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BACKGROUND: Preschoolers become anxious when they are about to undergo anesthesia and surgery, warranting the development of more appropriate and effective interventions. AIM: To explore the effect of static cartoons combined with dynamic virtual environments on preoperative anxiety and anesthesia induction compliance in preschool-aged children undergoing surgery. METHODS: One hundred and sixteen preschool-aged children were selected and assigned to the drug (n = 37), intervention (n = 40), and control (n = 39) groups. All the children received routine preoperative checkups and nursing before being transferred to the preoperative preparation room on the day of the operation. The drug group received 0.5 mg/kg midazolam and the intervention group treatment consisting of static cartoons combined with dynamic virtual environments. The control group received no intervention. The modified Yale Preoperative Anxiety Scale was used to evaluate the children's anxiety level on the day before surgery (T0), before leaving the preoperative preparation room (T1), when entering the operating room (T2), and at anesthesia induction (T3). Compliance during anesthesia induction (T3) was evaluated using the Induction Compliance Checklist (ICC). Changes in mean arterial pressure (MAP), heart rate (HR), and respiratory rate (RR) were also recorded at each time point. RESULTS: The anxiety scores of the three groups increased variously at T1 and T2. At T3, both the drug and intervention groups had similar anxiety scores, both of which were lower than those in the control group. At T1 and T2, MAP, HR, and RR of the three groups increased. The drug and control groups had significantly higher MAP and RR than the intervention group at T2. At T3, the MAP, HR, and RR of the drug group decreased and were significantly lower than those in the control group but were comparable to those in the intervention group. Both the drug and intervention groups had similar ICC scores and duration of anesthesia induction (T3), both of which were higher than those of the control group. CONCLUSION: Combining static cartoons with dynamic virtual environments as effective as medication, specifically midazolam, in reducing preoperative anxiety and fear in preschool-aged children. This approach also improve their compliance during anesthesia induction and helped maintain their stable vital signs.
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Endovascular treatment (EVT) using stents has become the primary option for severe cerebrovascular stenosis. However, considerable challenges remain to be addressed, such as in-stent restenosis (ISR) and late thrombosis. Many modified stents have been developed to inhibit the hyperproliferation of vascular smooth muscle cells (SMCs) and protect vascular endothelial cells (VECs), thereby reducing such complications. Some modified stents, such as those infused with rapamycin, have improved in preventing acute thrombosis. However, ISR and late thrombosis, which are long-term complications, remain unavoidable. Panax notoginseng saponin (PNS), a traditional Chinese medicine consisting of various compounds, is beneficial in promoting the proliferation and migration of VECs and inhibiting the proliferation of SMCs. Herein, a 3D-printed polycaprolactone (PCL) stent loaded with PNS (PNS-PCL stent) was developed based on a previous study. In vitro studies confirmed that PNS promotes the migration and proliferation of VECs, which were damaged, by increasing the expression levels of microRNA-126, p-AKT, and endothelial nitric oxide synthase. In vivo, the PNS-PCL stents maintained the patency of the carotid artery in rabbits for up to three months, outperforming the PCL stents. The PNS-PCL stents may present a new solution for the EVT of cerebrovascular atherosclerotic stenosis in the future.
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Introduction: Epilepsy is a common neurological condition that affects a large number of individuals worldwide. One of the primary challenges in epilepsy is the accurate and timely detection of seizure. Recently, the graph regularized broad learning system (GBLS) has achieved superior performance improvement with its flat structure and less time-consuming training process compared to deep neural networks. Nevertheless, the number of feature and enhancement nodes in GBLS is predetermined. These node settings are also randomly selected and remain unchanged throughout the training process. The characteristic of randomness is thus more easier to make non-optimal nodes generate, which cannot contribute significantly to solving the optimization problem. Methods: To obtain more optimal nodes for optimization and achieve superior automatic detection performance, we propose a novel broad neural network named self-adaptive evolutionary graph regularized broad learning system (SaE-GBLS). Self-adaptive evolutionary algorithm, which can construct mutation strategies in the strategy pool based on the experience of producing solutions for selecting network parameters, is incorporated into SaE-GBLS model for optimizing the node parameters. The epilepsy seizure is automatic detected by our proposed SaE-GBLS model based on three publicly available EEG datasets and one private clinical EEG dataset. Results and discussion: The experimental results indicate that our suggested strategy has the potential to perform as well as current machine learning approaches.
