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The metal-organic framework (MOF) constructed from [Co4Pz8] clusters (Pz = pyrazolate) and 1,3,5-tris(pyrazolate-4-yl) benzene (BTP3-) ligands was structurally predicted many years ago, and expected to be a promising candidate for various applications owing to its unique clusters and highly open 3D framework structure. However, this MOF has not been experimentally prepared yet, despite extensive efforts were made. In this work, we present the successful construction of this MOF, hereinafter referred to as BUT-124(Co), by adopting a two-step synthesis strategy, involving the initial construction of a template framework (BUT-124(Cd)) followed by a post-synthetic metal metathesis process. The effects of various cobalt sources and solvents were systematically investigated, and an innovative stepwise metathesis strategy was employed to optimize the exchange rates and the porosity of the material. BUT-124(Co) demonstrates high catalytic activity in the oxygen evolution reaction (OER), achieving a competitive performance with an overpotential of 393 mV at a current density of 10 mA cm-2, and also affords remarkable long-term stability during potentiostatic electrolysis in 1 M KOH solution, surpassing the durability of many benchmark catalysts. This work not only introduces a novel MOF material with promising properties but also exemplifies a strategic synthesis approach for pyrazolate-based MOFs, paving the way for advancements in diverse application fields.
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Sulfur hexafluoride (SF6) is extensively employed in the power industry. However, its emissions significantly contribute to the greenhouse effect. The direct recovery of high purity SF6 from industrial waste gases would benefit its sustainable use, yet this represents a considerable challenge. Herein, we report the enrichment of SF6 from SF6/N2 mixtures via adsorptive separation in a stable Co(II)-pyrazolate MOF BUT-53 (BUT: Beijing University of Technology), which features dynamic molecular traps. BUT-53 exhibits an excellent SF6 adsorption uptake of 2.82 mmol/g at 0.1 bar and 298 K, as well as an unprecedented SF6/N2 (10:90) selectivity of 2485. Besides, the remarkable SF6/N2 selectivity of BUT-53 enables recovery of high purity (>99.9%) SF6 from a low concentration (10%) mixture through a breakthrough experiment. The excellent SF6/N2 separation efficiency was also well maintained under humid conditions (RH = 90%) over multiple cycles. Molecular simulation, single-crystal diffraction, and adsorption kinetics studies elucidate the associated adsorption mechanism and water tolerance.
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BACKGROUND: Recent research highlights the importance of muscular strength as a key factor in physical fitness, a strong indicator of overall mortality risk, and a vital target for preventing chronic diseases. This study used a proteome-wide Mendelian randomization analysis plus colocalization analysis for low hand grip strength to explore potential therapeutic targets for muscle weakness. METHODS: We conducted two two-sample Mendelian randomization analyses from four cohorts to identify and validate the causal relationship between plasma proteins and low grip strength. We also employed bidirectional Mendelian randomization analysis with Steiger filtering, Bayesian co-localization, and phenotype scanning to detect reverse causality, thereby consolidating our Mendelian randomization findings. Downstream analyses were also undertaken of identified proteins, including knockout models, enrichment analyses, and protein-protein interaction networks. Finally, we assessed the druggability of the identified proteins. RESULTS: At Bonferroni significance (P < 6.82 × 10-5), Mendelian randomization analysis revealed that three proteins were causally associated with low grip strength. Increased MGP (OR = 0.85) and HP (OR = 0.96) decreased the risk of low grip strength, whereas elevated ART4 (OR = 1.06) increased the risk of low grip strength. None of the three proteins had reverse causality with low grip strength. Bayesian co-localization suggested that MGP shared the same variant with low grip strength (coloc.abf-PPH4 = 0.826). Further downstream analyses showed that MGP, which is highly expressed in musculoskeletal system, is a potential novel target for muscle weakness. CONCLUSIONS: The proteome-wide Mendelian randomization investigation identified three proteins associated with the risk of muscle weakness. MGP, HP, and ART4 deserve further investigation as potential therapeutic targets for muscle weakness.
