Efficacy Of Treatment Research Articles

Proton Therapy in Uveal Melanoma

Background/Objectives: Uveal melanoma is the most common primary intraocular malignancy in adults. Treatment options for localized, early-stage disease include enucleation, brachytherapy, and proton beam therapy. This review aims to evaluate the role of proton therapy in the definitive management of uveal melanoma, focusing on its physics, radiobiology, treatment techniques, and associated outcomes. Methods: This narrative review synthesizes current literature on proton therapy for uveal melanoma, emphasizing case selection, treatment efficacy, and side effects. Results: Proton therapy offers significant advantages for thicker uveal melanomas (over 8 mm) due to its unique physical properties, including a rapid dose fall-off that protects critical structures like the retina and optic nerve. Proton therapy may have benefits in tumor control for ocular melanomas given its increased relative biological effectiveness relative to photon therapy for these typically more radioresistant melanomas. Proton therapy may also hold special value for uveal melanomas in close proximity to the optic nerve, as patients are at high risk of visual toxicities with brachytherapy. The review discusses the efficacy of proton therapy across small, medium, and large tumors, along with strategies for improving patient survival through combined systemic therapy. Additionally, the potential of ocular reirradiation with proton therapy is addressed. Conclusions: Proton therapy is an effective treatment for uveal melanoma. It offers advantages over brachytherapy for large tumors, tumors that are close to the optic nerve or insertion of extra-ocular muscles.

Sustained hair regrowth with continued ritlecitinib treatment through Week 48 in patients with alopecia areata with or without early target responses: post hoc analysis of the ALLEGRO phase 2b/3 trial

Few treatments for alopecia areata (AA) have demonstrated sustained efficacy. Evaluate the efficacy and safety of continued ritlecitinib treatment to Week 48 in patients with AA with or without target efficacy responses at Week 24. Patients aged ≥12 years received daily ritlecitinib (± 4-week loading dose): 200/50 mg, 200/30 mg, 50 mg, or 30 mg. Patients with clinical response at Week 24, based on a Severity of Alopecia Tool (SALT) score ≤20 and ≤10 were evaluated for sustained response through Week 48. Nonresponders at Week 24 were assessed for response through Week 48. Among ritlecitinib-treated patients with SALT score ≤20 and ≤10 responses at Week 24, ≥85% and ≥68%, respectively, sustained these responses through Week 48. Of those with SALT score >20 at Week 24, 22%-34% achieved SALT score ≤20 at Week 48. Of those with a SALT score >10 at Week 24, 20%-26% achieved SALT score ≤10 at Week 48. Safety was similar across subgroups. Small sample size. Hair regrowth was sustained through Week 48 in patients with response at Week 24. Up to one-third of patients who did not meet target efficacy at Week 24 achieved response with continued ritlecitinib treatment.

Long-term efficacy of drug-coated balloon-based treatment for de novo left anterior descending artery disease

Drug-coated balloons (DCB) are increasingly utilized in percutaneous coronary intervention (PCI), but their effectiveness in coronary artery disease (CAD) needs further exploration. This study investigates the efficacy and safety of a DCB-based strategy for de novo left anterior descending artery (LAD) disease. Patients with de novo LAD lesions treated with DCB alone or combined with drug-eluting stents (DES) and were retrospectively enrolled from 2010 to 2023 (n = 268). The comparator group consisted of patients treated with second-generation DES from a Korean multicenter registry (n = 4,147). The primary endpoint was three-year major adverse cardiovascular events (MACE), including cardiac death, myocardial infarction, target vessel revascularization, target lesion thrombosis, and major bleeding. In the DCB-based group (n = 268), 218 (81.3%) received DCB-only, while 50 (18.7%) underwent a hybrid approach. After propensity score-matching of 243 paired subjects, baseline characteristics were balanced. The DCB-based PCI reduced overall stent burden by 86.7% and significantly lowered the risk of MACE at three years compared to DES-only PCI (4.5% vs. 7.6%, HR 0.50, 95% CI 0.28–0.90; p = 0.020). The most significant reduction was in major bleeding. The DCB-based approach offers an alternative to DES-only strategy for LAD PCI by reducing three-year MACE risk, supporting its use in treating de novo CAD.

