Search

BackgroundThe current treatment strategy for metastatic Hormone-Sensitive Prostate Cancer (mHSPC) is the combination of Androgen Receptor Signaling Inhibitors (ARSIs) medicines with androgen deprivation therapy (ADT). However, there is a lack of real-world data comparing the efficacy of different ARSI pharmaceuticals. Therefore, the objective of this study was to compare the effectiveness and safety of bicalutamide, abiraterone, enzalutamide, and apalutamide in combination with ADT for patients with mHSPC.MethodsWe retrospectively analyzed 82 patients diagnosed with mHSPC, including 18 patients treated with abiraterone acetate with prednisone, 21 patients with enzalutamide, 20 patients with apalutamide, and 23 patients with bicalutamide. We evaluated PSA progression-free survival (PSA-PFS), imaging progression-free survival (r PFS), castration resistance progression-free survival (CRPC-PFS), and overall survival (OS) using Kaplan-Meier survival analyses. Additionally, we explored relevant factors affecting prognosis through univariate and multivariate Cox risk-proportionality models. PSA response rates at 3, 6, and 12 months, nadir PSA levels (nPSA), and time to nadir (TTN) in different medication subgroups after treatment were documented, and we used one-way ANOVA to determine the effect of these measures on patient prognosis.ResultsIn comparison with bicalutamide, both enzalutamide and apalutamide have shown significant advantages in delaying disease progression among mHSPC patients. Specifically, enzalutamide has been found to significantly prolong PSA-PFS (HR 2.244; 95% CI 1.366-3.685, p=0.001), rPFS (HR 2.539; 95% CI 1.181-5.461; p= 0.007), CRPC-PFS (HR 2.131; 95% CI 1.295-3.506; p= 0.003), and OS (HR 2.06; 95% CI 1.183-3.585; P=0.005). Similarly, apalutamide has significantly extended PSA-PFS (HR 5.071; 95% CI 1.711-15.032; P= 0.003) and CRPC-PFS (HR 6.724; 95% CI 1.976-22.878; P=0.002) among patients. On the other hand, the use of abiraterone in combination with ADT did not demonstrate a significant advantage in delaying diseases progression when compared with the other three agents in mHSPC patients. There were no significant differences in overall adverse event rates among the four pharmaceuticals in terms of safety. Additionally, the observation of PSA kinetics revealed that enzalutamide, apalutamide, and abiraterone acetate had a significant advantage in achieving deep PSA response (PSA ≤ 0.2 ng/ml) compared with bicalutamide (p=0.007 at 12 months). Enzalutamide and apalutamide exhibited preeminence efficacy, with no substantial difference observed between the two medications.ConclusionsAbiraterone, enzalutamide, and apalutamide were found to significantly reduce and stabilize PSA levels in mHSPC patients more quickly and thoroughly than bicalutamide. Furthermore, enzalutamide and apalutamide were found to significantly prolong survival and delay disease progression in mHSPC patients compared with bicalutamide. It should be noted that abiraterone did not demonstrate a significant advantage in delaying disease compared with enzalutamide and apalutamide. After conducting drug toxicity analyses, it was determined that there were no significant differences among the four drugs.

Abstract Neurotoxicity of organophosphate compounds (OPs) can catastrophically cause nervous system injury by inhibiting acetylcholinesterase (AChE) expression. Although artificial systems have been developed for indirect neuroprotection, they are limited to dissociating P-O bonds for eliminating OPs. However, these systems have failed to overcome the deactivation of AChE. Herein, we report our finding that Al3+ is engineered onto the nodes of metal–organic framework to synthesize MOF-808-Al with enhanced Lewis acidity. The resultant MOF-808-Al efficiently mimics the catalytic behavior of AChE and has a self-defense ability to break the activity inhibition by OPs. Mechanism investigations elucidate that Al3+ Lewis acid sites with a strong polarization effect unite the highly electronegative –OH groups to form the enzyme-like catalytic center, resulting in superior substrate activation and nucleophilic attack ability with a 2.7-fold activity improvement. The multifunctional MOF-808-Al, which has satisfactory biosafety, is efficient in reducing neurotoxic effects and preventing neuronal tissue damage.

Abstract Background At present, there are two techniques which are widely applied clinically; the midline and the paramedian. Both methods are difficult for clinicians when treating the elderly. The aim of this work is to explore the feasibility of an ultrasound-assisted modified paramedian technique for spinal anesthesia in the elderly. This would provide clinicians with a new and easy-to-operate technique. Methods A total of 150 elderly patients who were scheduled for urology surgery under spinal anesthesia in our hospital were randomly divided into three groups (n = 50): (i) midline technique group (group M), (ii) paramedian technique group (group P), and (iii) modified paramedian technique group (group PM). All spinal anesthesia were performed by the same second-year resident. Results Compared with groups M and P, group PM had significantly higher first-attempt success rate (P

Forest canopy height is a basic metric characterizing forest growth and carbon sink capacity. Based on full-polarized Advanced Land Observing Satellite/Phased Array type L-band Synthetic Aperture Radar (ALOS/PALSAR) data, this study used Polarimetric Interferometric Synthetic Aperture Radar (PolInSAR) technology to estimate forest canopy height. In total the four methods of differential DEM (digital elevation model) algorithm, coherent amplitude algorithm, coherent phase-amplitude algorithm and three-stage random volume over ground algorithm (RVoG_3) were proposed to obtain canopy height and their accuracy was compared in consideration of the impacts of coherence coefficient and range slope levels. The influence of the statistical window size on the coherence coefficient was analyzed to improve the estimation accuracy. On the basis of traditional algorithms, time decoherence was performed on ALOS/PALSAR data by introducing the change rate of Landsat NDVI (Normalized Difference Vegetation Index). The slope in range direction was calculated based on SRTM (Shuttle Radar Topography Mission) DEM data and then introduced into the s-RVoG (sloped-Random Volume over Ground) model to optimize the canopy height estimation model and improve the accuracy. The results indicated that the differential DEM algorithm underestimated the canopy height significantly, while the coherent amplitude algorithm overestimated the canopy height. After removing the systematic coherence, the overestimation of the RVoG_3 model was restrained, and the absolute error decreased from 23.68 m to 4.86 m. With further time decoherence, the determination coefficient increased to 0.2439. With the introduction of range slope, the s-RVoG model shows improvement compared to the RVoG model. Our results will provide a reference for the appropriate algorithm selection and optimization for forest canopy height estimation using full-polarized L-band synthetic aperture radar (SAR) data for forest ecosystem monitoring and management.