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Minimization of cadmium (Cd) accumulation in wheat grain (Triticum aestivum L.) is an important way to prevent Cd hazards to humans. However, little is known about the mechanisms of varietal variation of Cd accumulation in wheat grain. This study explores the physiological mechanisms of Cd bioaccumulation through field and hydroponic experiments on two wheat varieties of low-Cd-accumulating variety (L-6331) and high-Cd-accumulating variety (H-6049). Field study showed that average Cd accumulative rates in spikes of H-6049 were 1.57-fold of L-6331 after flowering, ultimately grain-Cd of H-6049 was 1.70-fold of L-6331 in Cd-contaminated farmland. The hydroponic experiment further confirmed that more vegetative tissues of L-6331 were involved in the remobilization of Cd, which jointly mitigated the process of Cd loaded to grains when leaf-cutting conducted after Cd stress. Additionally, the L1 and N1 of L-6331 play an especially important role in regulating Cd remobilization, and the larger EVB areas in N1 have the morphological feature that facilitates the transfer of Cd to L1. Overall results implied that low-Cd-accumulating variety initiated more trade-offs of reproductive growth and Cd remobilizatoin under Cd-stress after flowering compared with high-Cd-accumulating variety, and provided new insights into the processes of Cd loaded into wheat grains among different varieties.
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Cadmio , Contaminantes del Suelo , Triticum , Triticum/metabolismo , Triticum/crecimiento & desarrollo , Cadmio/metabolismo , Contaminantes del Suelo/metabolismo , Bioacumulación , Reproducción , Grano Comestible/metabolismo , Grano Comestible/crecimiento & desarrolloRESUMEN
BACKGROUND: It remains unclear whether the time interval between total thyroidectomy and radioactive iodine (RAI) therapy influences clinical outcomes in papillary thyroid carcinoma (PTC). This study aims to evaluate the impact of the timing to initiate RAI therapy on the response in PTC patients. METHODS: We retrospectively included 405 patients who underwent total thyroidectomy and subsequent RAI therapy at two tertiary hospitals in southwest China. Patients were categorized into two groups based on the interval between thyroidectomy and initial RAI therapy, that is, an early group (interval ≤90 days, n â =â 317) and a delayed group (interval >90 days, n â =â 88). Responses to RAI therapy were classified as excellent, indeterminate, biochemical incomplete, or structural incomplete. Univariate and multivariate analyses were conducted to identify factors associated with a nonexcellent response. RESULTS: Excellent responses were observed in 77.3% of the early group and 83.0% of the delayed group ( P â =â 0.252). No significant impact of RAI therapy timing was also observed across all American Thyroid Association risk classification categories. These findings persisted when patients were analyzed separately according to RAI dose (intermediate-dose group: 3.7 GBq [ n â =â 332]; high-activity group: ≥5.5 GBq [ n â =â 73]), further subdivided by the timing of RAI therapy. Multivariate analysis identified lymph node dissection, RAI dose, and stimulated thyroglobulin as independent risk factors for excellent response ( P â <â 0.05). CONCLUSION: The timing of initial RAI therapy following surgery did not significantly affect outcomes in patients with PTC.
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Radioisótopos de Yodo , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , Radioisótopos de Yodo/uso terapéutico , Estudios Retrospectivos , Masculino , Femenino , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Persona de Mediana Edad , Cáncer Papilar Tiroideo/radioterapia , Cáncer Papilar Tiroideo/cirugía , Adulto , Resultado del Tratamiento , Factores de Tiempo , Tiroidectomía , Anciano , Carcinoma Papilar/radioterapia , Carcinoma Papilar/patología , Adulto Joven , AdolescenteRESUMEN
Lead (Pb) contamination in wheat grain is of great concern, especially in North China. Atmospheric deposition is a major contributor to Pb accumulation in wheat grain. Screening low Pb accumulating wheat varieties has been an effective method for addressing Pb contamination in wheat grain. However, identifying wheat varieties with low Pb accumulation based on foliar uptake of atmospheric Pb has been neglected. Therefore, two field trials with distinct atmospheric Pb deposition were conducted to screen for stable varieties with low Pb accumulation. It was verified that YB700 and CH58, which have high thousand-grain weights and stable low Pb accumulation in field 1 (0.19 and 0.13 mg kg-1) and field 2 (0.17 and 0.20 mg kg-1), respectively, were recommended for cultivation in atmospheric Pb contaminated farmlands in North China. Furthermore, indoor experiments were conducted to investigate Pb uptake by the roots and leaves of different wheat varieties. Our findings indicate that Pb accumulation in different wheat varieties is primarily influenced by foliar Pb uptake rather than root Pb uptake. Interestingly, there was a positive correlation (p < 0.05) between the Pb concentrations in leaves and the stomatal width and trichome length of the adaxial epidermal surface. Additionally, there is a positive correlation (p < 0.01) between the Pb concentration in the wheat grain and trichome length. In conclusion, the screening of wheat varieties with narrower stomatal widths or shorter trichomes based on foliar uptake pathways is an effective strategy for ensuring food safety in areas contaminated by atmospheric Pb.