Alpha-hemolysin promotes internalization of Staphylococcus aureus into human lung epithelial cells via caveolin-1- and cholesterol-rich lipid rafts

Staphylococcus aureus is a pathogen associated with severe respiratory infections. The ability of S. aureus to internalize into lung epithelial cells complicates the treatment of respiratory infections caused by this bacterium. In the intracellular environment, S. aureus can avoid elimination by the immune system and the action of circulating antibiotics. Consequently, interfering with S. aureus internalization may represent a promising adjunctive therapeutic strategy to enhance the efficacy of conventional treatments. Here, we investigated the host-pathogen molecular interactions involved in S. aureus internalization into human lung epithelial cells. Lipid raft-mediated endocytosis was identified as the main entry mechanism. Thus, bacterial internalization was significantly reduced after the disruption of lipid rafts with methyl-β-cyclodextrin. Confocal microscopy confirmed the colocalization of S. aureus with lipid raft markers such as ganglioside GM1 and caveolin-1. Adhesion of S. aureus to α5β1 integrin on lung epithelial cells via fibronectin-binding proteins (FnBPs) was a prerequisite for bacterial internalization. A mutant S. aureus strain deficient in the expression of alpha-hemolysin (Hla) was significantly impaired in its capacity to enter lung epithelial cells despite retaining its capacity to adhere. This suggests a direct involvement of Hla in the bacterial internalization process. Among the receptors for Hla located in lipid rafts, caveolin-1 was essential for S. aureus internalization, whereas ADAM10 was dispensable for this process. In conclusion, this study supports a significant role of lipid rafts in S. aureus internalization into human lung epithelial cells and highlights the interaction between bacterial Hla and host caveolin-1 as crucial for the internalization process.

Innovative Use of Nanomaterials in Treating Retinopathy of Prematurity

Background/Objectives: Retinopathy of prematurity (ROP) is a severe condition primarily affecting premature infants with a gestational age (GA) of 30 weeks or less and a birth weight (BW) of 1500 g or less. The objective of this review is to examine the risk factors, pathogenesis, and current treatments for ROP, such as cryotherapy, laser photocoagulation, and anti-VEGF therapy, while exploring the limitations of these approaches. Additionally, this review evaluates emerging nanotherapeutic strategies to address these challenges, aiming to improve ROP management. Methods: A comprehensive literature review was conducted to gather data on the pathogenesis, traditional treatment methods, and novel nanotherapeutic approaches for ROP. This included assessing the efficacy and safety profiles of cryotherapy, laser treatment, anti-VEGF therapy, and nanotherapies currently under investigation. Results: Traditional treatments, while effective in reducing disease progression, exhibit limitations, including long-term complications, tissue damage, and systemic side effects. Nanotherapeutic approaches, on the other hand, have shown potential in offering targeted drug delivery with reduced systemic toxicity, improved ocular drug penetration, and sustained release, which could decrease the frequency of treatments and enhance therapeutic outcomes. Conclusions: Nanotherapies represent a promising advancement in ROP treatment, offering safer and more effective management strategies. These innovations could address the limitations of traditional therapies, reducing complications and improving outcomes for premature infants affected by ROP. Further research is needed to confirm their efficacy and safety in clinical practice.

Efficacy of Atmospheric Pressure Plasma Jet-Induced Surface Treatment on Wettability, Surface Topography, and Shear Bond Strength of Ceramic Surfaces for CAD-On Assembly

Efficacy of Atmospheric Pressure Plasma Jet-Induced Surface Treatment on Wettability, Surface Topography, and Shear Bond Strength of Ceramic Surfaces for CAD-On Assembly

Efficacy of Nonpharmacological Treatment in Children and Adolescent with Tic Disorder: A Systematic Review

Efficacy of Nonpharmacological Treatment in Children and Adolescent with Tic Disorder: A Systematic Review

Current progress on the microbial therapies for acute liver failure

Acute liver failure (ALF), associated with a clinical fatality rate exceeding 80%, is characterized by severe liver damage resulting from various factors in the absence of pre-existing liver disease. The role of microbiota in the progression of diverse liver diseases, including ALF, has been increasingly recognized, with the interactions between the microbiota and the host significantly influencing both disease onset and progression. Despite growing interest in the microbiological aspects of ALF, comprehensive reviews remain limited. This review critically examines the mechanisms and efficacy of microbiota-based treatments for ALF, focusing on their role in prevention, treatment, and prognosis over the past decade.

Matrine alkaloids modulating DNA damage repair in chemoresistant non-small cell lung cancer cells

BackgroundNon-small cell lung cancer (NSCLC) presents a significant challenge in the medical field due to its high incidence and resistance to chemotherapy. Chemoresistance in NSCLC diminishes treatment efficacy and contributes to poor patient outcomes. Matrine alkaloids have shown promise in reversing chemotherapy resistance in NSCLC by targeting DNA repair mechanisms.MethodsUtilizing molecular dynamics simulations, we explored the interactions between Matrine alkaloids and DNA repair-related proteins to elucidate their impact on NSCLC cells. In vitro experiments involved treating A549/DDP cells with Matrine alkaloids to evaluate their sensitizing effects on lung cancer cells. Additionally, animal model experiments were conducted to validate the therapeutic potential of Matrine alkaloids in NSCLC treatment.ResultsOur findings demonstrate that Matrine alkaloids disrupt DNA damage repair processes in NSCLC cells, leading to increased sensitivity to chemotherapy. Molecular docking studies revealed the intricate mechanisms by which Matrine alkaloids interact with DNA repair proteins, impacting cell survival and proliferation. Both cell experiments and animal models confirmed the chemosensitizing effects of Matrine alkaloids in NSCLC treatment.ConclusionMatrine alkaloids offer a promising avenue for overcoming chemotherapy resistance in NSCLC by interfering with DNA repair pathways. This study lays a solid foundation for future clinical investigations into the potential of Matrine alkaloids as effective therapeutic agents for enhancing NSCLC treatment outcomes.

