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2.
World J Otorhinolaryngol Head Neck Surg ; 10(2): 113-120, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38855290

RESUMEN

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

3.
Int J Gen Med ; 17: 1739-1753, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38706747

RESUMEN

Purpose: To address the critical mortality rates among sepsis-associated acute kidney injury (SA-AKI) patients, early prognosis is vital. This study investigates the relationship between coagulation indices and the 28-day mortality rate in patients with SA-AKI. Patients and Methods: This study was a retrospective cohort analysis including patients with SA-AKI admitted to the First Hospital of Fujian Medical University as a training cohort (n = 119) and patients admitted to the Third People's Hospital of Fujian University of Traditional Chinese Medicine as a validation cohort (n = 51). We examined the relationship between coagulation indices and 28-day mortality in SA-AKI, the cumulative mortality at different activated partial thromboplastin time (APTT) levels, and the nonlinear relationship between APTT and 28-day mortality. Receiver operating characteristic curves were plotted, and the area under the curve was calculated to assess the predictive power of APTT. Finally, subgroup analyses were performed to assess the robustness of the association. Results: Overall, 119 participants with a mean±standard deviation age of 70.47±15.20 years were included in the training cohort: 54 died, 65 survived. According to univariate and multivariate COX regression analyses, APACHE II score, CRP level, Lac level, and APTT level were independent risk factors for 28-day adverse prognosis. After controlling for some variables, an elevated baseline APTT (≥ 37.7 s) was associated with an elevated risk of 28-day mortality (HR, 1.017; 95% CI, 1.001-1.032), and Kaplan-Meier analyses further confirmed the increased mortality in the group with a higher APTT. The same results were shown when the validation cohort was analyzed (HR, 1.024; 95% CI, 0.958-1.096). Subgroup analyses showed the stability of the association between APTT and poor prognosis in SA-AKI. Conclusion: In essence, APTT elevation is synonymous with increased 28-day mortality rates, indicating a poor prognosis in SA-AKI scenarios.

4.
Signal Transduct Target Ther ; 9(1): 108, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38705885

RESUMEN

Coinfusion of unrelated cord blood (UCB) units in haploidentical hematopoietic cell transplantation (haplo-HCT) (haplo-cord HCT) for hematopoietic malignancies showed promising results in previous reports, but the efficiency of haplo-cord HCT in acute myeloid leukemia (AML) still lacks sufficient evidence. This multicenter, randomized, phase 3 trial (ClinicalTrials.gov NCT03719534) aimed to assess the efficacy and safety of haplo-cord HCT in AML patients. A total of 268 eligible patients aged 18-60 years, diagnosed with measurable residual disease in AML (excluding acute promyelocytic leukemia), with available haploidentical donors and suitable for allotransplantation, were randomly allocated (1:1) to receive haplo-cord HCT (n = 134) or haplo-HCT (n = 134). The 3-year overall survival (OS) was the primary endpoint in this study. Overall median follow-up was 36.50 months (IQR 24.75-46.50). The 3-year OS of Haplo-cord HCT group was better than haplo-HCT group (80.5%, 95% confidence interval [CI]: 73.7-87.9 vs. 67.8% 95% CI 60.0-76.5, p = 0.013). Favorable progression-free survival (70.3%, 95% CI 62.6-78.8 vs. 57.6%, 95% CI 49.6-67.0, p = 0.012) and cumulative incidence of relapse (12.1%, 95% CI 12.0-12.2 vs. 30.3%, 95% CI 30.1-30.4, p = 0.024) were observed in haplo-cord HCT group. Grade 3-4 adverse events (AEs) within two years posttransplantation in the two groups were similar. Haplo-cord HCT patients exhibited a faster cumulative incidence of neutrophil recovery (p = 0.026) and increased T-cell reconstitution in the early period posttransplantation. Haplo-cord HCT can improve OS in AML patients without excessive AEs, which may exert additional benefits for recipients of haplo-HCT.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Adulto , Leucemia Mieloide Aguda/terapia , Masculino , Femenino , Persona de Mediana Edad , Adolescente , Trasplante Haploidéntico/efectos adversos , Adulto Joven
5.
Int Ophthalmol ; 44(1): 8, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38319543

