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1.
Chin Med J (Engl) ; 2024 May 06.
Article in English | MEDLINE | ID: mdl-38710539

ABSTRACT

BACKGROUND: Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection. METHODS: A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with COVID-19-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2. RESULTS: Among the infected group, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs. 39.8% [92/231] vs. 37.5% [140/373], P <0.001). Psoriasis progression with lesions (adjusted odds ratio [OR] = 8.197, 95% confidence interval [95% CI] = 5.685-11.820, compared to no lesions), hypertension (adjusted OR = 1.582, 95% CI = 1.068-2.343), traditional systemic (adjusted OR = 1.887, 95% CI = 1.263-2.818), and nonsystemic treatment (adjusted OR = 1.602, 95% CI = 1.117-2.297) were found to be associated with exacerbation of psoriasis after SARS-CoV-2 infection, but not biologics (adjusted OR = 0.931, 95% CI = 0.680-1.274, compared to no treatment), according to multivariable logistic regression analysis. CONCLUSIONS: A reduced risk of psoriasis exacerbation after SARS-CoV-2 infection was observed with biologics compared to traditional systemic and nonsystemic treatments. Significant risk factors for exacerbation after infection were identified as existing psoriatic lesions and hypertension. TRIAL REGISTRATION: ClinicalTrials.gov (No. NCT05961605).

2.
Heliyon ; 10(10): e31071, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38803891

ABSTRACT

Objective: The Obturator Functioning Scale (OFS) is a scale without formal measures of validity in any language. This study aimed to translate and adapt the OFS from English to Chinese and check its reliability and validity in Chinese-speaking patients with obturator prostheses after cancer-related maxillectomy. Methods: The 15-item Chinese preversion of the OFS was completed by 133 patients in three tertiary stomatological hospitals. Of these, 41 completed it again one week after the first measurement. The patients also completed the Chinese version of the University of Washington quality of life scale (UW-QOL, Version 4). Results: Item 12 ("upper lip feels numb") was deleted to achieve a better statistical fit. The 14-item Chinese version of the OFS (OFS-Ch) demonstrated high internal consistency (Cronbach's alpha = 0.908). The test-retest reliability coefficients for most items exceeded 0.90, indicating substantial reproducibility. Confirmatory factor analysis found that the scale consisted of three correlated factors: 1) eating (four items), 2) speech (five items), and 3) other problems (five items). This explained 70.2 % of the total variance using exploratory factor analysis. The scale was significantly convergent and discriminant and could validly discriminate between patients with Brown I and IId maxillary defects. Conclusions: Our results showed that the OFS-Ch scale is a valid tool for evaluating oral dysfunction and satisfaction with appearance for patients with the obturator prosthesis and identifying those at risk of poor obturator function in clinical settings.

3.
Biomed Mater ; 19(4)2024 May 23.
Article in English | MEDLINE | ID: mdl-38697209

ABSTRACT

In the field of medicine, we often brave the unknown like interstellar explorers, especially when confronting the formidable opponent of hepatocellular carcinoma (HCC). The global burden of HCC remains significant, with suboptimal treatment outcomes necessitating the urgent development of novel drugs and treatments. While various treatments for liver cancer, such as immunotherapy and targeted therapy, have emerged in recent years, improving their transport and therapeutic efficiency, controlling their targeting and release, and mitigating their adverse effects remains challenging. However, just as we grope through the darkness, a glimmer of light emerges-nanotechnology. Recently, nanotechnology has attracted attention because it can increase the local drug concentration in tumors, reduce systemic toxicity, and has the potential to enhance the effectiveness of precision therapy for HCC. However, there are also some challenges hindering the clinical translation of drug-loaded nanoparticles (NPs). Just as interstellar explorers must overcome interstellar dust, we too must overcome various obstacles. In future researches, the design and development of nanodelivery systems for novel drugs treating HCC should be the first attention. Moreover, researchers should focus on the active targeting design of various NPs. The combination of the interventional therapies and drug-loaded NPs will greatly advance the process of precision HCC therapy.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Nanoparticles , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Liver Neoplasms/therapy , Humans , Nanoparticles/chemistry , Animals , Drug Delivery Systems , Antineoplastic Agents/chemistry , Antineoplastic Agents/administration & dosage , Nanotechnology/methods , Nanomedicine/methods , Immunotherapy/methods , Drug Carriers/chemistry
4.
Foods ; 13(9)2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38731662

