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1.
Mater Horiz ; 2024 May 15.
Article in English | MEDLINE | ID: mdl-38747452

ABSTRACT

The development of effective and novel flame retardants has been attracting considerable attention in extenuating the fire threat of flammable polymer materials including the widely-used epoxy resins. In this work, we pioneeringly report the construction of transition-metal-substituted polyoxometalate-ionic liquids (tmsPOM-ILs) as effective flame retardants, which consist of tetra-metal-containing POMs ([M4(H2O)2(PW9O34)2]10-, M4P2, M = Ni, Cu) anions and tetra-n-heptylammonium [(n-C7H15)4N+, THPA] cations. The resulting tmsPOM-ILs exhibited remarkably improved fire-safety of the epoxy resin (EP) matrix and even at a loading amount of as low as 3 wt%, the flame retardancy efficiency was even higher than that of commercial flame retardants (aluminum hydroxide (ATH), triphenyl phosphate (TPP), and decabromodiphenyl ethane (DBDPE)). Physicochemical and mechanistic studies revealed that the remarkable flame retardancy performance of the tmsPOM-ILs reported is due to their excellent epoxy matrix compatibility and remarkable catalytic charring ability. This work opens up a brand-new research direction of developing next-generation compatible and effective tmsPOM-based molecular flame retardants at the molecular level.

2.
Ren Fail ; 46(1): 2350235, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38721924

ABSTRACT

Increasing evidence suggests that peritoneal fibrosis induced by peritoneal dialysis (PD) is linked to oxidative stress. However, there are currently no effective interventions for peritoneal fibrosis. In the present study, we explored whether adding caffeic acid phenethyl ester (CAPE) to peritoneal dialysis fluid (PDF) improved peritoneal fibrosis caused by PD and explored the molecular mechanism. We established a peritoneal fibrosis model in Sprague-Dawley rats through intraperitoneal injection of PDF and lipopolysaccharide (LPS). Rats in the PD group showed increased peritoneal thickness, submesothelial collagen deposition, and the expression of TGFß1 and α-SMA. Adding CAPE to PDF significantly inhibited PD-induced submesothelial thickening, reduced TGFß1 and α-SMA expression, alleviated peritoneal fibrosis, and improved the peritoneal ultrafiltration function. In vitro, peritoneal mesothelial cells (PMCs) treated with PDF showed inhibition of the AMPK/SIRT1 pathway, mitochondrial membrane potential depolarization, overproduction of mitochondrial reactive oxygen species (ROS), decreased ATP synthesis, and induction of mesothelial-mesenchymal transition (MMT). CAPE activated the AMPK/SIRT1 pathway, thereby inhibiting mitochondrial membrane potential depolarization, reducing mitochondrial ROS generation, and maintaining ATP synthesis. However, the beneficial effects of CAPE were counteracted by an AMPK inhibitor and siSIRT1. Our results suggest that CAPE maintains mitochondrial homeostasis by upregulating the AMPK/SIRT1 pathway, which alleviates oxidative stress and MMT, thereby mitigating the damage to the peritoneal structure and function caused by PD. These findings suggest that adding CAPE to PDF may prevent and treat peritoneal fibrosis.


Subject(s)
AMP-Activated Protein Kinases , Caffeic Acids , Peritoneal Dialysis , Peritoneal Fibrosis , Phenylethyl Alcohol , Rats, Sprague-Dawley , Sirtuin 1 , Animals , Peritoneal Fibrosis/etiology , Peritoneal Fibrosis/metabolism , Peritoneal Fibrosis/prevention & control , Sirtuin 1/metabolism , Phenylethyl Alcohol/analogs & derivatives , Phenylethyl Alcohol/pharmacology , Caffeic Acids/pharmacology , Caffeic Acids/therapeutic use , Rats , Male , AMP-Activated Protein Kinases/metabolism , Peritoneal Dialysis/adverse effects , Mitochondria/drug effects , Mitochondria/metabolism , Disease Models, Animal , Signal Transduction/drug effects , Peritoneum/pathology , Peritoneum/drug effects , Peritoneum/metabolism , Homeostasis/drug effects , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Transforming Growth Factor beta1/metabolism , Membrane Potential, Mitochondrial/drug effects , Dialysis Solutions
3.
Expert Rev Vaccines ; 23(1): 498-509, 2024.
Article in English | MEDLINE | ID: mdl-38695310

