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Venous thromboembolism (VTE) poses a notable risk of morbidity and mortality. The natural resolution of the venous thrombus might be a potential alternative treatment strategy for VTE. Monocytes/macrophages merge as pivotal cell types in the gradual resolution of the thrombus. In this review, the vital role of macrophages in inducing inflammatory response, augmenting neovascularization, and facilitating the degradation of fibrin and collagen during thrombus resolution was described. The two phenotypes of macrophages involved in thrombus resolution and their dual functions were discussed. Macrophages expressing various factors, including cytokines and their receptors, adhesion molecules, chemokine receptors, vascular endothelial growth factor receptors, profibrinolytic- or antifibrinolytic-related enzymes, and other elements, are explored for their potential to promote or attenuate thrombus resolution. Furthermore, this review provides a comprehensive summary of new and promising therapeutic candidate drugs associated with monocytes/macrophages that have been demonstrated to promote or impair thrombus resolution. However, further clinical trials are essential to validate their efficacy in VTE therapy.
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Macrófagos , Monocitos , Trombosis de la Vena , Humanos , Monocitos/inmunología , Monocitos/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Animales , Trombosis de la Vena/inmunología , Trombosis de la Vena/metabolismo , Tromboembolia Venosa/inmunología , Tromboembolia Venosa/patología , Tromboembolia Venosa/tratamiento farmacológicoRESUMEN
Cryptococcus neoformans is at the top of the list of "most wanted" human pathogens. Only three classes of antifungal drugs are available for the treatment of cryptococcosis. Studies on antifungal resistance mechanisms are limited to the investigation of how a particular antifungal drug induces resistance to a particular drug, and the impact of stresses other than antifungals on the development of antifungal resistance and even cross-resistance is largely unexplored. The endoplasmic reticulum (ER) is a ubiquitous subcellular organelle of eukaryotic cells. Brefeldin A (BFA) is a widely used chemical inducer of ER stress. Here, we found that both weak and strong selection by BFA caused aneuploidy formation in C. neoformans, mainly disomy of chromosome 1, chromosome 3, and chromosome 7. Disomy of chromosome 1 conferred cross-resistance to two classes of antifungal drugs: fluconazole and 5-flucytosine, as well as hypersensitivity to amphotericin B. However, drug resistance was unstable, due to the intrinsic instability of aneuploidy. We found overexpression of AFR1 on Chr1 and GEA2 on Chr3 phenocopied BFA resistance conferred by chromosome disomy. Overexpression of AFR1 also caused resistance to fluconazole and hypersensitivity to amphotericin B. Furthermore, a strain with a deletion of AFR1 failed to form chromosome 1 disomy upon BFA treatment. Transcriptome analysis indicated that chromosome 1 disomy simultaneously upregulated AFR1, ERG11, and other efflux and ERG genes. Thus, we posit that BFA has the potential to drive the rapid development of drug resistance and even cross-resistance in C. neoformans, with genome plasticity as the accomplice.