ABSTRACT

Human milk oligosaccharides (HMO) that promote the growth of beneficial gut microbes in infants are abundant in human milk. Streptococcus, one of the dominant genera in human milk microbiota, is also highly prevalent in the infant gut microbiota, possibly due to its adeptness at utilizing HMOs. While previous studies have mainly focused on HMO interactions with gut bacteria like Bifidobacterium and Bacteroides spp., the interaction with Streptococcus spp. has not been fully explored. In this study, Streptococcus spp. was isolated from human milk and identified to exhibit extensive capabilities in utilizing HMOs. Their consumption rates of 2'-fucosyllactose (2'-FL), 6'-sialyllactose (6'-SL), and lacto-N-tetraose (LNT) closely matched those of Bifidobacterium longum subsp. infantis ATCC 15697. Furthermore, we assessed the safety-related genes in the genomes of the Streptococcus species capable of utilizing HMOs, revealing potential virulence and resistance genes. In addition, no haemolytic activity was observed. These findings expand the knowledge of metabolic interactions and networks within the microbiota of human milk and the early life human gut.

5.
J Headache Pain ; 25(1): 74, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38724948

ABSTRACT

BACKGROUND: Chronic migraine (CM) is a debilitating neurofunctional disorder primarily affecting females, characterized by central sensitization. Central sensitization refers to the enhanced response to sensory stimulation, which involves changes in neuronal excitability, synaptic plasticity, and neurotransmitter release. Environmental enrichment (EE) can increase the movement, exploration, socialization and other behaviors of mice. EE has shown promising effects in various neurological disorders, but its impact on CM and the underlying mechanism remains poorly understood. Therefore, the purpose of this study was to determine whether EE has the potential to serve as a cost-effective intervention strategy for CM. METHODS: A mouse CM model was successfully established by repeated administration of nitroglycerin (NTG). We selected adult female mice around 8 weeks old, exposed them to EE for 2 months, and then induced the CM model. Nociceptive threshold tests were measured using Von Frey filaments and a hot plate. The expression of c-Fos, calcitonin gene-related peptide (CGRP) and inflammatory response were measured using WB and immunofluorescence to evaluate central sensitization. RNA sequencing was used to find differentially expressed genes and signaling pathways. Finally, the expression of the target differential gene was investigated. RESULTS: Repeated administration of NTG can induce hyperalgesia in female mice and increase the expression of c-Fos and CGRP in the trigeminal nucleus caudalis (TNC). Early exposure of mice to EE reduced NTG-induced hyperalgesia in CM mice. WB and immunofluorescence revealed that EE inhibited the overexpression of c-Fos and CGRP in the TNC of CM mice and alleviated the inflammatory response of microglia activation. RNA sequencing analysis identified that several central sensitization-related signaling pathways were altered by EE. VGluT1, a key gene involved in behavior, internal stimulus response, and ion channel activity, was found to be downregulated in mice exposed to EE. CONCLUSION: EE can significantly ameliorate hyperalgesia in the NTG-induced CM model. The mechanisms may be to modulate central sensitization by reducing the expression of CGRP, attenuating the inflammatory response, and downregulating the expression of VGluT1, etc., suggesting that EE can serve as an effective preventive strategy for CM.


Subject(s)
Central Nervous System Sensitization , Disease Models, Animal , Hyperalgesia , Migraine Disorders , Nitroglycerin , Animals , Nitroglycerin/toxicity , Migraine Disorders/chemically induced , Migraine Disorders/metabolism , Hyperalgesia/chemically induced , Female , Central Nervous System Sensitization/drug effects , Central Nervous System Sensitization/physiology , Mice , Calcitonin Gene-Related Peptide/metabolism , Environment , Mice, Inbred C57BL
6.
J Imaging Inform Med ; 2024 May 13.
Article in English | MEDLINE | ID: mdl-38740662