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Drought significantly impacts cotton square (flower buds with bracts) shedding, directly affecting yield. To address the internal physiological mechanisms of drought affecting cotton square shedding, a polyethylene glycol-simulated drought study was conducted with Dexiamian 1 and Yuzaomian 9110 to investigate cell wall degradation changes in the base of pedicel where the detachment of cotton square takes place, and its relationship with cotton square shedding. Results revealed significant decreases in cellulose, hemicellulose, and pectin contents in the base of square pedicel, leading to cell wall degradation and consequent square shedding. Furthermore, drought stress exacerbated the hydrolysis of cellulose and pectin in the base of pedicel, although not hemicellulose, resulting in more noticeable alterations in the morphology and structure of the base of pedicel, such as more significant degradation in the epidermis, cortex, and phloem. Regarding the cellulose hydrolysis, drought mainly increased the expression of genes ß-glucosidase (GhBG1) and endoglucanase (GhEG1), and the activity of ß-glucosidase and endoglucanase in the base of pedicel, promoting the conversion of cellulose to cellobiose, and eventually glucose. Regarding the pectin hydrolysis, drought significantly enhanced the expression of the gene pectin methylase (GhPE1), thereby accelerating pectin hydrolysis to generate polygalacturonic acid. Additionally, drought increased the expression of genes pectin lyase (GhPL1) and polygalacturonase (GhPG1), as well as the activity of pectin lyase, which further accelerated the hydrolysis of polygalacturonic acid into galacturonic acid. These findings suggest that drought mainly promotes cellulose and pectin hydrolysis in the base of pedicel, hastening cell wall degradation and final cotton square shedding.
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Pared Celular , Sequías , Gossypium , Pectinas , Pared Celular/metabolismo , Gossypium/metabolismo , Gossypium/genética , Pectinas/metabolismo , Celulosa/metabolismo , Flores/metabolismo , Hidrólisis , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Polisacáridos/metabolismoRESUMEN
PURPOSE: To delineate the alterations in adipose and muscle tissue composition and functionality among healthy young men across varying exercise intensities, which help to elucidate the impact of exercise intensity on weight management and inform fitness planning. METHOD: 3D Dixon MRI scans were performed on the neck and supraclavicular area in 10 high-intensity exercises (HIE) athletes, 20 moderate intensity exercises (MIE) athletes and 19 low-intensity exercises non-athlete male controls (NCM). Twelve imaging parameters, including the total volume of muscle, white adipose tissue (WAT), brown adipose tissue (BAT), and the mean fat-water fraction (FWF) within these tissues. Additionally, ratios of BAT or WAT to total fat (BATr or WATr) and the proportions of muscle, BAT, or WAT to total tissue volume (Musp, BATp, and WATp) were calculated. Parameters were compared across groups and correlated with Body Mass Index (BMI), waistline, and hipline. RESULTS: The HIE group exhibited the highest total muscle (totalMUS) and brown adipose tissue (totalBAT) volumes among the three groups. Conversely, the NCM group had significantly higher fwfFAT and fwfBAT values. The MUSp was higher in the HIE and MIE groups compared to NCM, while the BATp and WATp were lower. Furthermore, the BATr in HIE and MIE groups were higher than NCM group while the WATr were lower. Significant linear relationships were observed between totalBAT, totalWAT, MUSp, BATr, fwfFAT, and BMI, waistline (P < 0.05) across all groups. CONCLUSIONS: MIE is sufficient for the purpose of weight control, While HIE helps to further increase the muscle mass. All three physical indexes were significantly associated with the image parameters, with waistline emerging as the most effective indicator for detecting metabolic changes across all groups.