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Aneuploidia , Antifúngicos , Brefeldino A , Cryptococcus neoformans , Farmacorresistencia Fúngica , Cryptococcus neoformans/efectos de los fármacos , Cryptococcus neoformans/genética , Brefeldino A/farmacología , Antifúngicos/farmacología , Farmacorresistencia Fúngica/genética , Fluconazol/farmacología , Anfotericina B/farmacología , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Pruebas de Sensibilidad Microbiana , Flucitosina/farmacología , Humanos , Estrés del Retículo Endoplásmico/efectos de los fármacosRESUMEN
OBJECTIVE: Secretoneurin may play a brain-protective role. We aim to discover the relationship between serum secretoneurin levels and severity plus neurological outcome after intracerebral hemorrhage (ICH). METHODS: In this prospective cohort study, serum secretoneurin levels were measured in 110 ICH patients and 110 healthy controls. Glasgow Coma Scale (GCS) and hematoma volume were used to assess stroke severity. Poor prognosis was defined as Glasgow Outcome Scale (GOS) scores of 1-3 at 90 days after ICH. A multivariate logistic regression model was constructed to determine independent correlation of serum secretoneurin levels with severity and poor prognosis. Under receiver operating characteristic (ROC) curve, prognostic ability of serum secretoneurin levels was assessed. Restricted cubic spline (RCS) model and subgroups analysis were used for discovering association of serum secretoneurin levels with risk of poor prognosis. Calibration curve and decision curve were evaluated to confirm performance of nomogram. RESULTS: Serum secretoneurin levels of patients were significantly higher than those of healthy controls. Serum secretoneurin levels of patients were independently correlated with GCS scores and hematoma volume. There were 42 patients with poor prognosis at 90 days following ICH. Serum secretoneurin levels were significantly higher in patients with poor outcome than in those with good outcome. Under the ROC curve, serum secretoneurin levels significantly differentiated poor outcome. Serum secretoneurin levels ≥ 22.8 ng/mL distinguished patients at risk of poor prognosis at 90 days with a sensitivity of 66.2% and a specificity of 81.0%. Besides, serum secretoneurin levels independently predicted a 90-day poor prognosis. Subgroup analysis showed that serum secretoneurin levels had non-significant interactions with other variables. The nomogram, including independent prognostic predictors, showed reliable prognosis capability using calibration curve and decision curve. Area under the curve of the predictive model was significantly higher than those of GCS scores and hematoma volume. CONCLUSION: Serum secretoneurin levels are strongly related to ICH severity and poor prognosis at 90 days after ICH. Thus, serum secretoneurin may be a promising prognostic biomarker in ICH.
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Biomarcadores , Hemorragia Cerebral , Humanos , Masculino , Hemorragia Cerebral/sangre , Hemorragia Cerebral/diagnóstico , Femenino , Persona de Mediana Edad , Pronóstico , Anciano , Biomarcadores/sangre , Estudios Prospectivos , Neuropéptidos/sangre , Secretogranina II/sangre , Escala de Coma de Glasgow , Estudios de Cohortes , Adulto , Curva ROC , Escala de Consecuencias de GlasgowRESUMEN
Alcoholic fatty liver disease (FALD) and non-alcoholic fatty liver disease (NAFLD) have similar pathological spectra, both of which are associated with a series of symptoms, including steatosis, inflammation, and fibrosis. These clinical manifestations are caused by hepatic lipid synthesis and metabolism dysregulation and affect human health. Despite having been studied extensively, targeted therapies remain elusive. The Cytochrome P450 (CYP450) family is the most important drug-metabolising enzyme in the body, primarily in the liver. It is responsible for the metabolism of endogenous and exogenous compounds, completing biological transformation. This process is relevant to the occurrence and development of AFLD and NAFLD. In this review, the correlation between CYP450 and liver lipid metabolic diseases is summarised, providing new insights for the treatment of AFLD and NAFLD.
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Food security is closely related to the development of human society, and the root of food production lies in cultivated land, with water conservancy as its lifeline. This study estimates the ecological water consumption of located in the arid region of Northwest China (the Karamay region and Muzat River basin) from 1990 to 2020 based on the optimized Land Surface Energy Balance Algorithm. The verification accuracy of SEBAL energy balance model is greatly improved after optimization. It was showed an increasing trend in the Karamay region and Muzat River basin, increasing at the rates of 2.84 mm/year and 2.86 mm/year respectively. The suitability of cultivated land was evaluated by combining four periods of 30 m spatial resolution land use/land cover data from 1990, 2000, 2010, and 2020, as well as the Hydrological Statistical Yearbook and Xinjiang Statistical Yearbook. Through the analysis of spatial optimization for cultivated land, it can be inferred that the primary limiting factors affecting cultivated land suitability in the Karamay region are irrigation guarantee rate (54.03%) and soil salinity (11.98%). Muzat River region are irrigation guarantee rate (32.19%) and soil salinity (18.62%). By comparing the scenarios of setting ecological priority and cultivated land priority, it is concluded that under the conditions of water resource constraints and 50%, 75% and 90% design irrigation assurance rates, Karamay still has cultivated land expansion potential, which can be used as the main preparatory reclamation area. In addition to the traditional agriculture irrigation area, the Muzat River basin still has development potential under the condition of ecological priority and no more than 75% irrigation design assurance rate. The study on the cultivated land suitability under the condition of water resource constraints can provide new ideas for food security.