ABSTRACT

Automatic retinal layer segmentation in optical coherence tomography (OCT) images is crucial for the diagnosis of ocular diseases. Currently, automatic retinal layer segmentation works well with normal OCT images. However, pigment epithelial detachment (PED) dramatically alters the retinal structure, causing blurred boundaries and partial disappearance of the Bruch's Membrane (BM), thus posing challenges to the segmentation. To tackle these problems, we propose a novel dual-path U-shaped network for simultaneous layer segmentation and boundary regression. This network first designs a feature interaction fusion (FIF) module to strengthen the boundary shape constraints in the layer path. To address the challenge posed by partial BM disappearance and boundary-blurring, we propose a layer boundary repair (LBR) module. This module aims to use contrastive loss to enhance the confidence of blurred boundary regions and refine the segmentation of layer boundaries through the re-prediction head. In addition, we introduce a novel bilateral threshold distance map (BTDM) designed for the boundary path. The BTDM serves to emphasize information within boundary regions. This map, combined with the updated probability map, culminates in topology-guaranteed segmentation results achieved through a topology correction (TC) module. We investigated the proposed network on two severely deformed datasets (i.e., OCTA-500 and Aier-PED) and one slightly deformed dataset (i.e., DUKE). The proposed method achieves an average Dice score of 94.26% on the OCTA-500 dataset, which was 1.5% higher than BAU-Net and outperformed other methods. In the DUKE and Aier-PED datasets, the proposed method achieved average Dice scores of 91.65% and 95.75%, respectively.

7.
Gut Microbes ; 16(1): 2347025, 2024.
Article in English | MEDLINE | ID: mdl-38693666

ABSTRACT

Helicobacter pylori (H. pylori) causes a diversity of gastric diseases. The host immune response evoked by H. pylori infection is complicated and can influence the development and progression of diseases. We have reported that the Group 2 innate lymphocytes (ILC2) were promoted and took part in building type-2 immunity in H. pylori infection-related gastric diseases. Therefore, in the present study, we aim to clarify how H. pylori infection induces the activation of ILC2. It was found that macrophages were necessary for activating ILC2 in H. pylori infection. Mechanistically, H. pylori infection up-regulated the expression of indoleamine 2,3-dioxygenase (IDO) in macrophages to induce M2 polarization, and the latter secreted the alarmin cytokine Thymic Stromal Lymphopoietin (TSLP) to arouse ILC2.


Subject(s)
Cytokines , Helicobacter Infections , Helicobacter pylori , Immunity, Innate , Macrophages , Helicobacter pylori/immunology , Macrophages/immunology , Macrophages/microbiology , Helicobacter Infections/immunology , Helicobacter Infections/microbiology , Animals , Mice , Cytokines/metabolism , Mice, Inbred C57BL , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics , Thymic Stromal Lymphopoietin , Lymphocytes/immunology , Humans
8.
Nanoscale ; 2024 May 24.
Article in English | MEDLINE | ID: mdl-38787730

ABSTRACT

The development of efficient and recyclable photocatalysts for organic synthesis is of great interest. This study presents the synthesis of triphenylamine-based porous aromatic frameworks (TPA-PAFs) in an alternating donor-acceptor (D-A) manner. The light absorption range and the optical band gaps of TPA-PAFs are effectively tuned by changing the electron acceptor units, which further determine their photocatalytic properties. As a result, TPA-PAFs exhibit excellent catalytic performance for the photosynthesis of benzimidazoles in high yields (up to 99%), broad substrate scope (18 examples), and good recyclability (up to 10 cycles). This work provides a feasible approach toward the facile design and synthesis of efficient and stable PAF-based photocatalysts, which further broadens the application of PAFs catalytic materials in photocatalytic organic synthesis.

9.
Analyst ; 149(11): 3064-3072, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38712864

ABSTRACT

Ratiometric near-infrared fluorescent pH probes with various pKa values were innovatively designed and synthesized based on cyanine with a diamine moiety. The photochemical properties of these probes were thoroughly evaluated. Among the series, IR-PHA exhibited an optimal pKa value of approximately 6.40, closely matching the pH of cancerous tissues. This feature is particularly valuable for real-time pH monitoring in both living cells and living mice. Moreover, when administered intravenously to tumor-bearing mice, IR-PHA demonstrated rapid and significant enhancement of near-infrared fluorescence and photoacoustic signals within the tumor region. This outcome underscores the probe's exceptional capability for dual-modal cancer imaging utilizing near-infrared fluorescence (NIRF) and photoacoustic (PA) modalities. Concurrently, the application of a continuous-wave near-infrared laser efficiently ablated cancer cells in vivo, attributed to the photothermal effect induced by IR-PHA. The results strongly indicate that IR-PHA is well-suited for NIRF/PA dual-modality imaging and photothermal therapy of tumors. This makes it a promising candidate for theranostic applications involving small molecules.