ABSTRACT

BACKGROUND: Vaccination remains the cornerstone of defense against COVID-19 globally. This study aims to assess the safety and immunogenicity profile of innovative vaccines LYB001. RESEARCH DESIGN AND METHODS: This was a randomized, double-blind, parallel-controlled trial, in 100 healthy Chinese adults (21 to 72 years old). Three doses of 30 or 60 µg of SARS-CoV-2 RBD-based VLP vaccine (LYB001), or the SARS-CoV-2 RBD-based protein subunit vaccine (ZF2001, control group) were administered with a 28-day interval. Differences in the incidence of adverse events (AEs) and indicators of humoral and cellular immunity among the different groups were measured. RESULTS: No severe adverse events were confirmed to be vaccine-related, and there was no significant difference in the rate of adverse events between the LYB001 and control group or the age subgroups (p > 0.05). The LYB001 groups had significantly higher or comparable levels of seroconversion rates, neutralization antibody, S protein-binding antibody, and cellular immunity after whole vaccination than the control group. CONCLUSIONS: Our findings support that LYB001 developed on the VLP platform is safe and well tolerated with favorable immunogenicity for fundamental vaccination in healthy adults. Therefore, further larger-scale clinical studies are warranted. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT05552573).


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Humans , Adult , Middle Aged , Double-Blind Method , COVID-19 Vaccines/immunology , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/administration & dosage , Male , Female , Antibodies, Viral/blood , Aged , Young Adult , Antibodies, Neutralizing/blood , SARS-CoV-2/immunology , COVID-19/prevention & control , COVID-19/immunology , Immunogenicity, Vaccine , Vaccines, Virus-Like Particle/immunology , Vaccines, Virus-Like Particle/adverse effects , Vaccines, Virus-Like Particle/administration & dosage , Immunity, Cellular , China , Immunity, Humoral , Spike Glycoprotein, Coronavirus/immunology , Vaccination/methods , Vaccines, Subunit/immunology , Vaccines, Subunit/adverse effects , Vaccines, Subunit/administration & dosage , East Asian People
4.
Front Oncol ; 14: 1350043, 2024.
Article in English | MEDLINE | ID: mdl-38715782

ABSTRACT

Renal cell carcinoma (RCC) is the most common renal tumor, with lung, bone, and liver being the primary sites of metastasis. Thyroid metastasis, on the other hand, is relatively uncommon. Metastatic tumors in the thyroid gland typically manifest as multiple or isolated nodules, which can be easily overlooked due to the lack of specific clinical and imaging features. However, the identification of thyroid metastasis suggests the presence of systemic metastasis and is indicative of a poor prognosis for patients. In this paper, we present two cases of thyroid metastasis following nephrectomy, with the objective of enhancing understanding among medical community regarding the diagnosis and treatment of thyroid metastasis originating from renal cell carcinoma. By raising awareness about this phenomenon, we emphasize the importance of early detection and diagnosis to improve patient prognoses. The implementation of standardized treatment protocols at the earliest possible stage is also emphasized. Through this research, we aim to contribute to the early identification and management of thyroid metastasis in patients with renal cell carcinoma, ultimately leading to improved outcomes.

5.
Front Neurol ; 15: 1361063, 2024.
Article in English | MEDLINE | ID: mdl-38746656

ABSTRACT

Background: Parkinson's disease (PD) is characterized by a range of motor symptoms as well as documented sensory dysfunction. This sensory dysfunction can present itself either as a "pure" sensory disturbance or as a consequence of sensory-motor integration within the central nervous system. This study aims to investigate changes in the functional connectivity of the primary somatosensory cortex (S1) and its clinical significance in Parkinson's disease (PD), an area that has received limited attention in previous neuroimaging studies. Methods: This study included thirty-three patients with PD and thirty-four healthy controls (HCs). Clinical evaluations were conducted to assess the clinical manifestations, severity, and functional capacity of all the patients. Resting-state functional MRI (fMRI) was employed to evaluate the functional connectivity of six paired S1 subregions in the participants. Seed-based correlation (SBC) analysis was utilized to construct the correlation matrix among the subregions and to generate connectivity maps between the subregions and the remaining brain voxels. Finally, the study employed partial least-squares (PLS) correlation analysis to investigate the association between modified functional connectivity and clinical characteristics in PD patients. Results: In the correlation matrix, patients with PD demonstrated a notable decrease in functional connectivity across various S1 subregions in comparison to HCs (p < 0.001, corrected using network-based methods). In connectivity maps, hypo-connectivity was primarily observed in the sensorimotor network as common patterns (p < 0.001, corrected for false discovery rate) and in the default mode network (DMN) as distinct patterns. Moreover, this study identified a negative association between the correlation matrix within S1 subregions and the scores for axial symptoms and postural instability/gait difficulty (PIGD) in PD patients. Nevertheless, a direct relationship between the connectivity maps of S1 subregions and clinical assessment scales was not established. Conclusion: This study offers novel insights into the neurobiological mechanisms that contribute to S1 dysfunction in PD, highlighting the significant involvement of S1 hypo-connectivity in the motor disturbances observed in PD patients.