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Tejido Adiposo , Ejercicio Físico , Imagen por Resonancia Magnética , Músculo Esquelético , Humanos , Masculino , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/metabolismo , Imagen por Resonancia Magnética/métodos , Ejercicio Físico/fisiología , Adulto Joven , Tejido Adiposo/diagnóstico por imagen , Tejido Adiposo/metabolismo , Adulto , Imagenología Tridimensional/métodosRESUMEN
Chlamydia psittaci pneumonia (CPP) is a lung disease caused by the infection with the Chla-mydia psittaci bacterium, which can lead to severe acute respiratory distress syndrome and systemic symptoms. This study explored the specific mechanisms underlying the impact of reactive oxygen species (ROS) on the Th17/Treg balance in CPP. The levels of ROS and the differentiation ratio of Th17/Treg in the peripheral blood of healthy individuals and CPP patients were measured using ELISA and flow cytometry, respectively. The association between the ROS levels and Th17/Treg was assessed using Pearson correlation analysis. The ROS levels and the Th17/Treg ratio were measured in CD4+ T cells following H2O2 treatment and NLRP3 inhibition. The effects of H2O2 treatment and NLRP3 inhibition on the NLRP3/IL-1ß/caspase-1 pathway were observed using immunoblotting. Compared to the healthy group, the CPP group exhibited increased levels of ROS in the peripheral blood, an elevated ratio of Th17 differentiation, and a decreased ratio of Treg differentiation. ROS levels were positively correlated with the Th17 cell proportion but negatively correlated with the Treg cell proportion. The ROS levels and NLRP3/IL-1ß/caspase-1 expression were up-regulated in CD4+ T cells after H2O2 treatment. Furthermore, there was an increase in Th17 differentiation and a decrease in Treg differentiation. Conversely, the NLRP3/IL-1ß/caspase-1 pathway inhibition reversed the effects of H2O2 treatment, with no significant change in the ROS levels. ROS regulates the Th17/Treg balance in CPP, possibly through the NLRP3/IL-1ß/caspase-1 pathway. This study provides a new perspective on the development of immunotherapy for CPP.
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Caspasa 1 , Diferenciación Celular , Chlamydophila psittaci , Interleucina-1beta , Proteína con Dominio Pirina 3 de la Familia NLR , Especies Reactivas de Oxígeno , Linfocitos T Reguladores , Células Th17 , Humanos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Células Th17/inmunología , Células Th17/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Linfocitos T Reguladores/inmunología , Caspasa 1/metabolismo , Diferenciación Celular/efectos de los fármacos , Interleucina-1beta/metabolismo , Transducción de Señal , Masculino , Femenino , Persona de Mediana Edad , Adulto , Peróxido de Hidrógeno/metabolismo , PsitacosisRESUMEN
Partial root-zone drying irrigation (PRD) can improve water-use efficiency (WUE) without reductions in photosynthesis; however, the mechanism by which this is attained is unclear. To amend that, PRD conditions were simulated by polyethylene glycol 6000 in a root-splitting system and the effects of PRD on cotton growth were studied. Results showed that PRD decreased stomatal conductance (gs) but increased mesophyll conductance (gm). Due to the contrasting effects on gs and gm, net photosynthetic rate (AN) remained unaffected, while the enhanced gm/gs ratio facilitated a larger intrinsic WUE. Further analyses indicated that PRD-induced reduction of gs was related to decreased stomatal size and stomatal pore area in adaxial and abaxial surface which was ascribed to lower pore length and width. PRD-induced variation of gm was ascribed to the reduced liquid-phase resistance, due to increases in chloroplast area facing to intercellular airspaces and the ratio of chloroplast surface area to total mesophyll cell area exposed to intercellular airspaces, as well as to decreases in the distance between cell wall and chloroplast, and between adjacent chloroplasts. The above results demonstrate that PRD, through alterations to stomatal and mesophyll structures, decoupled gs and gm responses, which ultimately increased intrinsic WUE and maintained AN.