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As an excellent single-stage object detector based on neural networks, YOLOv5 has found extensive applications in the industrial domain; however, it still exhibits certain design limitations. To address these issues, this paper proposes Efficient Scale Fusion YOLO (ESF-YOLO). Firstly, the Multi-Sampling Conv Module (MSCM) is designed, which enhances the backbone network's learning capability for low-level features through multi-scale receptive fields and cross-scale feature fusion. Secondly, to tackle occlusion issues, a new Block-wise Channel Attention Module (BCAM) is designed, assigning greater weights to channels corresponding to critical information. Next, a lightweight Decoupled Head (LD-Head) is devised. Additionally, the loss function is redesigned to address asynchrony between labels and confidences, alleviating the imbalance between positive and negative samples during the neural network training. Finally, an adaptive scale factor for Intersection over Union (IoU) calculation is innovatively proposed, adjusting bounding box sizes adaptively to accommodate targets of different sizes in the dataset. Experimental results on the SODA10M and CBIA8K datasets demonstrate that ESF-YOLO increases Average Precision at 0.50 IoU (AP50) by 3.93 and 2.24%, Average Precision at 0.75 IoU (AP75) by 4.77 and 4.85%, and mean Average Precision (mAP) by 4 and 5.39%, respectively, validating the model's broad applicability.
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Background. Pancreatic cancer is one of the most malignant tumours, demonstrating a poor prognosis and nearly identically high mortality and morbidity, mainly because of the difficulty of early diagnosis and timely treatment for localized stages.Objective. To develop a noncontrast CT (NCCT)-based pancreatic lesion detection model that could serve as an intelligent tool for diagnosing pancreatic cancer early, overcoming the challenges associated with low contrast intensities and complex anatomical structures present in NCCT images.Approach.We design a multiscale and multiperception (MSMP) feature learning network with ResNet50 coupled with a feature pyramid network as the backbone for strengthening feature expressions. We added multiscale atrous convolutions to expand different receptive fields, contextual attention to perceive contextual information, and channel and spatial attention to focus on important channels and spatial regions, respectively. The MSMP network then acts as a feature extractor for proposing an NCCT-based pancreatic lesion detection model with image patches covering the pancreas as its input; Faster R-CNN is employed as the detection method for accurately detecting pancreatic lesions.Main results. By using the new MSMP network as a feature extractor, our model outperforms the conventional object detection algorithms in terms of the recall (75.40% and 90.95%), precision (40.84% and 68.21%), F1 score (52.98% and 77.96%), F2 score (64.48% and 85.26%) and Ap50 metrics (53.53% and 70.14%) at the image and patient levels, respectively.Significance.The good performance of our new model implies that MSMP can mine NCCT imaging features for detecting pancreatic lesions from complex backgrounds well. The proposed detection model is expected to be further developed as an intelligent method for the early detection of pancreatic cancer.
