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BACKGROUND: Early detection of high-risk nasopharyngeal carcinoma (NPC) recurrence is essential. We created a machine learning-derived prognostic signature (MLDPS) by combining three machine learning (ML) models to predict progression-free survival (PFS) in patients with non-metastatic NPC. METHODS: A cohort of 653 patients with non-metastatic NPC was divided into a training (n = 457) and validation (n = 196) dataset (7:3 ratio). The study included clinicopathological characteristics, hematologic markers, and MRI findings in three machine learning models-random forest (RF), extreme gradient boosting (XGBoost), and least absolute shrinkage and selection operator (LASSO)-to predict progression-free survival (PFS). A Venn diagram identified the overlapping signatures from the three ML algorithms. Cox proportional hazard analysis determined the MLDPS for PFS. RESULTS: The RF, XGBoost, and LASSO algorithms identified six consensus factors from the 33 signatures. Cox proportional hazards analysis showed that the MLDPS includes age, lymphocyte count, number of positive lymph nodes, and regional lymph node density. Additionally, MLDPS effectively stratified prognosis, with low-risk individuals showing better PFS than high-risk individuals (p < 0.001). CONCLUSION: MLDPS, based on clinicopathological characteristics, hematologic markers, and MRI findings, is crucial for guiding clinical management and personalizing treatments for patients with non-metastatic NPC.
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RATIONALE AND OBJECTIVES: Accurate assessment of lymphovascular invasion (LVI) in invasive breast cancer (IBC) plays a pivotal role in tailoring personalized treatment plans. This study aimed to investigate habitats-based spatial distributions to quantitatively measure tumor heterogeneity on multiparametric magnetic resonance imaging (MRI) scans and assess their predictive capability for LVI in patients with IBC. MATERIALS AND METHODS: In this retrospective cohort study, we consecutively enrolled 241 women diagnosed with IBC between July 2020 and July 2023 and who had 1.5 T/T1-weighted images, fat-suppressed T2-weighted images, and dynamic contrast-enhanced MRI. Habitats-based spatial distributions were derived from the gross tumor volume (GTV) and gross tumor volume plus peritumoral volume (GPTV). GTV_habitats and GPTV_habitats were generated through sub-region segmentation, and their performances were compared. Subsequently, a combined nomogram was developed by integrating relevant spatial distributions with the identified MR morphological characteristics. Diagnostic performance was compared using receiver operating characteristic curve analysis and decision curve analysis. Statistical significance was set at p < 0.05. RESULTS: GPTV_habitats exhibited superior performance compared to GTV_habitats. Consequently, the GPTV_habitats, diffusion-weighted imaging rim signs, and peritumoral edema were integrated to formulate the combined nomogram. This combined nomogram outperformed individual MR morphological characteristics and the GPTV_habitats index, achieving area under the curve values of 0.903 (0.847 -0.959), 0.770 (0.689 -0.852), and 0.843 (0.776 -0.910) in the training set and 0.931 (0.863 -0.999), 0.747 (0.613 -0.880), and 0.849 (0.759 -0.938) in the validation set. CONCLUSION: The combined nomogram incorporating the GPTV_habitats and identified MR morphological characteristics can effectively predict LVI in patients with IBC.
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Tumor-specific T cells (TSTs) are essential components for the success of personalized tumor-infiltrating lymphocyte (TIL)-based adoptive cellular therapy (ACT). Therefore, the selection of a common biomarker for screening TSTs in different tumor types, followed by ex vivo expansion to clinical number levels can generate the greatest therapeutic effect. However, studies on shared biomarkers for TSTs have not been realized yet. The present review summarizes the similarities and differences of a number of biomarkers for TSTs in several tumor types studied in the last 5 years, and the advantages of combining biomarkers. In addition, the review discusses the possible shortcomings of current biomarkers and highlights strategies to identify TSTs accurately using intercellular interactions. Finally, the development of TSTs in personalized TIL-based ACT for broader clinical applications is explored.