Subject(s)
Fluorescent Dyes , Infrared Rays , Photoacoustic Techniques , Photothermal Therapy , Animals , Photoacoustic Techniques/methods , Humans , Mice , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Fluorescent Dyes/radiation effects , Photothermal Therapy/methods , Neoplasms/diagnostic imaging , Neoplasms/therapy , Hydrogen-Ion Concentration , Cell Line, Tumor , Mice, Nude , Optical Imaging/methods , Female
10.
Comput Methods Programs Biomed ; 251: 108229, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38761413

ABSTRACT

BACKGROUND AND OBJECTIVE: Optical coherence tomography (OCT) is currently one of the most advanced retinal imaging methods. Retinal biomarkers in OCT images are of clinical significance and can assist ophthalmologists in diagnosing lesions. Compared with fundus images, OCT can provide higher resolution segmentation. However, image annotation at the bounding box level needs to be performed by ophthalmologists carefully and is difficult to obtain. In addition, the large variation in shape of different retinal markers and the inconspicuous appearance of biomarkers make it difficult for existing deep learning-based methods to effectively detect them. To overcome the above challenges, we propose a novel network for the detection of retinal biomarkers in OCT images. METHODS: We first address the issue of labeling cost using a novel weakly semi-supervised object detection method with point annotations which can reduce bounding box-level annotation efforts. To extend the method to the detection of biomarkers in OCT images, we propose multiple consistent regularizations for point-to-box regression network to deal with the shortage of supervision, which aims to learn more accurate regression mappings. Furthermore, in the subsequent fully supervised detection, we propose a cross-scale feature enhancement module to alleviate the detection problems caused by the large-scale variation of biomarkers. We also propose a dynamic label assignment strategy to distinguish samples of different importance more flexibly, thereby reducing detection errors due to the indistinguishable appearance of the biomarkers. RESULTS: When using our detection network, our regressor also achieves an AP value of 20.83 s when utilizing a 5 % fully labeled dataset partition, surpassing the performance of other comparative methods at 5 % and 10 %. Even coming close to the 20.87 % result achieved by Point DETR under 20 % full labeling conditions. When using Group R-CNN as the point-to-box regressor, our detector achieves 27.21 % AP in the 50 % fully labeled dataset experiment. 7.42 % AP improvement is achieved compared to our detection network baseline Faster R-CNN. CONCLUSIONS: The experimental findings not only demonstrate the effectiveness of our approach with minimal bounding box annotations but also highlight the enhanced biomarker detection performance of the proposed module. We have included a detailed algorithmic flow in the supplementary material.

11.
Nutrients ; 16(8)2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38674818

ABSTRACT

This study investigated the characteristics of Lactobacillus helveticus-derived whey-calcium chelate (LHWCC) and its effect on the calcium absorption and bone health of rats. Fourier-transform infrared spectroscopy showed that carboxyl oxygen atoms, amino nitrogen atoms, and phosphate ions were the major binding sites with calcium in LHWCC, which has a sustained release effect in simulated in vitro digestion. LHWCC had beneficial effects on serum biochemical parameters, bone biomechanics, and the morphological indexes of the bones of calcium-deficient rats when fed at a dose of 40 mg Ca/kg BW for 7 weeks. In contrast to the inorganic calcium supplement, LHWCC significantly upregulated the gene expression of transient receptor potential cation V5 (TRPV5), TRPV6, PepT1, calcium-binding protein-D9k (Calbindin-D9k), and a calcium pump (plasma membrane Ca-ATPase, PMCA1b), leading to promotion of the calcium absorption rate, whereas Ca3(PO4)2 only upregulated the TRPV6 channel in vivo. These findings illustrate the potential of LHWCC as an organic calcium supplement.


Subject(s)
Bone and Bones , Calcium , Lactobacillus helveticus , Animals , Rats , Calcium/metabolism , Bone and Bones/metabolism , Bone and Bones/drug effects , Male , Rats, Sprague-Dawley , Whey/chemistry , TRPV Cation Channels/metabolism , TRPV Cation Channels/genetics , Calcium, Dietary/pharmacology , Calcium, Dietary/administration & dosage , Dietary Supplements , Calcium Channels/metabolism , Calcium Chelating Agents/pharmacology
12.
Materials (Basel) ; 17(8)2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38673193

ABSTRACT

The industrial byproduct gypsum is a general term for byproducts discharged from industrial production with calcium sulfate as the main ingredient. Due to the high number of impurities and production volume, the industrial byproduct gypsum is underutilized, leading to serious environmental problems. At present, only desulfurization gypsum and phosphogypsum have been partially utilized in cementitious materials, cement retarders, etc., while the prospects for the utilization of other byproduct gypsums remain worrying. This paper mainly focuses on the sources and physicochemical properties of various types of gypsum byproducts and summarizes the application scenarios of various gypsums in construction materials. Finally, some suggestions are proposed to solve the problem of the industrial byproduct gypsum. This review is informative for solving the environmental problems caused by gypsum accumulation.