RESUMEN

PURPOSE: The aim of this meta-analysis was to assess the efficacy of posterior scleral reinforcement (PSR) on the control of pediatric myopia. Electronic databases were systematically searched. METHODS: Standardized mean differences (SMDs) of outcomes were calculated. Eight studies with 357 patients with pediatric myopia were included. The SMD for the increase in mean axial length (AL) in the PSR and control group was - 1.19 (95% CI - 1.71, - 0.68). RESULTS: The SMD for decrease of best-corrected visual acuity (BCVA) LogMAR in the PSR and control group was 0.85 (95% CI 0.28, 1.43). The SMD for change in intraocular pressure (IOP) at the time of surgery and at the end of the follow-up period in the PSR group was - 0.01 (95% CI - 0.48, 0.47). CONCLUSION: This meta-analysis indicates that PSR surgery may be an effective therapeutic strategy to control the progression of myopia in childhood with acceptable adverse effects.


Asunto(s)
Presión Intraocular , Miopía , Humanos , Niño , Miopía/cirugía , Esclerótica/cirugía , Tonometría Ocular
7.
J Am Chem Soc ; 146(1): 187-200, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38118119

RESUMEN

The affinity and selectivity of small molecules for proteins drive drug discovery and development. We report a fluorescent probe cellular binding assay (FPCBA) for determination of these values for native (untagged) proteins overexpressed in living cells. This method uses fluorophores such as Pacific Blue (PB) linked to cell-permeable protein ligands to generate probes that rapidly and reversibly equilibrate with intracellular targets, as established by kinetic assays of cellular uptake and efflux. To analyze binding to untagged proteins, an internal ribosomal entry site (IRES) vector was employed that allows a single mRNA to encode both the protein target and a separate orthogonal fluorescent protein (mVenus). This enabled cellular uptake of the probe to be correlated with protein expression by flow cytometry, allowing measurement of cellular dissociation constants (Kd) of the probe. This approach was validated by studies of the binding of allosteric activators to eight different Protein Kinase C (PKC) isozymes. Full-length PKCs expressed in transiently transfected HEK293T cells were used to measure cellular Kd values of a probe comprising PB linked to the natural product phorbol via a carbamate. These values were further used to determine competitive binding constants (cellular Ki values) of the nonfluorescent phorbol ester PDBu and the anticancer agent bryostatin 1 for each isozyme. For some PKC-small molecule pairs, these cellular Ki values matched known biochemical Ki values, but for others, altered selectivity was observed in cells. This approach can facilitate quantification of interactions of small molecules with physiologically relevant native proteins.


Asunto(s)
Ésteres del Forbol , Proteína Quinasa C , Humanos , Células HEK293 , Proteína Quinasa C/química , Unión Competitiva
8.
J Immunol Methods ; 525: 113606, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38145790

RESUMEN

Tumor-associated glycoprotein 72 (TAG-72) is a mucin that is overexpressed heterogeneously on the surface of cancer cells, and is a potential target for immunotherapies for various cancer types. As a tumor marker, TAG-72 is measured with the cancer antigen (CA) 72-4 immunoassay. The murine monoclonal antibody (mAb) CC49 is a second-generation IgG that targets an antigen on TAG-72; however, CC49 has an unfavorable propensity to aggregate, which results in antibody impurity, instability, and low solubility and thus low potency and efficacy for therapeutic and diagnostic applications. Sequence analysis of CC49 revealed aggregation-prone motifs in the variable domain of the light chain. Using antibody engineering approaches, we developed three aggregation-resistant CC49 mIgG2a mutants (CC49M1, CC49M2, and CC49M3). The engineered CC49 mIgG2a mutants retained compatible binding performance with a significantly higher thermal stability. The CC49 mIgG2a mutants also demonstrated an almost 15-fold improvement in solubility, with 97% purity vs 70% purity of the parent molecule at 0.3 mg/mL. The enhanced stability and improved solubility of engineered CC49 could have significant advantages for diagnostic and therapeutic applications.