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Neoplasias , Linfocitos T , Humanos , Recuento de Linfocitos , Neoplasias/terapia , Biomarcadores , Linfocitos Infiltrantes de TumorRESUMEN
BACKGROUND: The cyclooxygenase-2 (COX-2) selective inhibitor parecoxib is widely used in the treatment of pain and inflammation. Parecoxib has been adopted for use for postoperative analgesia following a range of surgical procedures (orthopedic, general, gynecological, and dental surgery). Total knee or total hip arthroplasty (THA) surgery is mostly done in older patients, so postoperative analgesics need to be used more carefully, and the safety and efficacy of parecoxib in this type of surgery need to be further verified. The aim of this study was to investigate the effects of parecoxib on patient safety, cumulative morphine consumption and was at 24 and 48 hours in the analgesic treatment of total knee or THA for meta-analysis and systematic review, with few studies in this area so far. METHODS: We searched the Online Database Cochrane Library, PubMed, Web of Science, EMBASE, and CBM (SinoMed), CNKI, VIP, WANFANG up to January 2021. According to the value of I2, the random-effect model or fixed-effect model was supposed to combine data from studies, respectively. Publication bias was assessed through funneling plot and Beggs test. Review Manager 5.3 and Stata 16.0 software were applied to perform the statistical analyses. RESULTS: Eleven RCTs which involved 1690 participants were included in this study. The meta-analysis indicated parecoxib sodium could not significantly reduce the incidence of adverse events after total knee or THA compared with placebo. There was no statistical significance in incidence of nausea and vomiting. 24 hours resting VAS score was statistically significant between the group. The 48-hour resting VAS scores did not indicate a significant difference between the groups. CONCLUSION: Parecoxib can reduce the incidence of adverse events after total knee or total hip surgery to some extent but cannot reduce the incidence of nausea and vomiting. Twenty-four hour postoperative analgesia is better than placebo, but 48 hours after operation analgesia is the same as placebo.
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Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Anciano , Analgésicos/uso terapéutico , Analgésicos Opioides , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Humanos , Isoxazoles , Morfina , Náusea/etiología , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Vómitos/etiologíaRESUMEN
Pancreatic beta cells are highly susceptible to oxidative stress, which plays a crucial role in diabetes outcomes. Progress has been slow to identify molecules that could be utilized to enhance cell survival and function under oxidative stress. Itaconate, a byproduct of the tricarboxylic acid cycle, has both anti-inflammatory and antioxidant properties. The effects of itaconate on beta cells under oxidative stress are relatively unknown. We explored the effects of 4-octyl itaconate-a cell-permeable derivative of itaconate-on MIN6 (a beta cell model) under oxidative stress conditions caused by hypoxia, along with its mechanism of action. Treatment with 4-OI reversed hypoxia-induced cell death, reduced ROS production, and inhibited cell death pathway activation and inflammatory cytokine secretion in MIN6 cells. The 4-OI treatment also suppressed lactate dehydrogenase A (LDHA)activity, which increases under hypoxia. Treatment of cells with the ROS scavenger NAC and LDHA-specific inhibitor FX-11 reproduced the beneficial effects of 4-OI on MIN6 cell viability under oxidative stress conditions, confirming its role in regulating ROS production. Conversely, overexpression of LDHA reduced the beneficial effects exerted by 4-OI on cells. Our findings provide a strong rationale for using 4-OI to prevent the death of MIN6 cells under oxidative stress.