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Neoplasias Pancreáticas , Tomografía Computarizada por Rayos X , Humanos , Neoplasias Pancreáticas/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos , Aprendizaje AutomáticoRESUMEN
Lithium-sulfur (Li-S) batteries are one of the most promising high-energy density secondary batteries due to their high theoretical energy density of 2600 Wh kg-1. However, the sluggish kinetics and severe "shuttle effect" of polysulfides are the well-known barriers that hinder their practical applications. A carefully designed catalytic host of sulfur may be an effective strategy that not only accelerates the conversion of polysulfides but also limit their dissolution to mitigate the "shuttle effect." Herein, in situ surface-phosphided Ni0.96Co0.03Mn0.01O (p-NCMO) oxide microspheres are prepared via gas-phase phosphidation as a catalytic host of sulfur. The as-prepared unique heterostructured microspheres, with enriched surface-coated metal phosphide, exhibit superior synergistic effect of catalytic conversion and absorption of the otherwise soluble intermediate polysulfides. Correspondingly, the sulfur cathode exhibits excellent electrochemical performance, including a high initial discharge capacity (1162 mAh gs-1 at 0.1C), long cycling stability (491 mAh gs-1 after 1000 cycles at 1C), and excellent rate performance (565 mAh gs-1 at 5C). Importantly, the newly prepared sulfur cathode shows a high areal capacity of 4.0 mAh cm-2 and long cycle stability under harsh conditions (high sulfur loading of 5.3 mg cm-2 and lean electrolyte/sulfur ratio of 5.8 µL mg-1). This work proposes an effective strategy to develop the catalytic hosts of sulfur for achieving high-performance Li-S batteries via surface phosphidation.
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BACKGROUND: As the impact of the COVID-19 pandemic winds down, both individuals and society are gradually returning to life and activities before the pandemic. This study aims to explore how people's emotions have changed from the pre-pandemic period during the pandemic to this post-emergency period and whether the sentiment level nowadays has returned to the pre-pandemic level. METHOD: We collected Reddit social media data in 2019 (pre-pandemic), 2020 (peak period of the pandemic), 2021, and 2022 (late stages of the pandemic, transitioning period to the post-emergency period) from the subreddits communities in 128 universities/colleges in the U.S., and a set of school-level baseline characteristics such as location, enrollment, graduation rate, selectivity, etc. We predicted two sets of sentiments from a pre-trained Robustly Optimized BERT pre-training approach (RoBERTa) and a graph attention network (GAT) that leverages both the rich semantic information and the relational information among posted messages and then applied model stacking to obtain the final sentiment classification. After obtaining the sentiment label for each message, we employed a generalized linear mixed-effects model to estimate the temporal trend in sentiment from 2019 to 2022 and how the school-level factors may affect the sentiment. RESULTS: Compared to the year 2019, the odds of negative sentiment in years 2020, 2021, and 2022 are 25%. 7.3%, and 6.3% higher, respectively, which are all statistically significant at the 5% significance level based on the multiplicity-adjusted p-values. CONCLUSIONS: Our study findings suggest a partial recovery in the sentiment composition (negative vs. non-negative) in the post-pandemic-emergency era. The results align with common expectations and provide a detailed quantification of how sentiments have evolved from 2019 to 2022 in the sub-population represented by the sample examined in this study.
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Pandemias , Medios de Comunicación Sociales , Humanos , Universidades , Análisis de Sentimientos , Instituciones Académicas , ActitudRESUMEN
Recent studies have revealed that endophytes in plants can produce metabolites with activity that is comparable to or identical to the host. Dendrobine has attracted much attention in the field of neurodegenerative diseases by exhibiting anti-oxidative stress and neuroprotective effects. This study aimed to investigate the protective effects and mechanisms of metabolites of dendrobium endophytes Pseudomonas protegens CM-YJ44 and Priestia megaterium D-HT207 against H2O2-induced oxidative stress injury in SH-SY5Y cells. Results showed that there were 50 neuroprotective compounds in CM-YJ44 and 72 neuroprotective compounds in D-HT207. Those both increased significantly cell viability, decreased contents of ROS in H2O2-induced SH-SY5Y cells. It was confirmed that metabolites of CM-YJ44 and D-HT207 inhibited the H2O2-induced oxidative stress injury in SH-SY5Y cells, which mechanism is related to inhibition of ROS production, alteration of MMP, and inhibition of apoptosis and inflammatory factors expression via the Nrf2/Keap1 pathway.