6.
Transl Cancer Res ; 13(3): 1382-1393, 2024 Mar 31.
Article in English | MEDLINE | ID: mdl-38617513

ABSTRACT

Background: Esophageal adenocarcinoma (EAC) is an aggressive cancer with poor prognosis. Thus, this study aimed to identify a prognostic molecular signature to predict the overall survival (OS) of patients with EAC. Methods: The mRNA microarray data sets GSE13898 and GSE26886 were downloaded from the Gene Expression Omnibus (GEO) database. RNA sequencing profile and clinical data of EAC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) between EAC tissues and adjacent non-cancerous tissues were obtained using R software. DEGs associated with prognosis of OS were assessed by univariate Cox analysis, and a prognostic signature was built using stepwise multivariate Cox analysis. Time-dependent receiver operating characteristic (ROC) analysis and stratification analysis were conducted to evaluate its predictive performance. Functional enrichment analysis was performed for genes co-expressed with the signature to explore its biological functions in EAC. Results: A total of 336 genes were identified to be differentially expressed between EAC tissues and adjacent non-cancerous tissues. After univariate and multivariate Cox regression analysis, four genes (ALAD, ABLIM3, IL17RB and IFI6) were screened out to construct a prognostic signature. According to this signature, patients could be assigned into high-risk and low-risk group with significantly different OS (P=4.92e-05<0.0001). Multivariate Cox regression analysis suggested that the four-gene signature served as an independent factor in OS prediction. In the time-dependent ROC analysis, the areas under the curves (AUCs) were 0.804, 0.792 and 0.695 for 1-, 3- and 5-year survival prediction, respectively, suggesting a good performance. Functional enrichment analysis showed that the signature was mainly clustered in cell proliferation related biological processes or pathways. Conclusions: The four-gene signature identified in the current study may be a potential prognostic factor for predicting OS of EAC patients.

7.
Heliyon ; 10(7): e29267, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38623213

ABSTRACT

Objectives: Lymphovascular invasion serves as a crucial prognostic indicator in invasive breast cancer, influencing treatment decisions. We aimed to develop a machine learning model utilizing optimal volumes of interest extracted from multisequence magnetic resonance images to predict lymphovascular invasion in patients with invasive breast cancer. Materials and methods: This study comprised 191 patients postoperatively diagnosed with invasive breast cancer through multi-sequence magnetic resonance imaging. Independent predictors were identified through univariate and multivariate logistic regression analyses, culminating in the construction of a clinical model. Radiomic features were extracted from multi-sequence magnetic resonance imaging images across various volume of interest scales (-2 mm, entire, +2 mm, +4 mm, and +6 mm). Subsequently, various radiomic models were developed using machine learning model algorithms, including logistic regression, support vector machine, k-nearest neighbor, gradient boosting machine, classification and regression tree, and random forest. A hybrid model was then formulated, amalgamating optimal radiomic and clinical models. Results: The area under the curve of the clinical model was 0.757. Among the radiomic models, the most efficient diagnosis was achieved by the k-nearest neighbor-based radiomics-volume of interest (+2 mm), resulting in an area under the curve of 0.780. The hybrid model, integrating the k-nearest neighbor-based radiomics-volume of interest (+2 mm), and the clinical model surpassed the individual clinical and radiomics models, exhibiting a superior area under the curve of 0.864. Conclusion: Utilizing a hybrid approach integrating clinical data and multi-sequence magnetic resonance imaging-derived radiomics models based on the multiscale tumor region volume of interest (+2 mm) proved effective in determining lymphovascular invasion status in patients with invasive breast cancer. This innovative methodology may offer valuable insights for treatment planning and disease management.

8.
ACS Biomater Sci Eng ; 10(5): 2841-2862, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38644736

ABSTRACT

Cancer is a severe threat to humans, as it is the second leading cause of death after cardiovascular diseases and still poses the biggest challenge in the world of medicine. Due to its higher mortality rates and resistance, it requires a more focused and productive approach to provide the solution for it. Many therapies promising to deliver favorable results, such as chemotherapy and radiotherapy, have come up with more negatives than positives. Therefore, a new class of medicinal solutions and a more targeted approach is of the essence. This review highlights the alluring properties, configurations, and self-assembly of peptide molecules which benefit the traditional approach toward cancer therapy while sparing the healthy cells in the process. As targeted drug delivery systems, self-assembled peptides offer a wide spectrum of conjugation, biocompatibility, degradability-controlled responsiveness, and biomedical applications, including cancer treatment and cancer imaging.


