03). Over 90% of patients and providers found the CGM useful. CONCLUSIONS: Our data demonstrate the feasibility of starting CGM in the ED, a valuable setting for engaging difficult-to-reach patients. Our pilot study was limited by its small sample size, however, as recruitment in the ED can be challenging.


Sujet(s)
Diabète de type 1 , Diabète de type 2 , Hypoglycémie , Adulte , Humains , Glycémie , Hémoglobine glyquée , Hypoglycémiants , Hypoglycémie/diagnostic , Projets pilotes , Diabète de type 2/thérapie , Autosurveillance glycémique , , Sortie du patient
16.
Acta Pharm Sin B ; 13(12): 5091-5106, 2023 Dec.
Article de Anglais | MEDLINE | ID: mdl-38045037

RÉSUMÉ

Despite exciting achievements with some malignancies, immunotherapy for hypoimmunogenic cancers, especially glioblastoma (GBM), remains a formidable clinical challenge. Poor immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune response. Herein, we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the "danger" signal of GBM. We demonstrated the feasibility of this strategy in two scenarios of GBM. In the first scenario, we showed that this simultaneous amplification system, in conjunction with local chemotherapy, enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model; thus, ultimately making a cold GBM hot and suppressing postoperative relapse. Encouraged by excellent efficacy, we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM, a disease with limited clinical treatment options. In general, this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractory malignancies.

17.
Sci Rep ; 13(1): 21218, 2023 Dec 01.
Article de Anglais | MEDLINE | ID: mdl-38040833

RÉSUMÉ

Quasi-continuous wave (QCW) laser has a very broad application in the industrial field, especially in additive manufacturing, surface treatment, laser cutting, laser cleaning, and laser drilling. Compared with the unidirectional fiber laser, the bidirectional output can be achieved two ports high power output with only one resonator, which can greatly reduce the industrial cost. However, there are few researches on QCW fiber lasers with bidirectional output. Here, we optimized and demonstrated a bidirectional output QCW laser with output power of 2 × 4.5 kW based on a double-clad ytterbium-doped fiber with a core/cladding diameter of 25/400 µm. The peak power at both ends reached 4515 W and 4694 W, respectively. The Raman suppression ratio at both ends of A and B is about 12 dB, and the beam quality factor M2 is about 1.37 and 1.42, respectively. The corresponding optical-to-optical efficiency is 79%. To the best of our knowledge, this is the highest peak power of QCW laser with near-single-mode beam quality in a bidirectional structure laser.

18.
Int Wound J ; 21(3): e14476, 2023 Nov 01.
Article de Anglais | MEDLINE | ID: mdl-37909396

RÉSUMÉ

Diabetic foot ulcer (DFU) complications involve autophagy dysregulation. This study aimed to identify autophagy-related bioindicators in DFU. Differentially expressed genes (DEGs) between DFU and healthy samples were analysed from the Gene Expression Omnibus (GEO) datasets, GSE7014 and GSE29221. The roles of autophagy-related DEGs were investigated using protein-protein interaction (PPI) networks, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, Gene Ontology (GO) enrichment, and Gene Set Enrichment Analysis (GSEA). Immune cell infiltration's correlation with these DEGs was also assessed. From the Human Autophagy Database (HADB), 232 autophagy-related genes (ARGs) were identified, with an intersection of 17 key DEGs between GSE7014 and GSE29221. These genes are involved in pathways like autophagy-animal, NOD-like receptor signalling, and apoptosis. In the protein network, epidermal growth factor receptor (EGFR) and phosphatase and tensin homologue (PTEN) showed significant interactions with ARGs. Survival analysis indicated the prognostic importance of calpain 2 (CAPN2), integrin subunit beta 1 (ITGB1), and vesicle-associated membrane protein 3 (VAMP3). Lower immune scores were observed in the type 2 diabetes mellitus (DM2) group than in controls. Autophagy and ARGs significantly influence DFU pathophysiology.

19.
J Biomed Inform ; 146: 104488, 2023 Oct.
Article de Anglais | MEDLINE | ID: mdl-37678485

RÉSUMÉ

OBJECTIVE: To develop a hybrid neural network-based blood donation prediction method, via this predictive model, we can obtain the best estimate of whole blood in Beijing Tongzhou District Central Blood Station and help managers smoothly solve the allocation problem under fluctuating hospital demand and limited resources. METHOD: Inspired by the practical problems faced by blood stations providing transfusion services to several hospitals, a hybrid model based on a time-series prediction method and neural network, SARIMAX-TCN-LSTM is proposed for the prediction of daily whole blood donations. The experiment was performed at the central blood station in Tongzhou district, where we used whole blood donations from January 1, 2015, to November 14, 2021, as the subject, supplemented by meteorological and epidemic factors affecting blood donation, to predict daily blood donations for the next two weeks. RESULT: The hybrid model significantly outperformed the traditional time series forecasting method on multiple regression metrics, with twice as effective fitting as the baseline and a 33% reduction in Root Mean Squared Error (RMSE). Results indicate that the proposed model can improve the prediction accuracy of daily blood donations, and the co-validity of the structure was evidenced in an ablation experiment. CONCLUSION: Development and evaluation of a hybrid neural network-based model structure improve the prediction of daily blood donations. This intelligent forecasting method can help managers to overcome the challenges of sudden blood demand and contribute to the optimization of resource allocation tasks.

20.
Biomater Sci ; 11(21): 7158-7168, 2023 Oct 24.
Article de Anglais | MEDLINE | ID: mdl-37718624

RÉSUMÉ

MR-guided focused ultrasound surgery (MRgFUS) is driving a new direction in non-invasive thermal ablation therapy with spatial specificity and real-time temperature monitoring. Although widely used in clinical practice, it remains challenging to completely ablate the tumor margin due to fear of damaging the surrounding tissues, thus leading to low efficacy and a series of complications. Herein, we have developed novel pH-responsive drug-loading magnetosomes (STPSD nanoplatform) for increasing the T2-contrast and improved the ablation efficiency with a clinical MRgFUS system. Specifically, this STPSD nanoplatform is functionalized by pH-responsive peptides (STP-TPE), encapsulating superparamagnetic iron oxide (SPIO) and doxorubicin (DOX), which can cause drug release and SPIO deposition at the tumor site triggered by acidity and MRgFUS. Under MRgFUS treatment, the increased vascular permeability caused by hyperthermia can improve the uptake of SPIO and DOX by tumor cells, so as to enhance ultrasound energy absorption and further enhance the efficacy of chemotherapy to completely ablate tumor margins. Moreover, we demonstrated that a series of MR sequences including T2-weighted imaging (T2WI), contrast-enhanced T1WI imaging (T1WI C+), maximum intensity projection (MIP), volume rendering (VR) and ADC mapping can be further utilized to monitor the MRgFUS ablation effect in rat models. Overall, this smart nanoplatform has the capacity to be a powerful tool to promote the therapeutic MRgFUS effect and minimize the side effects to surrounding tissues.

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