13.
Article in English | MEDLINE | ID: mdl-38657655

ABSTRACT

An essential factor in tooth nutritional deficits and aberrant root growth is pulp necrosis. Removing inflammatory or necrotic pulp tissue and replacing it with an inert material are the most widely used therapeutic concepts of endodontic treatment. However, pulp loss can lead to discoloration, increased fracture risk, and the reinfection of the damaged tooth. It is now anticipated that the pulp-dentin complex will regenerate through a variety of application methods based on human dental pulp stem cells (hDPSC). In order to create a photo-cross-linked gelatinized methacrylate hydrogel, GelMA/EUO-CDs-E (ECE), that is biodegradable and injectable for application, we created a novel nanoassembly of ECE based on eucommia carbon dots (EUO-CDs) and epigallocatechin gallate (EGCG). We then loaded it onto gelatin methacryloyl (GelMA) hydrogel. We have evaluated the material and examined its in vivo and in vitro angiogenesis-promoting potential as well as its dentin differentiation-enabling characteristics. The outcomes of the experiment demonstrated that GelMA/ECE was favorable to cell proliferation and enhanced hDPSC's capacity for angiogenesis and dentin differentiation. The regeneration of vascular-rich pulp-like tissues was found to occur in vivo when hDPSC-containing GelMA/ECE was injected into cleaned human root segments (RS) for subcutaneous implantation in nude mice. This suggests that the injectable bioscaffold is appropriate for clinical use in pulp regenerative medicine.

14.
Adv Sci (Weinh) ; : e2400101, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38647267

ABSTRACT

Hydrogen-bonded organic frameworks (HOFs) are emerging porous materials that show high structural flexibility, mild synthetic conditions, good solution processability, easy healing and regeneration, and good recyclability. Although these properties give them many potential multifunctional applications, their frameworks are unstable due to the presence of only weak and reversible hydrogen bonds. In this work, the development history and synthesis methods of HOFs are reviewed, and categorize their structural design concepts and strategies to improve their stability. More importantly, due to the significant potential of the latest HOF-related research for addressing energy and environmental issues, this work discusses the latest advances in the methods of energy storage and conversion, energy substance generation and isolation, environmental detection and isolation, degradation and transformation, and biological applications. Furthermore, a discussion of the coupling orientation of HOF in the cross-cutting fields of energy and environment is presented for the first time. Finally, current challenges, opportunities, and strategies for the development of HOFs to advance their energy and environmental applications are discussed.

15.
Biomicrofluidics ; 18(2): 021505, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38659428

ABSTRACT

Acoustohydrodynamic micromixers offer excellent mixing efficiency, cost-effectiveness, and flexible controllability compared with conventional micromixers. There are two mechanisms in acoustic micromixers: indirect influence by induced streamlines, exemplified by sharp-edge micromixers, and direct influence by acoustic waves, represented by surface acoustic wave micromixers. The former utilizes sharp-edge structures, while the latter employs acoustic wave action to affect both the fluid and its particles. However, traditional micromixers with acoustic bubbles achieve significant mixing performance and numerous programmable mixing platforms provide excellent solutions with wide applicability. This review offers a comprehensive overview of various micromixers, elucidates their underlying principles, and explores their biomedical applications. In addition, advanced programmable micromixing with impressive versatility, convenience, and ability of cross-scale operations is introduced in detail. We believe this review will benefit the researchers in the biomedical field to know the micromixers and find a suitable micromixing method for their various applications.

16.
Materials (Basel) ; 17(7)2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38612220

ABSTRACT

The disposal of electroplating sludge (ES) is a major challenge for the sustainable development of the electroplating industry. ESs have a significant environmental impact, occupying valuable land resources and incurring high treatment costs, which increases operational expenses for companies. Additionally, the high concentration of hazardous substances in ES poses a serious threat to both the environment and human health. Despite extensive scholarly research on the harmless treatment and resource utilization of ES, current technology and processes are still unable to fully harness its potential. This results in inefficient resource utilization and potential environmental hazards. This article analyzes the physicochemical properties of ES, discusses its ecological hazards, summarizes research progress in its treatment, and elaborates on methods such as solidification/stabilization, heat treatment, wet metallurgy, pyrometallurgy, biotechnology, and material utilization. It provides a comparative summary of different treatment processes while also discussing the challenges and future development directions for technologies aimed at effectively utilizing ES resources. The objective of this text is to provide useful information on how to address the issue of ES treatment and promote sustainable development in the electroplating industry.