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Aiming at the rapid development of anti-hypersonic collaborative interception technology, this paper designs an intelligent maneuver strategy of hypersonic vehicles (HV) based on deep reinforcement learning (DRL) to evade the collaborative interception by two interceptors. Under the meticulously designed collaborative interception strategy, the uncertainty and difficulty of evasion are significantly increased and the opportunity for maneuvers is further compressed. This paper, accordingly, selects the twin delayed deep deterministic gradient (TD3) strategy acting on the continuous action space and makes targeted improvements combining deep neural networks to grasp the maneuver strategy and achieve successful evasion. Focusing on the time-coordinated interception strategy of two interceptors, the three-player pursuit and evasion (PE) problem is modeled as the Markov decision process, and the double training strategy is proposed to juggle both interceptors. In reward functions of the training process, the energy saving factor is set to achieve the trade-off between miss distance and energy consumption. In addition, the regression neural network is introduced into the deep neural network of TD3 to enhance intelligent maneuver strategies' generalization. Finally, numerical simulations are conducted to verify that the improved TD3 algorithm can effectively evade the collaborative interception of two interceptors under tough situations, and the improvements of the algorithm in terms of convergence speed, generalization, and energy-saving effect are verified.
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Silicosis is a systemic disease caused by long-term inhalation of free SiO2 and retention in the lungs. At present, it is still the most important occupational health hazard disease in the world. Existing studies have shown that non-coding RNA can also participate in complex fibrosis regulatory networks. However, its role in regulating silicotic fibrosis is still unclear. In this study, we constructed a NR8383/RLE-6TN co-culture system to simulate the pathogenesis of silicosis in vitro. Design of miR-204-3p mimics and inhibitors to overexpress or downregulate miR-204-3p in RLE-6TN cells. Design of short hairpin RNA (sh-RNA) to downregulate MRAK052509 in RLE-6TN cells. The regulatory mechanism of miR-204-3p and LncRNA MRAK052509 on EMT process was studied by Quantitative real-time PCR, Western blotting, Immunofluorescence and Cell scratch test. The results revealed that miR-204-3p affects the occurrence of silica dust-induced cellular EMT process mainly through regulating TGF-ßRΙ, a key molecule of TGF-ß signaling pathway. In contrast, Lnc MRAK052509 promotes the EMT process in epithelial cells by competitively adsorbing miR-204-3p and reducing its inhibitory effect on the target gene TGF-ßRΙ, which may influence the development of silicosis fibrosis. This study perfects the targeted regulation relationship between LncRNA MRAK052509, miR-204-3p and TGF-ßRΙ, and may provide a new strategy for the study of the pathogenesis and treatment of silicosis.
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Transición Epitelial-Mesenquimal , MicroARNs , ARN Largo no Codificante , Dióxido de Silicio , Silicosis , Animales , Humanos , Ratas , Línea Celular , Polvo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Transición Epitelial-Mesenquimal/efectos de los fármacos , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , Dióxido de Silicio/toxicidad , Silicosis/genética , Silicosis/patologíaRESUMEN
BACKGROUND: Breast cancer is the most prevalent malignant tumor among women, with hormone receptor-positive cases constituting 70%. Fulvestrant, an antagonist for these receptors, is utilized for advanced metastatic hormone receptor-positive breast cancer. Yet, its inhibitory effect on tumor cells is not strong, and it lacks direct cytotoxicity. Consequently, there's a significant challenge in preventing recurrence and metastasis once cancer cells develop resistance to fulvestrant. METHOD: To address these challenges, we engineered tumor-targeting nanoparticles termed 131I-fulvestrant-ALA-PFP-FA-NPs. This involved labeling fulvestrant with 131I to create 131I-fulvestrant. Subsequently, we incorporated the 131I-fulvestrant and 5-aminolevulinic acid (ALA) into fluorocarbon nanoparticles with folate as the targeting agent. This design facilitates a tri-modal therapeutic approach-endocrine therapy, radiotherapy, and PDT for estrogen receptor-positive breast cancer. RESULTS: Our in vivo and in vitro tests showed that the drug-laden nanoparticles effectively zeroed in on tumors. This targeting efficiency was corroborated using SPECT-CT imaging, confocal microscopy, and small animal fluorescence imaging. The 131I-fulvestrant-ALA-PFP-FA-NPs maintained stability and showcased potent antitumor capabilities due to the synergism of endocrine therapy, radiotherapy, and CR-PDT. Throughout the treatment duration, we detected no notable irregularities in hematological, biochemical, or histological evaluations. CONCLUSION: We've pioneered a nanoparticle system loaded with radioactive isotope 131I, endocrine therapeutic agents, and a photosensitizer precursor. This system offers a combined modality of radiotherapy, endocrine treatment, and PDT for breast cancer.