Asunto(s)
Antígenos de Neoplasias , Glicoproteínas , Ratones , Animales , Solubilidad , Antígenos de Neoplasias/genética , Anticuerpos Monoclonales , Inmunoglobulina G/genética
9.
Environ Technol ; : 1-11, 2023 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-37953724

RESUMEN

In order to further understand the effect of product inhibition on the metabolism of hydrogen production bacteria, and to seek an effective way to increase the hydrogen yield in fermentation, a simplified metabolic model of Ethanoligenens harbinense B49 was constructed to analyse the metabolic flux under acetate and ethanol inhibition separately and to analyse the flux changes of the nodes. Based on the changes in metabolic flux distribution, Glucose 6-phosphate (G6P), Pyruvate (PYR), and Acetyl-CoA (AcCoA) were identified as key nodes of hydrogen production in the metabolic network. Robustness analysis showed that G6P was flexible, while AcCoA and PYR were weakly rigid, indicating that acetate flux could be increased by adding inhibitors or using genetic manipulation. Furthermore, releasing inhibition of acetate could effectively increase hydrogen production. These findings suggested that the addition of acetate separation in ethanol-type fermentation process is expected to improve hydrogen production, which might be a promising way to full-scale produce biohydrogen in industrial applications. Further, for the first time, we report the effect of product inhibition on key nodes in the E. harbinense B49 hydrogen production metabolism network.

10.
Sci Rep ; 13(1): 20589, 2023 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-37996554

RESUMEN

Septic cardiomyopathy (SCM) is a common and severe complication of sepsis, characterized by left ventricular dilation and reduced ejection fraction leading to heart failure. The pathogenesis of SCM remains unclear. Understanding the SCM pathogenesis is essential in the search for effective therapeutic agents for SCM. This study was to investigate the pathophysiology of SCM and explore new therapeutic drugs by bioinformatics. An SCM rat model was established by injection of 10 mg/kg lipopolysaccharide (LPS) for 24 h, and the myocardial tissues were collected for RNA sequencing. The differentially expressed genes (DEGs) between LPS rats and control (Ctrl) with the thresholds of |log2fold change|≥ 1 and P < 0.05. A protein-protein interaction (PPI) network was constructed based on the DEGs. The hub genes were identified using five algorithms of Cytoscape in the PPI networks and validated in the GSE185754 dataset and by RT-qPCR. The hub genes were analyzed by Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG), as well as Gene set enrichment analyses (GSEA). In addition, the miRNAs of hub genes were predicted through miRWalk, and the candidate therapeutic drugs were identified using the Connectivity Map (CMAP) database. This study revealed the identified hub genes (Itgb1, Il1b, Rac2, Vegfa) and key miRNAs (rno-miR-541-5p, rno-miR-487b-3p, rno-miR-1224, rno-miR-378a-5p, rno-miR-6334, and rno-miR-466b-5p), which were potential biological targets and biomarkers of SCM. Anomalies in cytokine-cytokine receptor interactions, complement and coagulation cascades, chemokine signaling pathways, and MAPK signaling pathways also played vital roles in SCM pathogenesis. Two high-confidence candidate compounds (KU-0063794 and dasatinib) were identified from the CMAP database as new therapeutic drugs for SCM. In summary, these four identified hub genes and enrichment pathways may hold promise for diagnosing and treating SCM.