Department-specific patterns of bacterial communities and antibiotic resistance in hospital indoor environments

The hospital indoor environment has a crucial impact on the microbial exposures that humans encounter. Resistance to antibiotics is a mechanism used by bacteria to develop resilience in indoor environments, and the widespread use of antibiotics has led to changes in the ecological function of resistance genes and their acquisition by pathogens. By integrating the 16S rRNA Illumina sequencing and high-throughput-quantitative PCR approaches with water and air dust samples across seven departments in Peking University Shenzhen Hospital, China, this study yields intriguing findings regarding the department-specific variations, correlations and source tracing of bacteria, antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) within the hospital indoor environment. A notable observation was the pivotal role played by seasonal variations in shaping the bacterial composition across the entire hospital indoor environment. Another department-specific finding was the correlation between ARGs and MGEs abundance, which was evident in the overall hospital indoor environment, but not found in the blood test room, ophthalmology, and gynecology departments. Notably, as an important source of bacteria and ARGs/MGEs for the blood test room, the gynecology department also presented a close link between bacterial communities and the presence of ARGs/MGEs. Additionally, the results reiterate the importance of surveillance and monitoring of antibiotic resistance, specifically in Legionella spp. in man-made water systems, and highlight the significance of understanding genetic elements like Tp614 involved in gene transfer and recombination, and their impact on antimicrobial treatment efficacy. Key points•The department-specific variations, correlations and source tracing of bacteria, ARGs, and MGEs were uncovered in the hospital’s indoor environment.•Although each department exhibited consistent seasonal impacts on bacterial compositions, the co-occurrence between the presence of ARGs and MGEs was exclusively evident in the emergency, surgery, pneumology and otolaryngology departments.•The gynecology department emerged as a crucial source of bacteria, ARGs and MGEs within the hospital. Additionally, it was found to exhibit a significant correlation between bacterial communities and the presence of ARGs and MGEs.

Correlations among quality of life, spinal mobility, and disease activity in early-treated axial spondyloarthritis: a single-center cross-sectional study

BackgroundAxial spondyloarthritis (axSpA) significantly impacts patients’ lives. The ASAS-OMERACT guideline was formulated for the multidimensional evaluation of axSpA patients, employing a specific set of tools. Given the pivotal role of patient perception, comprehensive correlation among these tools, especially concerning quality of life, may provide a clinically relevant perspective and enhance treatment efficacy in the early stages of the disease. This study aims to investigate the correlation among disease activity, functional ability, and quality of life in early-treated axSpA patients. In addition, the association between high disease activity and clinical characteristics was explored.MethodsThis cross-sectional study was conducted in a tertiary hospital in Thailand. Patients diagnosed with axSpA according to ASAS classification criteria and receiving treatment from rheumatologists within three years of onset of symptoms were included. Clinical and laboratory data were retrieved from a hospital database. Disease activity was assessed using the Ankylosing Spondylitis Disease Activity Score with ESR or CRP (ASDAS-ESR/CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Spinal mobility was measured using the Bath Ankylosing Spondylitis Metrology Index (BASMI), while quality of life and function were evaluated using the ASAS Health Index (ASAS-HI) and Bath Ankylosing Spondylitis Functional Index (BASFI), respectively. The correlation between these measurements was analyzed using the Pearson correlation coefficient (r). Additionally, factors associated with high disease activity (ASDAS/CRP > 2.1) were explored using multivariate regression analysis.ResultsSixty-six patients (41 males; mean age 49.3 ± 13.3 years) were enrolled between April to December 2022. Disease activity (ASDAS-CRP) was significantly inversely correlated with spinal mobility (BASMI), function (BASFI), and quality of life (ASAS-HI). High disease activity was associated with obesity (BMI ≥ 30 kg/m^2) and a longer duration of symptoms before treatment (≥ 2 years).ConclusionIn early-treated axSpA patients, ASDAS-CRP showed significant correlations with functional ability, quality of life, and spinal mobility. High disease activity was associated with obesity and a longer pre-treatment symptom duration in our study. Early treatment may enhance patients’ function, mobility, and quality of life, with weight reduction being possibly beneficial for obese axSpA patients.Clinical trial numberNot applicable.