Subject(s)
Neoplasms , Peptides , Humans , Neoplasms/drug therapy , Neoplasms/diagnostic imaging , Peptides/therapeutic use , Peptides/chemistry , Drug Delivery Systems/methods , Animals , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology
9.
Aging (Albany NY) ; 16(8): 6757-6772, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38656882

ABSTRACT

USP15, a pivotal member of the deubiquitinase family, plays a crucial role in orchestrating numerous vital biological processes, including the regulation of NF-κB signaling pathway and deubiquitination of proto-oncogenes. In various cancers, USP15 has been validated to exhibit up-regulated expression, impacting the initiation and progression of cancer. However, its precise mechanism in bladder cancer remains elusive. Our study shed light on the significant overexpression of USP15 in bladder cancer cells compared to normal bladder cells, correlating with a poorer prognosis for bladder cancer patients. Strikingly, attenuation of USP15 expression greatly attenuated the proliferation, migration, and invasion of bladder cancer cells. Moreover, upregulation of USP15 was found to drive cancer progression through the activation of the NF-κB signaling pathway. Notably, USP15 directly deubiquitinates BRCC3, heightening its expression level, and subsequent overexpression of BRCC3 counteracted the antitumoral efficacy of USP15 downregulation. Overall, our findings elucidated the carcinogenic effects of USP15 in bladder cancer, primarily mediated by the excessive activation of the NF-κB signaling pathway, thereby promoting tumor development. These results underscore the potential of USP15 as a promising therapeutic target for bladder cancer in the future.


Subject(s)
Cell Proliferation , Disease Progression , NF-kappa B , Signal Transduction , Ubiquitin-Specific Proteases , Urinary Bladder Neoplasms , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/genetics , Humans , NF-kappa B/metabolism , Ubiquitin-Specific Proteases/metabolism , Ubiquitin-Specific Proteases/genetics , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Cell Movement/genetics , Ubiquitination , Animals
10.
Neurol Res ; 46(5): 416-425, 2024 May.
Article in English | MEDLINE | ID: mdl-38577889

ABSTRACT

OBJECTIVE: Previous studies have revealed that Propane-2-sulfonic acid octadec-9-enyl-amide(N15) exerts a protective role in the inflammatory response after ischemic stroke and in neuronal damage. However, little is known about N15 in Alzheimer's disease (AD). The aim of this study was to investigate the effects of N15 on AD and explore the underlying molecular mechanism. METHODS: AD mice model was established by lateral ventricular injection with Aß25-35. N15 was daily intraperitoneal administered for 28 days. Morris Water Maze was used to evaluate the neurocognitive function of the mice. The expression of PPARα/γ, brain-derived neurotrophic factor (BDNF), Neurotrophin-3 (NT3), ADAM10, PS1 and BACE1 were measured by qPCR. Aß amyloid in the hippocampus was measured by Congo red assay. Toluidine blue staining was used to detect the neuronal apoptosis. Protein levels of ADAM10, PS1 and BACE1 were determined using immunoblotting. RESULTS: N15 treatment significantly reduced neurocognitive dysfunction, which also significantly activated the expression of PPARα/γ at an optimal dose of 200 mg/kg. Administration of N15 alleviated the formation of Aß amyloid in the hippocampus of AD mice, enhanced the BDNF mRNA expression, decreased the mRNA and protein levels of PS1 and BACE1, upregulated ADAM10 mRNA and protein levels. CONCLUSION: N15 exerts its neuroprotective effects through the activation of PPARα/γ and may be a potential drug for the treatment of AD.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Disease Models, Animal , Hippocampus , PPAR alpha , PPAR gamma , Animals , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , PPAR gamma/agonists , PPAR gamma/metabolism , PPAR alpha/agonists , PPAR alpha/metabolism , Male , Amyloid beta-Peptides/metabolism , Mice , Hippocampus/drug effects , Hippocampus/metabolism , Hippocampus/pathology , Sulfonic Acids/pharmacology , Peptide Fragments , Maze Learning/drug effects , Neuroprotective Agents/pharmacology , Memory/drug effects , Brain-Derived Neurotrophic Factor/metabolism , Amyloid Precursor Protein Secretases/metabolism , Mice, Inbred C57BL
11.
Medicine (Baltimore) ; 103(14): e37569, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38579100