Asunto(s)
Cardiomiopatías , MicroARNs , Animales , Ratas , Lipopolisacáridos/efectos adversos , Transcriptoma , Cardiomiopatías/inducido químicamente , Cardiomiopatías/tratamiento farmacológico , Perfilación de la Expresión Génica , Biología Computacional , MicroARNs/genética
11.
Clin Proteomics ; 20(1): 53, 2023 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-38017436

RESUMEN

BACKGROUND: Diagnosis of liver disease at earlier stages can improve outcomes and reduce the risk of progression to malignancy. Liver biopsy is the gold standard for diagnosis of liver disease, but is invasive and sample acquisition errors are common. Serum biomarkers for liver function and fibrosis, combined with patient factors, may allow for noninvasive detection of liver disease. In this pilot study, we tested and validated the performance of an algorithm that combines GP73 and LG2m serum biomarkers with age and sex (GLAS) to differentiate between patients with liver disease and healthy individuals in two independent cohorts. METHODS: To develop the algorithm, prototype immunoassays were used to measure GP73 and LG2m in residual serum samples collected between 2003 and 2016 from patients with staged fibrosis and cirrhosis of viral or non-viral etiology (n = 260) and healthy subjects (n = 133). The performance of five predictive models using combinations of age, sex, GP73, and/or LG2m from the development cohort were tested. Residual samples from a separate cohort with liver disease (fibrosis, cirrhosis, or chronic liver disease; n = 395) and healthy subjects (n = 106) were used to validate the best performing model. RESULTS: GP73 and LG2m concentrations were higher in patients with liver disease than healthy controls and higher in those with cirrhosis than fibrosis in both the development and validation cohorts. The best performing model included both GP73 and LG2m plus age and sex (GLAS algorithm), which had an AUC of 0.92 (95% CI: 0.90-0.95), a sensitivity of 88.8%, and a specificity of 75.9%. In the validation cohort, the GLAS algorithm had an estimated an AUC of 0.93 (95% CI: 0.90-0.95), a sensitivity of 91.1%, and a specificity of 80.2%. In both cohorts, the GLAS algorithm had high predictive probability for distinguishing between patients with liver disease versus healthy controls. CONCLUSIONS: GP73 and LG2m serum biomarkers, when combined with age and sex (GLAS algorithm), showed high sensitivity and specificity for detection of liver disease in two independent cohorts. The GLAS algorithm will need to be validated and refined in larger cohorts and tested in longitudinal studies for differentiating between stable versus advancing liver disease over time.

12.
Ann Med ; 55(2): 2264318, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37791613

RESUMEN

BACKGROUND: Septic shock is the development of sepsis to refractory circulatory collapse and metabolic derangements, characterized by persistent hypotension and increased lactate levels. Anisodamine hydrobromide (Ani HBr) is a Chinese medicine used to improve blood flow in circulatory disorders. The purpose of this study was to determine the therapeutic efficacy of Ani HBr in the treatment of patients with septic shock. METHODS: This was a prospective, multicenter, randomized controlled trial focusing on patients with septic shock in 16 hospitals in China. Patients were randomly assigned in a 1:1 ratio to either the treatment group or the control group. The primary endpoint was 28-day mortality. The secondary outcomes included 7-day mortality, hospital mortality, hospital length of stay, vasopressor-free days within 7 days, etc. These indicators were measured and collected at 0, 6h, 24h, 48h, 72h and 7d after the diagnosis. RESULTS: Between September 2017 and March 2021, 404 subjects were enrolled. 203 subjects received Ani HBr and 201 subjects were assigned to the control group. The treated group showed lower 28-day mortality than the control group. Stratified analysis further showed significant differences in 28-day mortality between the two groups for patients with a high level of illness severity. We also observed significant differences in 7-day mortality, hospital mortality and some other clinical indicators between the two groups. CONCLUSION: Ani HBr might be an important adjuvant to conventional treatment to reduce 28-day mortality in patients with septic shock. A large-scale prospective randomized multicenter trial is warranted to confirm our results.