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Neoplasias de la Mama , Animales , Humanos , Femenino , Fulvestrant/farmacología , Fulvestrant/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Interacciones Farmacológicas , Radioisótopos de YodoRESUMEN
Phenylketonuria (PKU) is an autosomal genetic disorder caused by a deficiency of the phenylalanine hydroxylase (PAH) enzyme. The lack of PAH results in the inability of phenylalanine (PHE) to transform into tyrosine (TYR). Consequently, this leads to the accumulation of PHE in the blood samples of newborns causing metabolic diseases such as irreversible neurological problems. An analysis was required for determining the values of PHE and TYR in blood samples from newborn babies. In this study, therefore, we developed a derivatized method to monitor PHE and TYR in plasma samples using liquid phase chromatography linked with quadrupole mass spectrometry. Accessible formaldehyde isotopes and cyanoborohydride were used to react with PHE and TYR amino groups to generate h2-formaldehyde-modified PHE and TYR (as standards) and d2-formaldehyde-modified PHE and TYR (as internal standards). We used tandem mass spectrometry for multiple reaction monitoring. We demonstrated a derivatized method suitable for the PKU screening of newborns. The recoveries for PHE and TYR were 85% and 90%, respectively. Furthermore, we compared the values of PHE and TYR in different human plasma sample storage methods, including direct plasma and dried blood spots, and the results showed no significant difference.
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Fenilalanina Hidroxilasa , Fenilcetonurias , Recién Nacido , Humanos , Tamizaje Neonatal/métodos , Tirosina , Fenilalanina , Fenilcetonurias/diagnóstico , Espectrometría de Masas en Tándem/métodos , Cromatografía Liquida , Análisis Espectral , FormaldehídoRESUMEN
Electrochemical CO2 reduction reaction (CO2RR) in acid can solve alkalinity issues while highly corrosive and reductive acidic electrolytes usually cause catalyst degradation. Inhibiting catalyst degradation is crucial for the stability of acidic CO2RR. Here, we reveal the microenvironment changes of dynamic Bi-based catalysts and develop a pulse chronoamperometry (CA) strategy to improve the stability of acidic CO2RR. In situ fluorescence mappings show that the local pH changes from neutral to acid, and the in situ Raman spectra reveal the dynamic evolution of interfacial water structures in the microenvironment. We propose that the surface charge properties of dynamic catalysts affect the competitive adsorption of K+ and protons, thereby causing the differences in local pH and CO2RR intermediate adsorption. We also develop a pulse CA strategy to reactivate catalysts, and the stability of acidic CO2RR is improved by 2 orders of magnitude for 100 h operation, which is higher than most reports on the stability of acidic CO2RR. This work gives insights on how microenvironment changes affecting the stability of acidic CO2RR, and provides guidance for designing stable catalysts in acidic electrolytes.