ABSTRACT

BACKGROUND: Vomiting is one of the most common adverse events of chemotherapy. The purpose of this study was to systematically review the clinical efficacy of acupoint injection of metoclopramide in the treatment of post-chemotherapy vomiting. METHODS: We searched 4 general English databases and 4 conventional Chinese databases, all with a time frame from database creation to December 2022. The retrieved clinical trials of acupoint injection of metoclopramide for post-chemotherapy vomiting were then subjected to meta-analysis and trial sequential analysis. RESULTS: A total of 12 studies were included, with a total sample size of 965 cases. Meta-analysis showed that acupoint injection of metoclopramide was effective in improving anti-vomiting effective rate [odds ratio = 5.67, 95% confidence interval = (3.80,8.47), P < .00001] compared with intramuscular/intravenous injection, and trial sequential analysis showed that this benefit was conclusive. Subgroup analysis demonstrated that acupoint injection significantly improved the anti-vomiting effective rate at doses of 10 mg qd, 20 mg qd, and 30 mg qd, as well as at durations of 1 day and 5 days. Subgroup analysis also indicated that injection at the Zusanli acupoint significantly increased the anti-vomiting effective rate, while injection at the Neiguan acupoint had an anti-vomiting effective rate comparable to that of the control group. Harbord regression showed no significant publication bias (P = .730). CONCLUSION: Acupoint injection of metoclopramide for post-chemotherapy vomiting is more effective than intramuscular and intravenous injections and is not limited by dose or duration of treatment, which may be the preferred way of administration.


Subject(s)
Acupuncture Therapy , Metoclopramide , Humans , Metoclopramide/therapeutic use , Acupuncture Points , Vomiting/chemically induced , Vomiting/drug therapy , Treatment Outcome
12.
Brain Sci ; 14(4)2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38672045

ABSTRACT

In the past few years, significant advancements in microscopic imaging technology have led to the production of numerous high-resolution images capturing brain neurons at the micrometer scale. The reconstructed structure of neurons from neuronal images can serve as a valuable reference for research in brain diseases and neuroscience. Currently, there lacks an accurate and efficient method for neuron reconstruction. Manual reconstruction remains the primary approach, offering high accuracy but requiring significant time investment. While some automatic reconstruction methods are faster, they often sacrifice accuracy and cannot be directly relied upon. Therefore, the primary goal of this paper is to develop a neuron reconstruction tool that is both efficient and accurate. The tool aids users in reconstructing complete neurons by calculating the confidence of branches during the reconstruction process. The method models the neuron reconstruction as multiple Markov chains, and calculates the confidence of the connections between branches by simulating the reconstruction artifacts in the results. Users iteratively modify low-confidence branches to ensure precise and efficient neuron reconstruction. Experiments on both the publicly accessible BigNeuron dataset and a self-created Whole-Brain dataset demonstrate that the tool achieves high accuracy similar to manual reconstruction, while significantly reducing reconstruction time.

13.
Genes (Basel) ; 15(4)2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38674339

ABSTRACT

The precise identification of splice sites is essential for unraveling the structure and function of genes, constituting a pivotal step in the gene annotation process. In this study, we developed a novel deep learning model, DRANetSplicer, that integrates residual learning and attention mechanisms for enhanced accuracy in capturing the intricate features of splice sites. We constructed multiple datasets using the most recent versions of genomic data from three different organisms, Oryza sativa japonica, Arabidopsis thaliana and Homo sapiens. This approach allows us to train models with a richer set of high-quality data. DRANetSplicer outperformed benchmark methods on donor and acceptor splice site datasets, achieving an average accuracy of (96.57%, 95.82%) across the three organisms. Comparative analyses with benchmark methods, including SpliceFinder, Splice2Deep, Deep Splicer, EnsembleSplice, and DNABERT, revealed DRANetSplicer's superior predictive performance, resulting in at least a (4.2%, 11.6%) relative reduction in average error rate. We utilized the DRANetSplicer model trained on O. sativa japonica data to predict splice sites in A. thaliana, achieving accuracies for donor and acceptor sites of (94.89%, 94.25%). These results indicate that DRANetSplicer possesses excellent cross-organism predictive capabilities, with its performance in cross-organism predictions even surpassing that of benchmark methods in non-cross-organism predictions. Cross-organism validation showcased DRANetSplicer's excellence in predicting splice sites across similar organisms, supporting its applicability in gene annotation for understudied organisms. We employed multiple methods to visualize the decision-making process of the model. The visualization results indicate that DRANetSplicer can learn and interpret well-known biological features, further validating its overall performance. Our study systematically examined and confirmed the predictive ability of DRANetSplicer from various levels and perspectives, indicating that its practical application in gene annotation is justified.