Asunto(s)
Sepsis , Choque Séptico , Humanos , Choque Séptico/tratamiento farmacológico , Enfermedad Crítica , Estudios Prospectivos
13.
Ear Nose Throat J ; : 1455613231205529, 2023 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-37840263

RESUMEN

Background: Arytenoid cartilage dislocation is considered as a rare laryngeal injury and closed reduction is commonly used as the first choice for the arytenoid dislocation. However, the tools of closed reduction vary, and there is no dedicated tool for closed reduction, and the treatment outcome varies from person to person. This study compared the treatment outcome of the modified laryngeal forceps and traditional laryngeal forceps. Material and Methods: This study conformed to the strengthening the reporting of observational studies in epidemiology guidelines regarding retrospective studies. From May 2021 to February 2023, the records of 28 patients with arytenoid cartilage dislocation caused by endotracheal intubation were reviewed. They were divided into the traditional group (n = 14) and the modified group (n = 14) by gender. Indirect or direct laryngoscopy, video stroboscopy, high-resolution computed tomography, and cricoarytenoid joint 3-dimensional reconstruction were used to evaluate arytenoid position and motion. Clinical characteristics, voice function, procedural skill, and treatment outcome for each case were recorded. Results: Each patient was diagnosed with arytenoid dislocation caused by endotracheal intubation. There was no significant difference in the treatment outcome between the traditional group and the modified group (P > .05). However, the median time interval between closed reduction and the return of normal voice in the traditional group was 31.08 ± 10.56 days, which was significantly longer than the median time of 17.92 ± 3.83 days in the modified group (P < .05). Conclusion: Closed reduction with the modified laryngeal forceps under local anesthesia is an effective and safe procedure. Compared with traditional laryngeal forceps, the modified laryngeal forceps can shorten the treatment duration.

14.
Artif Intell Med ; 143: 102611, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37673579

RESUMEN

Medical Visual Question Answering (VQA) is a combination of medical artificial intelligence and popular VQA challenges. Given a medical image and a clinically relevant question in natural language, the medical VQA system is expected to predict a plausible and convincing answer. Although the general-domain VQA has been extensively studied, the medical VQA still needs specific investigation and exploration due to its task features. In the first part of this survey, we collect and discuss the publicly available medical VQA datasets up-to-date about the data source, data quantity, and task feature. In the second part, we review the approaches used in medical VQA tasks. We summarize and discuss their techniques, innovations, and potential improvements. In the last part, we analyze some medical-specific challenges for the field and discuss future research directions. Our goal is to provide comprehensive and helpful information for researchers interested in the medical visual question answering field and encourage them to conduct further research in this field.


Asunto(s)
Inteligencia Artificial
16.
Ann Noninvasive Electrocardiol ; 28(5): e13071, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37469208

RESUMEN

OBJECTIVE: To investigate the safety and effectiveness of implanting temporary pacemakers using ultrasound-guidance at the bedside for rescuing patients in case of cardiac emergencies. METHODS: We enrolled 194 patients with cardiac emergencies requiring temporary pacemakers in this study, and randomly assigned them to either a bedside ultrasound-guided installation group or an electrocardiogram-guided installation group. There were 105 cases in the bedside ultrasound-guided installation group, aged approximately 66.3 ± 10.2 years, and 89 cases in the electrocardiogram-guided installation group, aged approximately 65.8 ± 9.5 years old, and disease composition was similar between the two groups. We then compared the duration of the procedure, success rates, and occurrence of adverse events between the two groups. RESULTS: The two groups showed similar clinical characteristics. The success rates of venipuncture and temporary pacemaker electrode placement were both 100% in the bedside ultrasound-guided installation group, compared to 87.8% and 96.7% respectively, in the electrocardiogram-guided installation group, with a statistically significant difference between the two groups. The duration of puncture was significantly shorter in the bedside ultrasound-guided installation group than in the electrocardiogram-guided installation group, with statistically significant differences. Moreover, no adverse events such as hematoma, pneumothorax and electrode dislodgement occurred in the bedside ultrasound-guided installation group, while 13 cases in the electrocardiogram-guided installation group experienced adverse events, and the difference was statistically significant. CONCLUSIONS: The bedside installation of temporary pacemakers using ultrasound guidance is a simple, safe, effective, and cost-efficient procedure that boasts a high success rate, does not involve radiation, and enables accurate placement of the electrode catheter.