17.
Article in English | MEDLINE | ID: mdl-38561530

ABSTRACT

Biochar has effect on phosphorus adsorption, release, and transformation. This study compared the influence of biochar derived from animal (AB) and plant (PB) during paper mill sludge composting. Results indicated AB not only accelerated sludge decomposition but also had significantly higher levels of available phosphorus (AP) than PB and CK (no biochar), with AP contents in the order of AB > PB > CK. Compared to CK, AB was found to increase the relative abundance of thermophilic bacteria, and PB diversified the microbial community. Based on Pearson and RDA results, TOC/TN ratio (C/N) and organic matter (OM) explained above 50% of the variance in microbial community and phosphorus fractions. Thermophilic bacteria with high levels of OM and C/N promoted the conversion among labile and moderately labile organic phosphorus, moderately labile inorganic phosphorus, and AP. Biochar could enhance the AP conversion pathway, leading to increased levels of AP.

18.
J Cancer ; 15(7): 1837-1847, 2024.
Article in English | MEDLINE | ID: mdl-38434977

ABSTRACT

Objective: This study aimed to investigate the prognostic effect of sarcopenia on primary hepatocellular carcinoma (HCC) patients after transcatheter arterial chemoembolization (TACE). Methods: This retrospective study enrolled 265 patients diagnosed with HCC who underwent TACE between April 2014 and February 2021. The patients were divided into two groups: the sarcopenia group (n=133) and the non-sarcopenia group (n=132). The study analyzed the differences in overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier curves. The independent risk factors for OS and PFS were determined using univariate and multivariate Cox regression analysis. Based on these factors, the study constructed a prognostic risk grading system. Results: At 3 and 6 months post-TACE, the prognoses of the sarcopenia group were worse than that of the non-sarcopenia group according to the mRECIST criteria. Kaplan-Meier curves showed that the cumulative OS and PFS rate in the non-sarcopenia group were significantly higher compared to the sarcopenia group (HR=3.319, 95%CI: 2.283-4.824, Log-rank P < 0.001; HR=0.631, 95%CI: 0.486-0.820, Log-rank P < 0.001). Sarcopenia, maximal tumor diameter, and AFP ≥ 200 ng/mL were independent risk factors for OS and PFS. The prognostic risk grading system based on sarcopenia, AFP ≥ 200 ng/mL, and maximal tumor diameter≥8.9 cm showed significant differences in prognosis between risk groups. Conclusion: Sarcopenia had excellent predictive value for OS and PFS in patients after TACE, and AFP ≥ 200 ng/mL and maximal tumor diameter were also independent risk factors for a poor prognosis. The prognostic risk grading system based on sarcopenia, AFP, and maximal tumor diameter had good guiding value for the prognosis of patients.

19.
ACS Cent Sci ; 10(2): 344-357, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38435523

ABSTRACT

A large variety of dietary phytochemicals has been shown to improve thrombosis and stroke outcomes in preclinical studies. Many of these compounds feature electrophilic functionalities that potentially undergo covalent addition to the sulfhydryl side chain of cysteine residues within proteins. However, the impact of such covalent modifications on the platelet activity and function remains unclear. This study explores the irreversible engagement of 23 electrophilic phytochemicals with platelets, unveiling the unique antiplatelet selectivity of sulforaphane (SFN). SFN impairs platelet responses to adenosine diphosphate (ADP) and a thromboxane A2 receptor agonist while not affecting thrombin and collagen-related peptide activation. It also substantially reduces platelet thrombus formation under arterial flow conditions. Using an alkyne-integrated probe, protein disulfide isomerase A6 (PDIA6) was identified as a rapid kinetic responder to SFN. Mechanistic profiling studies revealed SFN's nuanced modulation of PDIA6 activity and substrate specificity. In an electrolytic injury model of thrombosis, SFN enhanced the thrombolytic activity of recombinant tissue plasminogen activator (rtPA) without increasing blood loss. Our results serve as a catalyst for further investigations into the preventive and therapeutic mechanisms of dietary antiplatelets, aiming to enhance the clot-busting power of rtPA, currently the only approved therapeutic for stroke recanalization that has significant limitations.

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