Subject(s)
Arabidopsis , Oryza , RNA Splice Sites , Arabidopsis/genetics , RNA Splice Sites/genetics , Humans , Oryza/genetics , Deep Learning , Software , RNA Splicing , Computational Biology/methods
14.
Public Health Nurs ; 41(3): 476-486, 2024.
Article in English | MEDLINE | ID: mdl-38468509

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer mortality. HCC has high morbidity, high mortality, and low survival rates. Screening is one of the most significant methods of lowering incidence and death while also increasing survival. OBJECTIVES: The aim of this study was to identify the facilitators and barriers to participation in HCC screening among high-risk populations. METHODS: A comprehensive and systematic search was undertaken in PubMed, Web of Science, MEDLINE, EMBACE, EBSCOhost and the Cochrane Library. A combination of synonyms of the keywords including HCC, screening, factors and adherence were used for searching. Studies addressing the facilitators and barriers to HCC screening compliance in at-risk individuals were included. Data were synthesized using Review Manager version 5.4. A random/fixed effects model meta-analysis was performed to estimate the pooled data and expressed with odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of seven articles met the inclusion criteria. Qualitative (n = 1) and quantitative (n = 6) studies using various types of surgery were conducted. The most commonly mentioned barriers were insufficient knowledge and awareness of HCC screening, unawareness of the necessity for early detection of HCC and lack of physician recommendation. A meta-analysis of seven studies showed that individuals with a family history of HCC increased screening uptake by nearly three times (OR: 2.69, 95% CI: 1.93, 3.75). Other most frequently reported facilitators include age, education level, and perceived risk et al. CONCLUSIONS: Many barriers to HCC screening were found. Meanwhile, this review points out that improving the awareness of high-risk populations toward HCC screening is expected to enhance compliance, thereby promoting early diagnosis of liver cancer, reducing mortality, and alleviating the burden of HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/diagnosis , Liver Neoplasms/pathology , Incidence
15.
Int J Clin Pharmacol Ther ; 62(5): 222-228, 2024 May.
Article in English | MEDLINE | ID: mdl-38431833

ABSTRACT

OBJECTIVE: Azvudine is an effective treatment for patients infected with common COVID-19. However, physicians have reported a series of adverse reactions, including multiple cases of liver injury, caused by azvudine in clinical practice. This study assessed the incidence, clinical features, and associated risk factors of liver injury induced by azvudine in real-world settings, offering guidance for safe clinical use. MATERIALS AND METHODS: This study utilized the Chinese Hospital Pharmacovigilance System (CHPS) to retrospectively analyze the treatment of COVID-19 patients with azvudine at Changsha Central Hospital from December 19, 2022, to June 6, 2023. A case-control study was conducted to analyze the occurrence of azvudine-induced liver injury in COVID-19 patients who triggered a CHPS alert compared to normal COVID-19 patients. RESULTS: Among the total of 2,141 COVID-19 patients, 31 (1.45%) developed azvudine-induced liver injury, which is classified as an occasional adverse reaction. Liver injury was observed in 93.55% of patients between days 4 and 12 of the azvudine treatment, with elevated transaminases as the primary clinical manifestation. Univariate and binary logistic regression analyses indicated that low albumin levels and co-administration of low-molecular-weight heparin were statistically significant risk factors (p < 0.05). CONCLUSION: This study represents the first investigation of azvudine-induced liver injury and high-risk patients using the CHPS. The findings provide valuable insights to promote the safety of anti-COVID-19 drugs, serving as an important reference for future drug safety measures.


Subject(s)
Azides , COVID-19 , Chemical and Drug Induced Liver Injury, Chronic , Deoxycytidine/analogs & derivatives , Humans , Heparin, Low-Molecular-Weight/adverse effects , Pharmacovigilance , Retrospective Studies , Case-Control Studies , Chemical and Drug Induced Liver Injury, Chronic/drug therapy , Prospective Studies , Risk Factors , Albumins
16.
Biomed Pharmacother ; 174: 116485, 2024 May.
Article in English | MEDLINE | ID: mdl-38518602