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Plomo , Hojas de la Planta , Contaminantes del Suelo , Triticum , Triticum/metabolismo , Plomo/metabolismo , Hojas de la Planta/metabolismo , China , Contaminantes del Suelo/metabolismo , Contaminantes del Suelo/análisis , Monitoreo del Ambiente/métodos , Contaminantes Atmosféricos/análisisRESUMEN
This study aims to explore the potential mechanism of action in the intervention of acute lung injury(ALI) based on the blood entry components of Ganke Granules in rats and in conjunction with network pharmacology, molecular docking, and animal experimental validation. The blood entry components of Ganke Granules in rats were imported into the SwissTargetPrediction platform to predict drug targets, and ALI-related targets were collected from the disease database. Intersections were taken, and protein-protein interaction(PPI) networks were constructed to screen the core targets, followed by Gene Ontology(GO) functional and Kyoto encyclopedia of genes and gnomes(KEGG) pathway enrichment analyses. A "blood entry components-target-pathway-disease" network was constructed, and the core components for disease intervention based on their topological parameters were screened. Molecular docking was used to predict the binding ability of the core components to key targets. The key targets of Ganke Granules in the intervention of ALI were verified by the lipopolysaccharide(LPS)-induced ALI mouse model. Through PPI topological parameter analysis, the top six key targets of STAT3, SRC, HSP90AA1, MAPK3, HRAS, and MAPK1 related to ALI were obtained. GO functional analysis showed that it was mainly related to ERK1 and ERK2 cascade, inflammatory response, and response to LPS. KEGG analysis showed that the main enrichment pathways were MAPK, neutrophil extracellular trap(NET) formation, and so on. Six core components(schizantherin B, schisandrin, besigomsin, harpagoside, isotectorigenin, and trachelanthamine) were filtered out by the "blood entry components-target-pathway-disease" network based on the analysis of topological parameters. Molecular docking results showed that the six core components and Tectoridin with the highest content in the granules had a high affinity with the key targets of MAPK3, SRC, MAPK1, and STAT3. In vivo experiment results showed that compared with the model group, Ganke Granules could effectively alleviate LPS-induced histopathological injury in the lungs of mice and reduce the percentage of inflammatory infiltration. The total protein content, nitric oxide(NO) level, myeloperoxidase(MPO) content, tumor necrosis factor-α(TNF-α), gamma interferon(IFN-γ), interleukin-1ß(IL-1ß), interleukin-6(IL-6), vascular endothelial growth factor(VEGF), and chemokine(C-X-C motif) ligand 1(CXCL1) chemokines in bronchoalveolar lavage fluid(BALF) were decreased, and the expression levels of lymphocyte antigen 6G(Ly6G), citrullinated histones 3(Cit-H3), and phosphorylated proteins SRC, ERK1/2, and STAT3 in lung tissue were significantly down-regulated. In conclusion, Ganke Granules could effectively inhibit the inflammatory response of ALI induced by LPS, protect lung tissue, regulate the release of inflammatory factors, and inhibit neutrophil infiltration and NET formation, and the mechanism of action may be related to inhibiting the activation of SRC/ERK1/2/STAT3 signaling pathway.
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Lesión Pulmonar Aguda , Medicamentos Herbarios Chinos , Simulación del Acoplamiento Molecular , Farmacología en Red , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Ratones , Ratas , Masculino , Mapas de Interacción de Proteínas , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Ratas Sprague-Dawley , HumanosRESUMEN
BACKGROUND: Frailty is recognized as a surrogate for physiological age and has been established as a valid and independent predictor of postoperative morbidity, mortality, and complications. Enhanced recovery after surgery (ERAS) can enhance surgical safety by minimizing stress responses in frail patients, enabling surgeons to discharge patients earlier. However, the question of whether and to what extent the frailty impacts the post-ERAS outcomes in older patients remains. MATERIALS AND METHODS: An evidence-based ERAS program was implemented in our center from January 2019. This is a prospective cohort study of patients aged ≥75 years who underwent open transforaminal lumbar interbody fusion (TLIF) for degenerative spine disease from April 2019 to October 2021. Frailty was assessed with the Fried frailty scale (FP scale), and patients were categorized as non/prefrail (FP 0-2) or frail (FP ≥ 3). The preoperative variables, operative data, postoperative outcomes, and follow-up information were compared between the two groups. Univariate and multivariate logistic regression analyses were used to identify risk factors for 90-day major complications and prolonged length of hospital stay after surgery. RESULTS: A total of 245 patients (age of 79.8±3.4 year) who had a preoperative FP score recorded and underwent scheduled TLIF surgery were included in the final analysis. Comparisons between nonfrail and prefrail/frail patients revealed no significant difference in age, sex, and surgery-related variables. Even after adjusting for multiple comparisons, the association between Fried frailty and ADL-dependency, IADL-dependency, and malnutrition remained significant. Preoperative frailty was associated with increased rates of postoperative adverse events. A higher CCI grade was an independent predictor for 90-day major complications, while Fried frailty and MNA-SF scores <12 were predictive of poor postoperative recovery. CONCLUSION: Frail older patients had more adverse post-ERAS outcomes after TLIF compared to non/prefrail older patients. Continued research and multidisciplinary collaboration will be essential to refine and optimize protocols for surgical care in frail older adults.