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Antioxidantes , Estrés Oxidativo , Antioxidantes/metabolismo , Antioxidantes/farmacología , Citocinas/metabolismo , Humanos , Hipoxia , Lactato Deshidrogenasa 5 , Especies Reactivas de Oxígeno/metabolismo , SuccinatosAsunto(s)
Enema Opaco/métodos , Enfermedad de Hirschsprung , Intestino Grueso/diagnóstico por imagen , Intensificación de Imagen Radiográfica/métodos , Radiografía Abdominal/métodos , Colectomía/métodos , Medios de Contraste/farmacología , Enfermedad de Hirschsprung/diagnóstico , Enfermedad de Hirschsprung/fisiopatología , Enfermedad de Hirschsprung/cirugía , Humanos , Recién Nacido , Resultado del TratamientoRESUMEN
OBJECTIVE: To assess the effects of two different nutritional mode on the occurrence of ventilator-associated pneumonia (VAP) in patients on mechanical ventilation. METHODS: 70 patients admitted to the ICU and under mechanical ventilation, were randomly divided into the nasointestinal tube group and nasogastric tube group. Patients from both groups received enteral nutrition, using the same nutritional agent, through intubation. The duration of stay in the ICU, duration of mechanical ventilation, incidence of VAP, nutritional state, and survival of the intestinal tract were compared between the two groups. RESULTS: The duration of stay in the ICU, duration of mechanical ventilation and incidence of VAP in the nasointestinal tube group was lower than that in the nasogastric tube group (P<0.05). There was an increase in the levels of prealbumin and transferrin in the nasointestinal tube group (P<0.05). However, there were no obvious difference in the nasogastric tube group (P<0.05). The incidence of abdominal distension, diarrhea, regurgitation, aspiration, and hyperglycemia in the nasointestinal tube group was much lower than that in the nasogastric tube group (P < 0.05). CONCLUSION: This study showed that enteral nutrition delivery using a nasointestinal way can effectively reduce the incidence of VAP and improve the nutritional status of patients under mechanical ventilation.
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Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Enfermedades Intestinales , Intestinos , Diagnóstico Diferencial , Motilidad Gastrointestinal , Humanos , Recién Nacido , Enfermedades Intestinales/congénito , Enfermedades Intestinales/diagnóstico , Enfermedades Intestinales/fisiopatología , Enfermedades Intestinales/cirugía , Intestinos/anomalías , Intestinos/diagnóstico por imagen , Intestinos/fisiopatología , Intestinos/cirugía , Laparotomía/métodos , Masculino , Intensificación de Imagen Radiográfica , Resultado del TratamientoRESUMEN
A pH-responsive threadlike micellar system was developed by mixing alkyl bis(2-hydroxyethyl)methylammonium chloride (EO12) and trans-o-coumaric acid (tOCA). The rheological response of this system to pH is unusual in that it has viscoelasticity at both high and low pH levels, while it shows water-like behaviors at medium pH. Cryogenic transmission electron microscopy (Cryo-TEM) images confirmed the presence of TLMs at pH 3.5 and pH 9.8. This system also had DR (drag reduction) capability at low and high pH. The unusual rheological and micellar responses of this system to pH are caused by the dual pK(a)'s of tOCA. (1)H NMR and zeta potential results support this hypothesis.
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A photoresponsive micellar solution is developed as a promising working fluid for district heating/cooling systems (DHCs). It can be reversibly switched between a drag reduction (DR) mode and an efficient heat transfer (EHT) mode by light irradiation. The DR mode is advantageous during fluid transport, and the EHT mode is favored when the fluid passes through heat exchangers. This smart fluid is an aqueous solution of cationic surfactant oleyl bis(2-hydroxyethyl)methyl ammonium chloride (OHAC, 3.4 mM) and the sodium salt of 4-phenylazo benzoic acid (ACA, 2 mM). Initially, ACA is in a trans configuration and the OHAC/ACA solution is viscoelastic and exhibits DR (of up to 80% relative to pure water). At the same time, this solution is not effective for heat transfer. Upon UV irradiation, trans-ACA is converted to cis-ACA, and in turn, the solution is converted to its EHT mode (i.e., it loses its viscoelasticity and DR) but it now has a heat-transfer capability comparable to that of water. Subsequent irradiation with visible light reverts the fluid to its viscoelastic DR mode. The above property changes are connected to photoinduced changes in the nanostructure of the fluid. In the DR mode, the OHAC/trans-ACA molecules assemble into long threadlike micelles that impart viscoelasticity and DR capability to the fluid. Conversely, in the EHT mode the mixture of OHAC and cis-ACA forms much shorter cylindrical micelles that contribute to negligible viscoelasticity and effective heat transfer. These nanostructural changes are confirmed by cryo-transmission electron microscopy (cryo-TEM), and the photoisomerization of trans-ACA and cis-ACA is verified by (1)H NMR.