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3D metal-organic frameworks (MOFs) have gained attention as heterogeneous photocatalysts due to their porosity and unique host-guest interactions. Despite their potential, MOFs face challenges, such as inefficient mass transport and limited light penetration in photoinduced energy transfer processes. Recent advancements in organic photocatalysis have uncovered a variety of photoactive cores, while their heterogenization remains an underexplored area with great potential to build MOFs. This gap is bridged by incorporating photoactive cores into 2D MOF nanosheets, a process that merges the realms of small-molecule photochemistry and MOF chemistry. This approach results in recyclable heterogeneous photocatalysts that exhibit an improved mass transfer efficiency. This research demonstrates a bottom-up synthetic method for embedding photoactive cores into 2D MOF nanosheets, successfully producing variants such as PCN-641-NS, PCN-643-NS, and PCN-644-NS. The synthetic conditions were systematically studied to optimize the crystallinity and morphology of these 2D MOF nanosheets. Enhanced host-guest interactions in these 2D structures were confirmed through various techniques, particularly solid-state NMR studies. Additionally, the efficiency of photoinduced energy transfer in these nanosheets was evidenced through photoborylation reactions and the generation of reactive oxygen species (ROS).
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Vanadium flow batteries (VFBs) face a challenge with the low reaction rates of the V(II)/V(III) redox couple, which limits the performance of VFBs. Additionally, the negative electrode in VFBs is often accompanied by the persistent hydrogen evolution reaction (HER), which is difficult to eliminate. Therefore, understanding the spatial distribution of activity on the negative electrode and the HER side reaction on the electrode surface is of critical importance. This study proposes a weak measurement imaging method to characterize the spatial distribution of surface activity and HER onset potential on the negative electrode in VFBs). This method enables the visualization and in situ detection of key parameters such as the absolute values of |ipa |, |ipc |, |∆E|, |ipc /ipa |, and the HER onset potential. By comparing three different types of graphite felts with varying activity levels, it validates the feasibility of this method. Furthermore, electrochemical stability tests are conducted to study the electrodes repeatability, uniformity, and durability. This method holds promise in guiding the design of electrodes with enhanced activity, good reversibility, minimized HER side reactions, and uniform distribution.
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INTRODUCTION: Whether 10-day short-course vonoprazan-amoxicillin dual therapy (VA-dual) is noninferior to the standard 14-day bismuth-based quadruple therapy (B-quadruple) against Helicobacter pylori eradication has not been determined. This trial aimed to compare the eradication rate, adverse events, and compliance of 10-day VA-dual regimen with standard 14-day B-quadruple regimen as first-line H. pylori treatment. METHODS: This prospective randomized clinical trial was performed at 3 institutions in eastern China. A total of 314 treatment-naive, H. pylori -infected patients were randomly assigned in a 1:1 ratio to either 10-day VA-dual group or 14-day B-quadruple group. Eradication success was determined by 13 C-urea breath test at least 4 weeks after treatment. Eradication rates, adverse events, and compliance were compared between groups. RESULTS: Eradication rates of VA-dual and B-quadruple groups were 86.0% and 89.2% ( P = 0.389), respectively, by intention-to-treat (ITT) analysis; 88.2% and 91.5% ( P = 0.338), respectively, by modified ITT analysis; and 90.8% and 91.3% ( P = 0.884), respectively, by per-protocol (PP) analysis. The efficacy of the VA-dual remained noninferior to B-quadruple therapy in all ITT, modified ITT, and PP analyses. The incidence of adverse events in the VA-dual group was significantly lower compared with that in the B-quadruple group ( P < 0.001). Poor compliance contributed to eradication failure in the VA-dual group ( P < 0.001), while not in the B-quadruple group ( P = 0.110). DISCUSSION: The 10-day VA-dual therapy provided satisfactory eradication rates of >90% (PP analysis) and lower rates of adverse events compared with standard 14-day B-quadruple therapy as first-line H. pylori therapy. TRAIL REGISTRATION NUMBER: ChiCTR2300070100.