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Riego Agrícola , Gossypium , Células del Mesófilo , Fotosíntesis , Hojas de la Planta , Raíces de Plantas , Estomas de Plantas , Agua , Gossypium/fisiología , Gossypium/metabolismo , Estomas de Plantas/fisiología , Células del Mesófilo/metabolismo , Células del Mesófilo/fisiología , Agua/metabolismo , Raíces de Plantas/fisiología , Raíces de Plantas/metabolismo , Hojas de la Planta/fisiología , Hojas de la Planta/metabolismo , Transpiración de Plantas/fisiología , Cloroplastos/metabolismo , DesecaciónRESUMEN
OBJECTIVES: Our study aims to investigate the impact of B-mode ultrasound (B-US) imaging, color Doppler flow imaging (CDFI), strain elastography (SE), and patient age on the prediction of molecular subtypes in breast lesions. METHODS: Totally 2272 multimodal ultrasound imaging was collected from 198 patients. The ResNet-18 network was employed to predict four molecular subtypes from B-US imaging, CDFI, and SE of patients with different ages. All the images were split into training and testing datasets by the ratio of 80%:20%. The predictive performance on testing dataset was evaluated through 5 metrics including mean accuracy, precision, recall, F1-scores, and confusion matrix. RESULTS: Based on B-US imaging, the test mean accuracy is 74.50%, the precision is 74.84%, the recall is 72.48%, and the F1-scores is 0.73. By combining B-US imaging with CDFI, the results were increased to 85.41%, 85.03%, 85.05%, and 0.84, respectively. With the integration of B-US imaging and SE, the results were changed to 75.64%, 74.69%, 73.86%, and 0.74, respectively. Using images from patients under 40 years old, the results were 90.48%, 90.88%, 88.47%, and 0.89. When images from patients who are above 40 years old, they were changed to 81.96%, 83.12%, 80.5%, and 0.81, respectively. CONCLUSION: Multimodal ultrasound imaging can be used to accurately predict the molecular subtypes of breast lesions. In addition to B-US imaging, CDFI rather than SE contribute further to improve predictive performance. The predictive performance is notably better for patients under 40 years old compared with those who are 40 years old and above.
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Neoplasias de la Mama , Mama , Aprendizaje Profundo , Diagnóstico por Imagen de Elasticidad , Ultrasonografía Mamaria , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Adulto , Persona de Mediana Edad , Ultrasonografía Mamaria/métodos , Diagnóstico por Imagen de Elasticidad/métodos , Factores de Edad , Anciano , Mama/diagnóstico por imagen , Ultrasonografía Doppler en Color/métodos , Adulto Joven , Valor Predictivo de las Pruebas , Algoritmos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Anciano de 80 o más AñosRESUMEN
Radiodynamic therapy (RDT) has emerged as a promising modality for cancer treatment, offering notable advantages such as deep tissue penetration and radiocatalytic generation of oxygen free radicals. However, the oxygen-dependent nature of RDT imposes limitations on its efficacy in hypoxic conditions, particularly in modulating and eliminating radioresistant immune suppression cells. A novel approach involving the creation of a "super" tetrahedron polyoxometalate (POM) cluster, Fe12-POM, has been developed for radiation boosted chemodynamic catalysis to enable oxygen-independent RDT in hypoxic conditions. This nanoscale cluster comprises four P2W15 units functioning as energy antennas, while the Fe3 core serves as an electron receptor and catalytic center. Under X-ray radiation, a metal-to-metal charge transfer phenomenon occurs between P2W15 and the Fe3 core, resulting in the valence transition of Fe3+ to Fe2+ and a remarkable 139-fold increase in hydroxyl radical generation compared to Fe12-POM alone. The rapid generation of hydroxyl radicals, in combination with PD-1 therapy, induces a reprogramming of the immune environment within tumors. This reprogramming is characterized by upregulation of CD80/86, downregulation of CD163 and FAP, as well as the release of interferon-γ and tumor necrosis factor-α. Consequently, the occurrence of abscopal effects is facilitated, leading to significant regression of both local and distant tumors in mice. The development of oxygen-independent RDT represents a promising approach to address cancer recurrence and improve treatment outcomes.