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Recuperación Mejorada Después de la Cirugía , Fragilidad , Vértebras Lumbares , Complicaciones Posoperatorias , Fusión Vertebral , Humanos , Anciano , Femenino , Masculino , Estudios Prospectivos , Fusión Vertebral/efectos adversos , Fragilidad/complicaciones , Anciano de 80 o más Años , Vértebras Lumbares/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Anciano Frágil , Tiempo de Internación/estadística & datos numéricos , Factores de Riesgo , Estudios de Cohortes , Resultado del TratamientoRESUMEN
In our previous study, a screening of a variety of lycotonine-type diterpenoid alkaloids were screened for cardiotonic activity revealed that lycoctonine had moderate cardiac effect. In this study, a series of structurally diverse of lycoctonine were synthesized by modifying on B-ring, D-ring, E-ring, F-ring, N-atom or salt formation on lycoctonine skeleton. We evaluated the cardiotonic activity of the derivatives by isolated frog heart, aiming to identify some compounds with significantly enhanced cardiac effects, among which compound 27 with a N-isobutyl group emerged as the most promising cardiotonic candidate. Furthermore, the cardiotonic mechanism of compound 27 was preliminarily investigated. The result suggested that the cardiotonic effect of compound 27 is related to calcium channels. Patch clamp technique confirmed that the compound 27 had inhibitory effects on CaV1.2 and CaV3.2, with inhibition rates of 78.52 % ± 2.26 % and 79.05 % ± 1.59 % at the concentration of 50 µM, respectively. Subsequently, the protective effect of 27 on H9c2 cells injury induced by cobalt chloride was tested. In addition, compound 27 can alleviate CoCl2-induced myocardial injury by alleviating calcium overload. These findings suggest that compound 27 was a new structural derived from lycoctonine, which may serve as a new lead compound for the treatment of heart failure.
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Aconitina/análogos & derivados , Alcaloides , Cardiotónicos , Cardiotónicos/farmacología , Aconitina/química , Alcaloides/farmacología , Alcaloides/química , Canales de Calcio , CalcioRESUMEN
BACKGROUND: Recent research showed that cross-notation magnitude knowledge of fractions and decimals was related to better performance in fraction arithmetic, but it remains unclear whether it made an independent contribution to fraction arithmetic longitudinally when other cognitive variables are considered. AIMS: To examine the extent to which children's earlier knowledge of cross-notation magnitude predicted subsequent performance in fraction addition and subtraction as well as fraction multiplication and division longitudinally. SAMPLE: Three hundred and fifty-four Chinese children (Mage = 112.1 months). METHODS: During the first wave of assessment, a range of cognitive abilities of children were measured, including within-notation fraction and decimal magnitude comparisons, whole-number arithmetic fluency, non-verbal intelligence, attentive behaviours, counting recall, word-level reading, and phonological awareness. Twelve months later, the same children were assessed again with two tasks of fraction arithmetic: fraction addition and subtraction as well as fraction multiplication and division. RESULTS AND CONCLUSIONS: Multiple linear regressions showed that within-notation fraction and decimal magnitude knowledge predicted fraction addition and subtraction longitudinally, after the effects of working memory, nonverbal intelligence, language skills, attentive behaviour, and whole-number arithmetic were controlled. Cross-notation magnitude knowledge made independent contributions to fraction addition and subtraction longitudinally beyond the influence of within-notation fraction and decimal magnitude knowledge and other covariates. However, within-notation fraction and decimal magnitude knowledge were not associated with fraction multiplication and division, whereas cross-notation magnitude knowledge remained a unique predictor. These findings suggest that it may be useful to incorporate cross-notation knowledge in the assessments of children's mathematics abilities and teaching.