ABSTRACT

BACKGROUND: Glucagon-like peptide-1 (GLP-1)/glucagon (GCG) dual receptor agonists with different receptor selectivity are under investigation and have shown significant improvement in both weight loss and glycemic control, but the optimal potency ratio between the two receptors to balance efficacy and safety remains unclear. EXPERIMENTAL APPROACH: We designed and constructed several dual receptor agonists with different receptor potency ratios using Fc fusion protein technology. The long-term effects of the candidates on body weight and metabolic dysfunction-associated steatotic liver disease (MASLD) were evaluated in diet-induced obese (DIO) model mice, high-fat diet (HFD)-ob/ob mice and AMLN diet-induced MASLD mice. Repeat dose toxicity assays were performed to investigate the safety profile of the candidate (HEC-C070) in Sprague Dawley (SD) rats. KEY RESULTS: The high GCG receptor (GCGR) selectivity of HEC-C046 makes it more prominent than other compounds for weight loss and most MASLD parameters but may lead to safety concerns. The weight change of HEC-C052 with the lowest GCG agonism was inferior to that of selective GLP-1 receptor agonist (GLP-1RA) semaglutide in DIO model mice. The GLP-1R selectivity of HEC-C070 with moderate GCG agonism has a significant effect on weight loss and liver function in obese mice, and its lowest observed adverse effect level (LOAEL) was 30 nmol/kg in the repeat dose toxicity study. CONCLUSION: We compared the potential of the Fc fusion protein GLP-1/GCG dual receptor agonists with different receptor selectivity to provide the setting for future GLP-1/GCG dual receptor agonists to treat obesity and MASLD.


Subject(s)
Diet, High-Fat , Glucagon-Like Peptide 1 , Glucagon-Like Peptide-1 Receptor , Immunoglobulin Fc Fragments , Obesity , Receptors, Glucagon , Recombinant Fusion Proteins , Animals , Humans , Mice , Rats , Diet, High-Fat/adverse effects , Glucagon-Like Peptide 1/agonists , Glucagon-Like Peptide-1 Receptor/agonists , Glucagon-Like Peptide-1 Receptor/metabolism , Glucagon-Like Peptides/pharmacology , Immunoglobulin Fc Fragments/pharmacology , Mice, Inbred C57BL , Mice, Obese , Obesity/drug therapy , Obesity/metabolism , Rats, Sprague-Dawley , Receptors, Glucagon/agonists , Receptors, Glucagon/metabolism , Recombinant Fusion Proteins/pharmacology , Weight Loss/drug effects
17.
Front Neurol ; 15: 1268433, 2024.
Article in English | MEDLINE | ID: mdl-38440116

ABSTRACT

Background and objective: Stent-assisted coil (SAC) embolization is a commonly used endovascular treatment for unruptured intracranial aneurysms (UIAs) but can be associated with symptomatic delayed intracerebral hemorrhage (DICH). Our study aimed to investigate the hemodynamic risk factors contributing to DICH following SAC embolization and to establish a classification for DICH predicated on hemodynamic profiles. Methods: This retrospective study included patients with UIAs located in the internal carotid artery (ICA) treated with SAC embolization at our institution from January 2021 to January 2022. We focused on eight patients who developed postoperative DICH and matched them with sixteen control patients without DICH. Using computational fluid dynamics, we evaluated the hemodynamic changes in distal arteries [terminal ICA, the anterior cerebral artery (ACA), and middle cerebral artery (MCA)] pre-and post-embolization. We distinguished DICH-related arteries from unrelated ones (ACA or MCA) and compared their hemodynamic alterations. An imbalance index, quantifying the differential in flow velocity changes between ACA and MCA post-embolization, was employed to gauge the flow distribution in distal arteries was used to assess distal arterial flow distribution. Results: We identified two types of DICH based on postoperative flow alterations. In type 1, there was a significant lower in the mean velocity increase rate of the DICH-related artery compared to the unrelated artery (-47.25 ± 3.88% vs. 42.85 ± 3.03%; p < 0.001), whereas, in type 2, there was a notable higher (110.58 ± 9.42% vs. 17.60 ± 4.69%; p < 0.001). Both DICH types demonstrated a higher imbalance index than the control group, suggesting an association between altered distal arterial blood flow distribution and DICH occurrence. Conclusion: DICH in SAC-treated UIAs can manifest as either a lower (type 1) or higher (type 2) in the rate of velocity in DICH-related arteries. An imbalance in distal arterial blood flow distribution appears to be a significant factor in DICH development.