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Microambiente Tumoral , Animales , Ratones , Humanos , Microambiente Tumoral/efectos de los fármacos , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Oxígeno/química , Compuestos de Tungsteno/química , Compuestos de Tungsteno/farmacología , Línea Celular TumoralRESUMEN
The potential mechanisms by which drought restricts cotton fiber cell wall synthesis and fiber strength are still not fully understood. Herein, drought experiments were conducted using two cultivars of upland cotton (Gossypium hirsutum), Dexiamian 1 (drought-tolerant) and Yuzaomian 9110 (drought-sensitive). Results showed that drought notably reduced sucrose efflux from cottonseed coats to fibers by down-regulating the expression of GhSWEET10 and GhSWEET15 in outer cottonseed coats, leading to enhanced sucrose accumulation in cottonseed coats but decreased sucrose accumulation in fibers. Within cotton fibers, drought restricted the hydrolysis of sucrose to uridine-5'-diphosphoglucose by suppressing sucrose synthase activity, and drought favored the conversion of uridine-5'-diphosphoglucose to ß-1,3-glucan rather than cellulose by up-regulating GhCALS5. Hence, cellulose content was reduced, which was the main reason for the decreased fiber strength under drought. Moreover, drought promoted lignin synthesis by up-regulating the expression of Gh4CL4, GhPAL9, GhCCR5, GhCAD11, and GhCOMT6, which partly offset the negative influence of reduced cellulose content on fiber strength. Compared with Yuzaomian 9110, the drought-tolerance of Dexiamian 1 was evidenced by the following under drought conditions: (i) greater sucrose flow from seedcoat to fiber, (ii) less ß-1,3-glucan accumulation, and (iii) more lignin biosynthesis. Overall, this study provides new insights into the mechanism of reduced cotton fiber strength induced by drought.
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Fibra de Algodón , Sequías , Gossypium , Sacarosa , Sacarosa/metabolismo , Gossypium/metabolismo , Gossypium/genética , Gossypium/fisiología , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Celulosa/metabolismo , Glucosiltransferasas/metabolismo , Glucosiltransferasas/genéticaRESUMEN
Yield of cotton (Gossypium hirsutum) does not always fall with high temperature (HT) even though this induces significant reductions in fruit retention. To investigate the underlying mechanisms, a greenhouse experiment was conducted with two temperature regimes [control treatment, 28 °C; high temperature (HT), 34 °C] for 7 d. Results showed HT did not significantly influence cotton yield, but reduced boll number and increased boll weight. The 13C distribution ratio of the leaf subtending the cotton boll (LSCB) decreased while that of the cotton boll increased under HT. Transcriptomic and proteomic analyses of the LSCB revealed up-regulated genes involved in cytokinin and jasmonic acid synthesis, as well as SWEET15 (GH_D01G0218), which positively regulated photosynthesis and transport photosynthate, ultimately leading to increased boll weight. After 7 d recovery from HT, the 13C distribution ratio of the LSCB increased while that of the cotton boll decreased. However, boll weight still increased, which was related to increased amylase and sucrose phosphate synthase activities and up-regulated sucrose transport genes in the main-stem leaf and capsule wall. Thus, both accelerated sucrose synthesis and transport in the LSCB under HT and increased sucrose supply ability of the main-stem leaf and capsule wall after recovery from HT contributed to an increased boll weight, which finally maintained cotton yield.
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Gossypium , Fotosíntesis , Gossypium/metabolismo , Gossypium/genética , Gossypium/crecimiento & desarrollo , Gossypium/fisiología , Calor , Metabolismo de los Hidratos de Carbono , Hojas de la Planta/metabolismo , Hojas de la Planta/fisiología , Regulación de la Expresión Génica de las PlantasRESUMEN
Elevated levels of reactive oxygen species (ROS) have demonstrated efficacy in eliminating tumor cells by modifying the tumor microenvironment and inducing the polarization of tumor-associated macrophages (TAMs). Nevertheless, the transient nature and limited diffusion distance inherent in ROS present significant challenges in cancer treatment. In response to these limitations, we have developed a nanoparticle (MnClPc-HSA@GOx) that not only inhibits tumor energy metabolism but also facilitates the transition of TAMs from the M2 type (anti-inflammatory type) to the M1 type (proinflammatory type). MnClPc-HSA@GOx comprises a manganese phthalocyanine complex (MnClPc) enveloped in human serum albumin (HSA), with glucose oxidase (GOx) loaded onto MnClPc@HSA nanoparticles. GOx was employed to catalyze the decomposition of glucose to produce H2O2 and gluconic acid. Additionally, in the presence of MnClPc, it catalyzes the conversion of H2O2 into â¢O2- and 1O2. Results indicate that the nanoparticle effectively impedes the glucose supply to tumor cells and suppresses their energy metabolism. Simultaneously, the ROS-mediated polarization of TAMs induces a shift from M2 to M1 macrophages, resulting in a potent inhibitory effect on tumors. This dual-action strategy holds promising clinical inhibition applications in the treatment of cancer.