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Conceptos Matemáticos , Matemática , Humanos , Masculino , Femenino , Niño , Estudios Longitudinales , Desarrollo Infantil/fisiología , ChinaRESUMEN
Reinforcement learning (RL) stands as one of the three fundamental paradigms within machine learning and has made a substantial leap to build general-purpose learning systems. However, using traditional electrical computers to simulate agent-environment interactions in RL models consumes tremendous computing resources, posing a significant challenge to the efficiency of RL. Here, we propose a universal framework that utilizes a photonic integrated circuit (PIC) to simulate the interactions in RL for improving the algorithm efficiency. High parallelism and precision on-chip optical interaction calculations are implemented with the assistance of link calibration in the hybrid architecture PIC. By introducing similarity information into the reward function of the RL model, PIC-RL successfully accomplishes perovskite materials synthesis task within a 3472-dimensional state space, resulting in a notable 56% improvement in efficiency. Our results validate the effectiveness of simulating RL algorithm interactions on the PIC platform, highlighting its potential to boost computing power in large-scale and sophisticated RL tasks.
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PURPOSE: This study aimed to develop a predictive model for prolonged length of hospital stay (pLOS) in elderly patients undergoing lumbar fusion surgery, utilizing multivariate logistic regression, single classification and regression tree (hereafter, "classification tree") and random forest machine-learning algorithms. METHODS: This study was a retrospective review of a prospective Geriatric Lumbar Disease Database. The primary outcome measure was pLOS, which was defined as the LOS greater than the 75th percentile. All patients were grouped as pLOS group and non-pLOS. Three models (including logistic regression, single-classification tree and random forest algorithms) for predicting pLOS were developed using training dataset and internal validation using testing dataset. Finally, online tool based on our model was developed to assess its validity in the clinical setting (external validation). RESULTS: The development set included 1025 patients (mean [SD] age, 72.8 [5.6] years; 632 [61.7%] female), and the external validation set included 175 patients (73.2 [5.9] years; 97[55.4%] female). Multivariate logistic analyses revealed that older age (odds ratio [OR] 1.06, p < 0.001), higher BMI (OR 1.08, p = 0.002), number of fused segments (OR 1.41, p < 0.001), longer operative time (OR 1.02, p < 0.001), and diabetes (OR 1.05, p = 0.046) were independent risk factors for pLOS in elderly patients undergoing lumbar fusion surgery. The single-classification tree revealed that operative time ≥ 232 min, delayed ambulation, and BMI ≥ 30 kg/m2 as particularly influential predictors for pLOS. A random forest model was developed using the remaining 14 variables. Intraoperative EBL, operative time, delayed ambulation, age, number of fused segments, BMI, and RBC count were the most significant variables in the final model. The predictive ability of our three models was comparable, with no significant differences in AUC (0.73 vs. 0.71 vs. 0.70, respectively). The logistic regression model had a higher net benefit for clinical intervention than the other models. The nomogram was developed, and the C-index of external validation for PLOS was 0.69 (95% CI, 0.65-0.76). CONCLUSION: This investigation produced three predictive models for pLOS in elderly patients undergoing lumbar fusion surgery. The predictive ability of our three models was comparable. Logistic regression model had a higher net benefit for clinical intervention than the other models. Our predictive model could inform physicians about elderly patients with a high risk of pLOS after surgery.
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Nomogramas , Humanos , Anciano , Estudios Prospectivos , Tiempo de Internación , Estudios Retrospectivos , Factores de RiesgoRESUMEN
STUDY DESIGN: A retrospective study. OBJECTIVE: To compare the mini nutritional assessment-short form (MNA-SF), geriatric nutritional risk index, prognostic nutritional index (PNI), and preoperative serum albumin level as predictors of postoperative adverse events (AEs) in degenerative spine deformity (DSD) patients. SUMMARY OF BACKGROUND DATA: Although various nutritional screening tools have been well evaluated in patients undergoing spinal fusion surgery, the most suitable tool for the DSD population remains uncertain at present. PATIENTS AND METHODS: The authors reviewed consecutive patients who underwent thoracolumbar fusion surgery for DSD between August 2016 and May 2023. Four screening tools were used to assess preoperative nutritional status. Patients were divided into two categories according to each screening tool, and the four screening tools were compared regarding their predictive power for postoperative AEs, including the rates of extended length of hospital stays (LOS), complications, and readmission within three months. Physical functional indicators such as time to first ambulation, nonhome discharge, and postoperative LOS were assessed as secondary outcome measures. A multivariable logistic regression analysis was used to identify factors associated with postoperative AEs. RESULTS: A total of 228 patients were included. The demographic characteristics, underlying disease, and magnitude of correction were not significantly different between well-nourished and malnourished groups. The nutritional risks shown by MNA-SF and albumin level were significantly associated with infectious complications ( P <0.05). The nutritional risk shown by MNA-SF was significantly associated with nonhome discharge, prolonged postoperative LOS (12.5±8.2 vs. 10.3±6.1, P =0.039), and delayed ambulation (3.7±2.1 vs. 2.2±1.8, P =0.001). Multivariable logistic regression revealed that PNI <50 was significantly associated with total AEs and minor AEs after DSD surgery. CONCLUSIONS: PNI was significantly associated with the incidence of total AEs and minor AEs, while preoperative albumin level and MNA-SF were more effective in predicting postoperative infectious complications and delayed recovery of physical function, respectively. LEVEL OF EVIDENCE: Level III.