18.
Front Cardiovasc Med ; 11: 1288659, 2024.
Article in English | MEDLINE | ID: mdl-38440210

ABSTRACT

Drug-eluting stents (DES) play a crucial role in treating coronary artery disease (CAD) by preventing restenosis. These stents are coated with drug carriers that release antiproliferative drugs within the vessel. Over the past two decades, DES have been employed in clinical practice using various materials, polymers, and drug types. Despite optimizations in their design and materials to enhance biocompatibility and antithrombotic properties, evaluating their long-term efficacy and safety necessitates improved clinical follow-up and monitoring. To delineate future research directions, this study employs a bibliometric analysis approach. We comprehensively surveyed two decades' worth of literature on DES for CAD using the Web of Science Core Collection (WOSCC). Out of 5,778 articles, we meticulously screened them based on predefined inclusion and exclusion criteria. Subsequently, we conducted an in-depth analysis encompassing annual publication trends, authorship affiliations, journal affiliations, keywords, and more. Employing tools such as Excel 2021, CiteSpace 6.2R3, VOSviewer 1.6.19, and Pajek 5.17, we harnessed bibliometric methods to derive insights from this corpus. Analysis of annual publication data indicates a recent stabilisation or even a downward trend in research output in this area. The United States emerged as the leading contributor, with Columbia University and CRF at the forefront in both publication output and citation impact. The most cited document pertained to standardized definitions for clinical endpoints in coronary stent trials. Our author analysis identifies Patrick W. Serruys as the most prolific contributor, underscoring a dynamic exchange of knowledge within the field.Moreover, the dual chart overlay illustrates a close interrelation between journals in the "Medicine," "Medical," and "Clinical" domains and those in "Health," "Nursing," and "Medicine." Frequently recurring keywords in this research landscape include DES coronary artery disease, percutaneous coronary intervention, implantation, and restenosis. This study presents a comprehensive panorama encompassing countries, research institutions, journals, keyword distributions, and contributions within the realm of DES therapy for CAD. By highlighting keywords exhibiting recent surges in frequency, we elucidate current research hotspots and frontiers, thereby furnishing novel insights to guide future researchers in this evolving field.

19.
Small ; : e2312281, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38456782

ABSTRACT

The low-toxic and environmentally friendly 2D lead-free perovskite has made significant progress in the exploration of "green" X-ray detectors. However, the gap in detection performance between them and their lead-based analogues remains a matter of concern that cannot be ignored. To reduce this gap, shortening the interlayer spacing to accelerate the migration and collection of X-ray carriers is a promising strategy. Herein, a Dion-Jacobson (DJ) lead-free double perovskite (4-AP)2 AgBiBr8 (1, 4-AP = 4-amidinopyridine) with an ultra-narrow interlayer spacing of 3.0 Å, is constructed by utilizing π-conjugated aromatic spacers. Strikingly, the subsequent enhanced carrier transport and increased crystal density lead to X-ray detectors based on bulk single crystals of 1 with a high sensitivity of 1117.3 µC Gy-1  cm-2 , superior to the vast majority of similar double perovskites. In particular, the tight connection of the inorganic layers by the divalent cations enhances structural rigidity and stability, further endowing 1 detector with ultralow dark current drift (3.06 × 10-8  nA cm-1  s-1  V-1 , 80 V), excellent multiple cycles switching X-ray irradiation stability, as well as long-term environmental stability (maintains over 94% photoresponse after 90 days). This work brings lead-free double perovskites one step closer to realizing efficient practical green applications.

20.
Patient Prefer Adherence ; 18: 709-720, 2024.
Article in English | MEDLINE | ID: mdl-38524198

ABSTRACT

Background: Colorectal, and gastric cancers have the second, and fourth mortality rates worldwide, respectively. Endoscopic screening is a crucial diagnostic tool for colorectal, and gastric cancers. Effective interventions can improve adherence to endoscopic screening in high-risk populations, which is important for cancer prevention and mortality reduction. This study aimed to identify interventions that could improve adherence to endoscopic screening for cancer in high-risk populations. Methods: Combination keywords including colorectal cancer, gastric cancer, screening adherence, and interventions were used to search for articles in PubMed, Web of Science, Cochrane Library, and MEDLINE Complete. The review methodology was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-SCR). Results: A total of 12 articles were included in this review: 9 randomized controlled trials(RCT) and 3 quasi-experimental studies(QEDs). Among the extracted studies, 11 were about colorectal cancer, and 1 was about gastric cancer. Most studies used lecture-based or Information Technology-based health education interventions. Narrative interventions have proven to be novel and effective approaches for promoting adherence to endoscopic screening. Health education interventions included cancer epidemiology, cancer risk factors, warning symptoms, and screening methods. Conclusion: All interventions involved were effective in increasing individual knowledge of cancer-related endoscopic screening, willingness to undergo screening, and screening behaviors. These findings provide a reference for designing endoscopy-related cancer screening interventions.

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