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Isoindoles , Nanopartículas , Neoplasias , Humanos , Manganeso/farmacología , Glucosa Oxidasa/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Peróxido de Hidrógeno/metabolismo , Neoplasias/metabolismo , Macrófagos , Oxígeno/metabolismo , Metabolismo Energético , Glucosa , Microambiente TumoralRESUMEN
Purpose: The objective of this study was to develop a fully automatic mass segmentation method called AMS-U-Net for digital breast tomosynthesis (DBT), a popular breast cancer screening imaging modality. The aim was to address the challenges posed by the increasing number of slices in DBT, which leads to higher mass contouring workload and decreased treatment efficiency. Approach: The study used 50 slices from different DBT volumes for evaluation. The AMS-U-Net approach consisted of four stages: image pre-processing, AMS-U-Net training, image segmentation, and post-processing. The model performance was evaluated by calculating the true positive ratio (TPR), false positive ratio (FPR), F-score, intersection over union (IoU), and 95% Hausdorff distance (pixels) as they are appropriate for datasets with class imbalance. Results: The model achieved 0.911, 0.003, 0.911, 0.900, 5.82 for TPR, FPR, F-score, IoU, and 95% Hausdorff distance, respectively. Conclusions: The AMS-U-Net model demonstrated impressive visual and quantitative results, achieving high accuracy in mass segmentation without the need for human interaction. This capability has the potential to significantly increase clinical efficiency and workflow in DBT for breast cancer screening.
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This study aimed to explore the effectiveness and safety of azvudine, nirmatrelvir/ritonavir, and molnupiravir in adult patients with mild-to-moderate COVID-19. This retrospective cohort study included patients with mild-to-moderate COVID-19 (asymptomatic, mild, and common types) at the First Hospital of Changsha (Hunan Province, China) between March and November 2022. Eligible patients were classified into the azvudine, nirmatrelvir/ritonavir, or molnupiravir groups according to the antiviral agents they received. The outcomes were the times to nucleic acid negative conversion (NANC). This study included 157 patients treated with azvudine (n = 66), molnupiravir (n = 66), or nirmatrelvir/ritonavir (n = 25). There were no statistically significant differences in the time from diagnosis to NANC among the azvudine, molnupiravir, and nirmatrelvir/ritonavir groups [median, 9 (95% CI 9-11) vs. 11 (95% CI 10-12) vs. 9 (95% CI 8-12) days, P = 0.15], time from administration to NANC [median, 9 (95% CI 8-10) vs. 10 (95% CI 9.48-11) vs. 8.708 (95% CI 7.51-11) days, P = 0.50], or hospital stay [median, 11 (95% CI 11-13) vs. 13 (95% CI 12-14) vs. 12 (95% CI 10-14) days, P = 0.14], even after adjustment for sex, age, COVID-19 type, comorbidities, Ct level, time from diagnosis to antiviral treatment, and number of symptoms. The cumulative NANC rates in the azvudine, molnupiravir, and nirmatrelvir/ritonavir groups were 15.2%/12.3%/16.0% at day 5 (P = 0.858), 34.8%/21.5%/32.0% at day 7 (P = 0.226), 66.7%/52.3%/60.0% at 10 days (P = 0.246), and 86.4%/86.2%/80.0% at day 14 (P = 0.721). No serious adverse events were reported. Azvudine may be comparable to nirmatrelvir/ritonavir and molnupiravir in adult patients with mild-to-moderate COVID-19 regarding time to NANC, hospital stay, and AEs.