Asunto(s)
Urgencias Médicas , Marcapaso Artificial , Anciano , Humanos , Persona de Mediana Edad , Electrocardiografía , Corazón , Ultrasonografía Intervencional/métodos
17.
Acta Otolaryngol ; 143(4): 322-327, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37093046

RESUMEN

BACKGROUND: It is uncertain which factors substantially influence outcomes after uvulopalatopharyngoplasty (UPPP) in patients with supine predominant obstructive sleep apnea (POSA). OBJECTIVE: To explore the predictors of UPPP outcomes in POSA patients. METHODS: A total of 108 patient(52 positional patients (POSA) and 56 nonpositional patients(NPP)), who underwent the revised uvulopalatopharyngoplasty (H-UPPP), were retrospectively studied. The pre-operative information of these patients, including polysomnography (PSG), and upper airway CT, were collected for analysis. RESULTS: No difference was found in surgical success rates between POSA and NPP undergoing H-UPPP. In POSA patients, there were statistically significant differences between responders and nonresponders in body mass index (BMI), preoperative supine AHI, time of SaO2 < 90% (TS90) (all p < .05), minimal anteroposterior airway (mAP) (p = .016), minimal lateral airway (mLAT) (p = .002), minimal cross-sectional airway area (mCSA) (p < .001) at the velopharynx. mLAT (p = .014) and mCSA (p = .002) at the glossopharynx. The independent associated factors for surgical success were lower BMI (p < .001), narrowerm LAT (p = .002) and mAP (p < .001) at velopharynx, and wider mCSA (p < .001) at glossopharynx in POSA. CONCLUSION: POSA patients with lower BMI, narrower mLAT and mAP at velopharynx, wider mCSA at glossopharynx were more likely to achieve a positive outcome with H-UPPP.


Asunto(s)
Apnea Obstructiva del Sueño , Humanos , Estudios Retrospectivos , Estudios Transversales , Posición Supina , Apnea Obstructiva del Sueño/cirugía , Úvula/cirugía
18.
J Thromb Haemost ; 21(8): 2163-2174, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37061131

RESUMEN

BACKGROUND: Mitochondrial calcium uniporter b (MCUb) is a negative regulator of the mitochondrial calcium uniporter (MCU) and is known to limit mitochondrial calcium ion (Ca2+) uptake. The role of MCUb in platelet function remains unclear. OBJECTIVES: Utilizing MCUb-/- mice, we examined the role of MCUb in regulating platelet function and thrombosis. METHODS: Platelet activation was evaluated in agonist-induced standardized in vitro assays. Susceptibility to arterial thrombosis was evaluated in FeCl3 injury-induced carotid artery and laser injury-induced mesenteric artery thrombosis models. The glycolytic proton efflux rate and oxygen consumption rate were measured to evaluate aerobic glycolysis. RESULTS: Upon stimulation, MCUb-/- platelets exhibited reduced cytoplasmic Ca2+ responses concomitant with increased mitochondrial Ca2+ uptake. MCUb-/- platelets displayed reduced agonist-induced platelet aggregation and spreading on fibrinogen and decreased α and dense-granule secretion and clot retraction. MCUb-/- mice were less susceptible to arterial thrombosis in FeCl3 injury-induced carotid and laser injury-induced mesenteric thrombosis models with unaltered tail bleeding time. In adoptive transfer experiments, thrombocytopenic hIL-4Rα/GPIbα-transgenic mice transfused with MCUb-/- platelets were less susceptible to FeCl3 injury-induced carotid thrombosis compared with hIL-4Rα/GPIbα-Tg mice transfused with wild type platelets, suggesting a platelet-specific role of MCUb in thrombosis. MCUb-/- stimulated platelets exhibited reduced glucose uptake, decreased glycolytic rate, and lowered pyruvate dehydrogenase phosphorylation, suggesting that mitochondrial Ca2+ mediates bioenergetic changes in platelets. CONCLUSION: Our findings suggest that mitochondrial Ca2+ signaling and glucose oxidation are functionally linked in activated platelets and reveal a novel role of MCUb in platelet activation and arterial thrombosis.