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Desnutrición , Estado Nutricional , Humanos , Anciano , Evaluación Nutricional , Estudios Retrospectivos , Desnutrición/diagnóstico , Albúminas , Complicaciones Posoperatorias/epidemiologíaRESUMEN
BACKGROUND: The burden of lumbar degenerative diseases (LDD) has increased substantially with the unprecedented aging population. Identifying elderly patients with high risk of postoperative adverse events (AEs) and establishing individualized perioperative management is critical to mitigate added costs and optimize cost-effectiveness to the healthcare system. We aimed to develop a predictive tool for AEs in elderly patients with transforaminal lumbar interbody fusion (TLIF), utilizing multivariate logistic regression, single classification and regression tree (hereafter, "classification tree"), and random forest machine learning algorithms. METHODS: This study was a retrospective review of a prospective Geriatric Lumbar Disease Database (age ≥ 65). Our outcome measure was postoperative AEs, including prolonged hospital stays, postoperative complications, readmission, and reoperation within 90 days. Patients were grouped as either having at least one adverse event (AEs group) or not (No-AEs group). Three models for predicting postoperative AEs were developed using training dataset and internal validation using testing dataset. Finally, online tool was developed to assess its validity in the clinical setting (external validation). RESULTS: The development set included 1025 patients (mean [SD] age, 72.8 [5.6] years; 632 [61.7%] female), and the external validation set included 175 patients (73.2 [5.9] years; 97 [55.4%] female). The predictive ability of our three models was comparable, with no significant differences in AUC (0.73 vs. 0.72 vs. 0.70, respectively). The logistic regression model had a higher net benefit for clinical intervention than the other models. A nomogram based on logistic regression was developed, and the C-index of external validation for AEs was 0.69 (95% CI 0.65-0.76). CONCLUSION: The predictive ability of our three models was comparable. Logistic regression model had a higher net benefit for clinical intervention than the other models. Our nomogram and online tool ( https://xuanwumodel.shinyapps.io/Model_for_AEs/ ) could inform physicians about elderly patients with a high risk of AEs within the 90 days after TLIF surgery.
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Nomogramas , Fusión Vertebral , Humanos , Anciano , Vértebras Lumbares/cirugía , Estudios Prospectivos , Fusión Vertebral/efectos adversos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios RetrospectivosRESUMEN
BACKGROUND CONTEXT: Elderly patients are less likely to recover from lumbar spine fusion (LSF) as rapidly compared with younger patients. However, there is still a lack of research on the effect of early ambulation on elderly patients undergoing LSF surgery for lumbar degenerative disorders. PURPOSE: To evaluate the safety and benefit of ambulation within 24 hours in elderly patients who underwent LSF. STUDY DESIGN: A retrospective study. PATIENT SAMPLE: Consecutive patients (aged 65 and older) who underwent elective transforaminal lumbar interbody fusion surgery for degenerative disorders from January 2019 to October 2022. OUTCOME MEASURES: Outcome measures included postoperative complications, postoperative drainage (mL), laboratory test data, length of hospital stay [LOS], readmission and reoperation within 3 months. METHODS: Early ambulation patients (ambulation within 24 hours after surgery) were propensity-score matched 1:1 to a delayed ambulation patients (ambulation at a minimum of 48 hours postoperatively) based on age, intraoperative blood loss, and number of fused segments. The incidence of postoperative adverse events (AEs, including rates of complications, readmission, and prolonged LOS) and the average LOS were used to assess the safety and benefit of early ambulation, respectively. Multivariable regression analysis was performed to assess the association between early ambulation and postoperative AEs. The risk factors for delayed ambulation were also determined using multivariable logistic analyses. RESULTS: A total of 998 patients with LSF surgery were reviewed in this study. After excluding 116 patients for various reasons, 882 patients (<24 hours: N=350, 24-48 hours: N=230, and >48 hours: N= 302) were included in the final analysis. After matching, sex, BMI, preoperative comorbidities, laboratory test data and surgery-related variables were comparable between the groups. The incidence of postoperative AEs was significantly lower in the EA group (44.3% vs. 64.0%, p<.001). The average postoperative LOS of the EA group was 2 days shorter than the DA group (6.5 days vs. 8.5 days, p<.001). Patients in the EA group had a significantly lower rate of prolonged LOS compared with the DA group (35.1% vs. 55.3%, p<.001). There was no significant difference in postoperative drainage volumes between the two groups. Multivariable analysis identified older age (odds ratio [OR] 1.07, p<.001), increased intraoperative EBL (OR 1.002, p=.001), and higher international normalization ratio (OR 10.57, p=.032) as significant independent risk factors for delayed ambulation. CONCLUSIONS: Ambulation within 24 hours after LSF surgery is independently associated fewer AEs and shorter hospital stays in elderly patients. Implementing the goal of ambulation within 24 hours after LSF surgery into enhanced recovery after surgery protocols for elderly patients seems appropriate. Older age, increased intraoperative blood loss and worse coagulation function are associated with delayed ambulation.