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Azidas , COVID-19 , Citidina/análogos & derivados , Desoxicitidina/análogos & derivados , Hidroxilaminas , Lactamas , Leucina , Nitrilos , Prolina , Ritonavir , Adulto , Humanos , Estudios Retrospectivos , Ritonavir/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Antivirales/uso terapéuticoRESUMEN
BACKGROUND: Azvudine has clinical benefits and acceptable safety against COVID-19, including in patients with comorbidities, but there is a lack of available data for its use in older adult patients. This study explored the effectiveness and safety of azvudine in older adults with mild or moderate COVID-19. METHODS: This retrospective cohort study included patients aged ≥80 diagnosed with COVID-19 at the Central Hospital of Shaoyang between October and November 2022. According to the therapies they received, the eligible patients were divided into the azvudine, nirmatrelvir/ritonavir, and standard-of-care (SOC) groups. The outcomes were the proportion of patients progressing to severe COVID-19, time to nucleic acid negative conversion (NANC), and the 5-, 7-, 10-, and 14-day NANC rates from admission. RESULTS: The study included 55 patients treated with azvudine (n = 14), nirmatrelvir/ritonavir (n = 18), and SOC (n = 23). The median time from symptom onset to NANC of the azvudine, nirmatrelvir/ritonavir, and SOC groups was 14 (range, 6-25), 15 (range, 11-24), and 19 (range, 18-23) days, respectively. The median time from treatment initiation to NANC of the azvudine and nirmatrelvir/ritonavir groups was 8 (range, 4-20) and 9 (range, 5-16) days, respectively. The median length of hospital stay in the three groups was 10.5 (range, 5-23), 13.5 (range, 10-21), and 17 (range, 10-23) days, respectively. No treatment-related adverse events or serious adverse events were reported. CONCLUSION: Azvudine showed satisfactory effectiveness and acceptable safety in older adults with mild or moderate COVID-19. Therefore, azvudine could be a treatment option for this special patient population.
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Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Anciano , Humanos , Antivirales/efectos adversos , Estudios Retrospectivos , RitonavirRESUMEN
Osteoarthritis (OA) is a chronic degenerative joint disease characterized by cartilage degeneration and subchondral bone remodelling. Currently, conservative treatment strategies cannot effectively alleviate the progression of OA. In this study, we used computer network analysis to show that Nitisinone (NTBC) is closely related to extracellular matrix degradation in OA and mainly interferes with the TNF-α signaling pathway. NTBC is an orphan drug used to treat hereditary type I tyrosinemia by altering phenylalanine/tyrosine metabolic flow. In this study, we found that NTBC effectively reduced chondrocyte inflammation and extracellular matrix degradation induced by TNF-α. Mechanistically, NTBC inhibited the cGAS/STING signaling pathway and reduced activation of the STING-dependent NF-κB pathway to alleviate inflammation. In addition, NTBC inhibited osteoclastogenesis and delayed the occurrence of subchondral bone remodelling. In mice with ACLT-induced osteoarthritis, intra-articular injection of NTBC significantly reduced cartilage degradation and subchondral bone remodelling. NTBC showed impressive therapeutic efficacy as a potential pharmaceutical intervention for the treatment of OA.
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Cartílago Articular , Ciclohexanonas , Nitrobenzoatos , Osteoartritis , Ratones , Animales , FN-kappa B/metabolismo , Osteogénesis , Factor de Necrosis Tumoral alfa/metabolismo , Osteoartritis/tratamiento farmacológico , Osteoartritis/metabolismo , Inflamación/tratamiento farmacológico , CondrocitosRESUMEN
Background: Massive hemoptysis during pregnancy is very rare. Dieulafoy's disease is one of the causes of massive hemoptysis. There are few reports of ECMO use to treat massive hemoptysis during pregnancy. Findings: We report for the first time a patient with Dieulafoy's disease diagnosed at 29 weeks of pregnancy. The patient's hemoptysis occurred rapidly with large volumes. The bleeding amount reached 500 ml within half an hour, with the development of asphyxia and respiratory and cardiac arrest due to a blood clot blocking the airway. After successful cardiopulmonary resuscitation, the ventilator could not maintain effective ventilation. Emergency establishment of VV-ECMO was performed to maintain oxygen, and hemostasis was successfully achieved by performing bronchial artery embolization twice. We successfully cleaned blood clots in the airway four times by freezing and using a foreign body retrieval basket with an electronic bronchoscope. At the same time, small and smooth nodular lesions were found under bronchoscopy, and blood vessels with a diameter of 1.5 mm were found under Doppler mode with an ultrasonic bronchoscope, which was consistent with a diagnosis of Dieulafoy's disease. VV-ECMO was successfully stopped on the 3rd day of the disease course, tracheal intubation was successfully removed on the 5th day of the disease course, and the patient was discharged with no complications on the 16th day of the disease course.