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Drag-reducing (DR) surfactant fluids based on threadlike micelles are known to suffer from poor heat-transfer capabilities. Accordingly, the use of these fluids is limited to recirculating systems in which heat exchange is not important. Here, we show for the first time that light-responsive threadlike micelles can offer a potential solution to the above problem. The fluids studied here are composed of the cationic surfactant Ethoquad O/12 PG (EO12) and the sodium salt of trans-ortho-methoxycinnamic acid (OMCA). Initially, these fluids contain numerous threadlike micelles and, in turn, are strongly viscoelastic and effective at reducing drag (up to 75% DR). Upon exposure to UV light, OMCA is photoisomerized from trans to cis. This causes the micelles to shorten considerably, as confirmed by cryo-transmission electron microscopy (cryo-TEM). Because of the absence of long micelles, the UV-irradiated fluid shows lower viscoelasticity and much lower DR properties; however, its heat-transfer properties are considerably superior to the initial fluid. Thus, our study highlights the potential of switching off the DR (and in turn enhancing heat-transfer) at the inlet of a heat exchanger in a recirculating system. While the fluids studied here are not photoreversible, an extension of the above concept would be to subsequently switch on the DR again at the exit of the heat exchanger, thus ensuring an ideal combination of DR and heat-transfer properties.
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Drag reduction effectiveness of two dilute quaternary ammonium surfactant aqueous solutions with different pairs of mixed aromatic counterions was investigated along with their micellar nanostructures revealed by cryo-TEM imaging, zeta potential, particle size, and (1)H NMR measurements. Certain combinations of aromatic counterion mixtures showed significant synergistic effects. They dramatically improved drag reduction effectiveness relative to either single aromatic counterion. Using mixed aromatic counterions with different sizes and binding abilities, the effective drag reducing temperature range can be significantly expanded and higher shear stress stability can be achieved. The synergistic effects are believed to be induced by increased degree of branching in the surfactant micellar networks as shown by cryo-TEM images.
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OBJECTIVE: The temporal and spatial features of body segmental movements of the head, trunk, thigh, shank and foot in response to a fast speed postural disturbance were compared among four age groups. It was hypothesized that the upper body movement was minimized in the healthy young adults, but was augmented in the older adults. DESIGN: Repeated measures design with 12 experimental conditions. BACKGROUND: It is not well understood yet why the elderly fall more than the young. In studies of locomotion and active balance tasks, the head position has been suggested as a reference frame for controlling dynamic equilibrium. This study was aimed at examining: (1) whether or not this reference frame would exist during involuntary balance tasks, which are most likely related to accidental falls in the elderly; and (2) how would the stability of this reference frame change with age. METHODS: Thirty-six healthy subjects of four age groups (20-70 + yr of age) participated in this study. Postural perturbation was introduced by a moving platform. The sagittal plane kinematics of five body segments was directly measured using Integrated Kinematic Sensors. RESULTS: Compared to the lower limb movement, the upper body movement, especially the head, was minimal (less than 7 degrees ) in the young adults (age group 1), and was largest (about 14 degrees ) in the older subjects (age groups 2, 3 and 4). Moreover, the maximum range of motion of the older adults was found to be positively correlated not only to the height of the segment, but also to the timings of the movements, while the young adults showed no correlation between range of motion and the timings of the movement. CONCLUSIONS: The findings suggested that the young adults indeed stabilized their upper body as a reference frame for maintaining postural balance. In contrast, this reference frame was not stabilized well in the older adults. In compensation, the older adults adopted a more rigid movement strategy, compared to a more flexible movement strategy in the young. All these changes would lead the older subjects to be less tolerable to postural disturbances and more susceptible to falls than the young subjects.