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To investigate the effects of leaves and stems on the accumulation and transport of cadmium(Cd) and arsenic(As) in wheat shoots after flowering, a field experiment was conducted in a typical Cd and As co-contaminated agricultural land to explore the distribution and translocation of Cd and As in the different parts of two wheat cultivars after flowering. The results showed that Cd was mainly distributed in the nodes of two varieties, and the translocation factors of Cd from internode 3 to node 2, from internode 2 to node 1, and from sheath 1 to node 1 were markedly higher than those of other aboveground parts during the grain-filling stage. However, Cd was mainly distributed in the leaves, and the translocation factors of Cd from sheath to leaf and from node 1 to rachis was significantly higher than those of other parts at the mature stage. In addition, the transport capacity of Cd from glume to rachis and from rachis to grain in JM22 was significantly lower than that in SN28, which significantly reduced Cd concentrations in the rachis, glume, and grain of JM22 by 22.3%, 40.8%, and 44.4%, respectively. Meanwhile, As was mainly distributed in the wheat leaves from the grain-filling stage to the mature stage, and As concentrations in the glume and grain of JM22 were 25.8% and 33.3% lower than those of SN28, respectively. Additionally, the translocation factors of As from the sheath to the node were significantly 438% and 190% higher than that from leaf to sheath and from node to internode during the whole grain filling stage and mature stage. Moreover, the translocation factors of As from glumes to grains and from rachis to grains in JM22 were 40.6% and 44.4% lower than that in SN28, respectively. In summary, flag leaf, node 1, and the rachis had regulated Cd transport and accumulation in wheat grains, whereas leaf 3, flag leaf, node 1, the glumes, and the rachis were mainly responsible for As transport and accumulation in wheat grains.
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Arsénico , Contaminantes del Suelo , Cadmio/análisis , Triticum , Grano Comestible/química , Agricultura , Contaminantes del Suelo/análisis , SueloRESUMEN
Background: Disc height (DH) change is considered one of the most critical factors in assessing intervertebral disc degeneration (IVD). Pfirrmann et al. developed a scoring system for disc degeneration evaluation based on changes in DH in magnetic resonance imaging (MRI). While the relationship between DH measurements and Pfirrmann scores for disc degeneration has been explored, the validity of different DH measuring techniques or their connection with disc degeneration is yet uncertain. The present study investigates intra-rater and inter-rater agreement and reliability of different DH measurement methods on MRI and evaluates the relationship between different DH measurement methods and Pfirrmann scores of IVD degeneration, as well as between different Pfirrmann scores and clinical outcomes. Methods: Adult patients with MRI scans of the lumbar spine were recruited. Eight DH measuring techniques were tested for intra-rater and inter-rater agreement and reliability. Bland and Altman's Limits of Agreement (LOA) was used to evaluate intra-rater and inter-rater agreements. Intra-rater and inter-rater reliability were evaluated using intra-class correlations (ICC) with 95 % confidence intervals (95 % CI). The association between DH and Pfirrmann scores was examined using one-way ANOVA. Results: Excellent intra-rater reliability was reported for 332 participants on DH (ranging from 0.912 (0.901, 0.923) to 0.973 (0.964, 0.981) and from 0.902 (0.892, 0.915) to 0.975 (0.962, 0.985) by two independent raters). All measuring methods had high intra-rater agreement, except for methods 4 and 5. All methods had good-to-excellent of inter-rater reliability on DH (ICCs ranging from 0.812 (0.795, 0.828) to 0.995 (0.994, 0.995)) except for the posterior disc material length of method 5 (ICC 0.740 (0.718, 0.761)). Methods 1 to 6 for evaluating DH in patients with spondylolisthesis had poor inter-rater reliability. The IVD levels with grades IV and V in Pfirrmann scores had significantly lower DH than the IVD levels with grades I to III in Pfirrmann scores. IVD levels with grades IV and V in Pfirrmann scores had significantly higher VAS and ODI than IVD levels with grades I in Pfirrmann scores. Conclusion: A good-to-excellent intra-rater and inter-rater reliability was achieved on most DH measuring methods on MRI following a standardized and structured protocol. However, small anatomical structures and different tissue borders could influence measurements. Additionally, DH can differentiate between grade IV and V Pfirrmann scores, and severe IVD degeneration (IV and V Pfirrmann) is linked to clinical outcomes.