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Osteoporosis, which manifests as reduced bone mass and deteriorated bone quality, is common in the elderly population. It is characterized by persistent elevation of macrophage-associated inflammation and active osteoclast bone resorption. Currently, the roles of intracellular metabolism in regulating these processes remain unclear. In this study, we initially performed bioinformatics analysis and observed a significant increase in the proportion of M1 macrophages in bone marrow with aging. Further metabolomics analysis demonstrated a notable reduction in the expression of carnitine metabolites in aged macrophages, while carnitine was not detected in osteoclasts. During the differentiation process, osteoclasts took up carnitine synthesized by macrophages to regulate their own activity. Mechanistically, carnitine enhanced the function of Nrf2 by inhibiting the Keap1-Nrf2 interaction, reducing the proteasome-dependent ubiquitination and degradation of Nrf2. In silico molecular ligand docking analysis of the interaction between carnitine and Keap1 showed that carnitine binds to Keap1 to stabilize Nrf2 and enhance its function. In this study, we found that the decrease in carnitine levels in aging macrophages causes overactivation of osteoclasts, ultimately leading to osteoporosis. A decrease in serum carnitine levels in patients with osteoporosis was found to have good diagnostic and predictive value. Moreover, supplementation with carnitine was shown to be effective in the treatment of osteoporosis.
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Resorción Ósea , Osteoporosis , Humanos , Anciano , Osteogénesis/genética , Proteína 1 Asociada A ECH Tipo Kelch/genética , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Carnitina/metabolismo , Transducción de Señal , Osteoclastos/metabolismo , Macrófagos/metabolismo , Resorción Ósea/complicaciones , Resorción Ósea/metabolismo , Osteoporosis/tratamiento farmacológico , Osteoporosis/genética , Ligando RANK/farmacologíaRESUMEN
Indole is a very important signal molecule which plays multiple regulatory roles in many physiological and biochemical processes of bacteria, but up to now, the reasons for its wide range of functions have not been revealed. In this study, we found that indole inhibits the motility, promotes glycogen accumulation and enhances starvation resistance of Escherichia coli. However, the regulatory effects of indole became insignificant while the global csrA gene was mutated. To reveal the regulatory relationship between indole and csrA, we studied the effects of indole on the transcription level of csrA, flhDC, glgCAP and cstA, and also the sensing of the promoters of the genes on indole. It was found that indole inhibited the transcription of csrA, and only the promoter of the csrA gene can sense indole. Namely, indole indirectly regulated the translation level of FlhDC, GlgCAP and CstA. These data indicates that indole regulation is related with the regulation of CsrA, which may throw light on the regulation mechanism research of indole.
Asunto(s)
Proteínas de Escherichia coli , Escherichia coli , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Proteínas de Unión al ARN/química , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Indoles/farmacología , Regulación Bacteriana de la Expresión Génica , Proteínas Represoras/genética , Proteínas Represoras/metabolismoRESUMEN
Laccase is a multicopper oxidoreductase enzyme that can oxidize organics such as phenolic compounds. Laccases appear to be unstable at room temperature, and their conformation often changes in a strongly acidic or alkaline environment, making them less effective. Therefore, rationally linking enzymes with supports can effectively improve the stability and reusability of native enzymes and add important industrial value. However, in the process of immobilization, many factors may lead to a decrease in enzymatic activity. Therefore, the selection of a suitable support can ensure the activity and economic utilization of immobilized catalysts. Metal-organic frameworks (MOFs) are porous and simple hybrid support materials. Moreover, the characteristics of the metal ion ligand of MOFs can enable a potential synergistic effect with the metal ions of the active center of metalloenzymes, enhancing the catalytic activity of such enzymes. Therefore, in addition to summarizing the biological characteristics and enzymatic properties of laccase, this article reviews laccase immobilization using MOF supports, as well as the application prospects of immobilized laccase in many fields.