Asunto(s)
Hemostasis , Trombosis , Ratones , Animales , Agregación Plaquetaria , Plaquetas , Activación Plaquetaria , Ratones Transgénicos , Ratones Noqueados , Calcio
19.
Ophthalmic Res ; 66(1): 664-671, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36858031

RESUMEN

INTRODUCTION: This study analyzed the effectiveness of 650-nm red-light feeding instruments in the control of myopia. METHODS: In this study, 164 school-aged participants diagnosed with myopia in the city of Shenzhen were enrolled in a red-light feeding instrument study. Of these, 41 were enrolled in the mild-to-moderate myopia group that received red-light feeding (RLMM group), 65 were enrolled in the mild-to-moderate myopia group that received single-vision spectacle treatment (SVSMM group), and 58 were included in the severe myopia group that received red-light feeding (RLS group). RESULTS: After the baseline values of the three groups were matched, the right eye data were used for statistical analysis. The average return visit time of each group was 60.42 days, and changes in the observation indexes before treatment and after follow-up treatment were compared. As the primary outcome, the axial length changes in the right eye of the SVSMM group (0.08 ± 0.40 mm), the RLMM group (-0.03 ± 0.11 mm), and the RLS group (-0.07 ± 0.11 mm) were compared and showed a statistical result of p < 0.001. CONCLUSION: The study results verified that red light had a noticeable effect on the control of myopia and that low-level red-light therapy played a vital role in the treatment of severe myopia.


Asunto(s)
Miopía , Refracción Ocular , Humanos , Niño , Miopía/terapia , Ojo , Luz Roja , Anteojos
20.
Clin Chem Lab Med ; 61(8): 1511-1517, 2023 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-36799248

RESUMEN

OBJECTIVES: To evaluate pre-analytical challenges related to high-volume central laboratory SARS-CoV-2 antigen testing with a prototype qualitative SARS-CoV-2 antigen immunoassay run on the automated Abbott ARCHITECT instrument. METHODS: Contrived positive and negative specimens and de-identified nasal and nasopharyngeal specimens in transport media were used to evaluate specimen and reagent on-board stability, assay analytical performance and interference, and clinical performance. RESULTS: TCID50/mL values were similar for specimens in various transport media. Inactivated positive clinical specimens and viral lysate (USA-WA1/2020) were positive on the prototype immunoassay. Within-laboratory imprecision was ≤0.10 SD (<1.00 S/C) with a ≤10% CV (≥1.00 S/C). Assay reagents were stable on board the instrument for 14 days. No high-dose hook effect was observed with a SARS-CoV-2 stock of Ct 13.0 (RLU>1.0 × 106). No interference was observed from mucin, whole blood, 12 drugs, and more than 20 cross-reactants. While specimen stability was limited at room temperature for specimens with or without viral inactivation, a single freeze/thaw cycle or long-term storage (>30 days) at -20 °C did not adversely impact specimen stability or assay performance. Specificity of the prototype SARS-CoV-2 antigen immunoassay was ≥98.5% and sensitivity was ≥89.5% across two ARCHITECT instruments. Assay sensitivity was inversely correlated with Ct and was similar to that reported for the Roche Elecsys® SARS-CoV-2 Ag immunoassay. CONCLUSIONS: The prototype SARS-CoV-2 antigen ARCHITECT immunoassay is sensitive and specific for detection of SARS-CoV-2 in nasal and nasopharyngeal specimens. Endogenous proteases in mucus may degrade the target antigen, which limits specimen storage and transport times and complicates assay workflow.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , Sensibilidad y Especificidad , Prueba de COVID-19 , Inmunoensayo
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