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Kidney disease can be caused by various internal and external factors that have led to a continual increase in global deaths. Current treatment methods can alleviate but do not markedly prevent disease development. Further research on kidney disease has revealed the crucial function of epigenetics, especially acetylation, in the pathology and physiology of the kidney. Histone acetyltransferases (HATs), histone deacetylases (HDACs), and acetyllysine readers jointly regulate acetylation, thus affecting kidney physiological homoeostasis. Recent studies have shown that acetylation improves mechanisms and pathways involved in various types of nephropathy. The discovery and application of novel inhibitors and activators have further confirmed the important role of acetylation. In this review, we provide insights into the physiological process of acetylation and summarise its specific mechanisms and potential therapeutic effects on renal pathology.
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Enfermedades Renales , Humanos , Acetilación , Enfermedades Renales/tratamiento farmacológico , Riñón , Epigénesis Genética , EpigenómicaRESUMEN
AIM: Ibuprofen is the most commonly used analgesic. CYP polymorphisms are mainly responsible for the differences in drug metabolism among individuals. Variations in the ability of populations to metabolize ibuprofen can lead to drug exposure events. The aim of this study was to evaluate the effects of CYP2C19 and CYP3A4 polymorphisms on ibuprofen metabolism in a Chinese population. METHODS: First, 31 CYP2C19 and 12 CYP3A4 microsomal enzymes were identified using an insect expression system. Then, variants were evaluated using a mature incubation system. Moreover, ibuprofen metabolite content was determined via ultra-performance liquid chromatography-tandem mass spectrometry analysis. Finally, kinetic parameters of CYP2C19 and CYP3A4 genotypes were determined via Michaelis-Menten curve fitting. RESULTS: Most variants exhibited significantly altered intrinsic clearance compared to the wild type. In the CYP2C19 metabolic pathway, seven variants exhibited no significant alterations in intrinsic clearance (CLint), six variants exhibited significantly high CLint (121-291%), and the remaining 15 variants exhibited substantially reduced CLint (1-71%). In the CYP3A4 metabolic pathway, CYP3A4*30 was not detected in the metabolite content due to the absence of activity, and 10 variants exhibited significantly reduced CLint. CONCLUSION: To the best of our knowledge, this is the first study to assess the kinetic characteristics of 31 CYP2C19 and 12 CYP3A4 genotypes on ibuprofen metabolism. However, further studies are needed on poor metabolizers as they are more susceptible to drug exposure. Our findings suggest that the kinetic characteristics in combination with artificial intelligence to predict the toxicity of ibuprofen and reduce any adverse drug reactions.
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Citocromo P-450 CYP3A , Ibuprofeno , Humanos , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Citocromo P-450 CYP2C19/genética , Inteligencia Artificial , Polimorfismo GenéticoRESUMEN
Signal transducer and activator of transcription 3 (STAT3) is a cell-signal transcription factor that has attracted considerable attention in recent years. The stimulation of cytokines and growth factors can result in the transcription of a wide range of genes that are crucial for several cellular biological processes involved in pro- and anti-inflammatory responses. STAT3 has attracted considerable interest as a result of a recent upsurge in study because of their role in directing the innate immune response and sustaining inflammatory pathways, which is a key feature in the pathogenesis of many diseases, including renal disorders. Several pathological conditions which may involve STAT3 include diabetic nephropathy, acute kidney injury, lupus nephritis, polycystic kidney disease, and renal cell carcinoma. STAT3 is expressed in various renal tissues under these pathological conditions. To better understand the role of STAT3 in the kidney and provide a theoretical foundation for STAT3-targeted therapy for renal disorders, this review covers the current work on the activities of STAT3 and its mechanisms in the pathophysiological processes of various types of renal diseases.