Budget impact analysis of TPMT and NUDT15 pharmacogenomic testing for 6-mercaptopurine in pediatric acute lymphoblastic leukemia patients

Background Pharmacogenomic testing identifies gene polymorphisms impacting drug metabolism, aiding in optimizing treatment efficacy and minimizing toxicity, thus potentially reducing healthcare utilization. 6-Mercaptopurine metabolism is affected by thiopurine methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15) polymorphisms. We sought to estimate the budget impact of preemptive pharmacogenomic testing for these genes in pediatric acute lymphoblastic leukemia (ALL) patients from an institutional perspective. Methods A Markov model was constructed to model the first cycle of the maintenance phase of chemotherapy for pediatric ALL patients transitioning between one of three health states: stable, moderately myelosuppressed, and severely myelosuppressed over 16 weeks, with each health state’s associated costs derived from the literature. The patient’s likelihood to experience moderate or severe myelosuppression based on metabolism phenotype was calculated from the literature and applied on a weekly basis, and the marginal budget impact of preemptive pharmacogenomic testing vs. no pharmacogenomic testing was calculated. One-way sensitivity analysis was conducted to assess parameter influence on results. Results Preemptive pharmacogenomic testing of TPMT and NUDT15 provided savings of up to $26 028 per patient during the maintenance phase. In the sensitivity analysis, the cost of outpatient management of moderate myelosuppression had the greatest impact on the budget, resulting in cost savings ranging from $8592 to $30 129 when the minimum and maximum costs of management were used in the model. Conclusion Preemptive pharmacogenomic testing for TPMT and NUDT15 polymorphisms before initiation of maintenance therapy for pediatric ALL patients yielded considerable cost savings.

Artificial Intelligence and Advanced Technology in Glaucoma: A Review

Background: Glaucoma is a leading cause of irreversible blindness worldwide, necessitating precise management strategies tailored to individual patient characteristics. Artificial intelligence (AI) holds promise in revolutionizing the approach to glaucoma care by providing personalized interventions. Aim: This review explores the current landscape of AI applications in the personalized management of glaucoma patients, highlighting advancements, challenges, and future directions. Methods: A systematic search of electronic databases, including PubMed, Scopus, and Web of Science, was conducted to identify relevant studies published up to 2024. Studies exploring the use of AI techniques in personalized management strategies for glaucoma patients were included. Results: The review identified diverse AI applications in glaucoma management, ranging from early detection and diagnosis to treatment optimization and prognosis prediction. Machine learning algorithms, particularly deep learning models, demonstrated high accuracy in diagnosing glaucoma from various imaging modalities such as optical coherence tomography (OCT) and visual field tests. AI-driven risk stratification tools facilitated personalized treatment decisions by integrating patient-specific data with predictive analytics, enhancing therapeutic outcomes while minimizing adverse effects. Moreover, AI-based teleophthalmology platforms enabled remote monitoring and timely intervention, improving patient access to specialized care. Conclusions: Integrating AI technologies in the personalized management of glaucoma patients holds immense potential for optimizing clinical decision-making, enhancing treatment efficacy, and mitigating disease progression. However, challenges such as data heterogeneity, model interpretability, and regulatory concerns warrant further investigation. Future research should focus on refining AI algorithms, validating their clinical utility through large-scale prospective studies, and ensuring seamless integration into routine clinical practice to realize the full benefits of personalized glaucoma care.

Genetic Profiling in Chronic Lymphocytic Leukemia: The Role of TP53 Mutations and IGHV Status in Treatment Decision-Making – A Case Report

Introduction. The TP53 gene encodes the p53 protein, crucial for DNA damage response, apoptosis, and cell cycle regulation. In chronic lymphocytic leukemia (CLL), TP53 loss due to 17p deletion or mutation leads to poor chemoimmunotherapy response and shorter survival. Patients with unmutated immunoglobulin heavy chain variable (IGHV) status exhibit a more aggressive disease course, poorer outcomes, and reduced response to standard chemoimmunotherapy. These genetic variations significantly affect disease progression, treatment choice, and response to therapy. Case Report. In November 2023, a 61-year-old man presented to our clinic with complaints of generalized weakness and rapid fatigue since October 2023. CLL was diagnosed in 2018 through pathohistological and immunohistochemical analysis of the bone marrow. The patient received no therapy until 2023 due to the absence of active disease signs. From March 28, 2023, to July 25, 2023, the patient received chemoimmunotherapy with the bendamustine and rituximab (BR) regimen. Five courses of therapy were administered; however, further treatment was discontinued due to side effects that occurred during the fifth course of bendamustine administration. A subsequent diagnostic evaluation aimed at assessing treatment efficacy, prognosis, and genetic profiling included a cytomorphological analysis, which revealed that lymphocytes comprised 80% of the cellular composition. Immunocytological analysis confirmed the presence of monoclonal atypical lymphocytes, accounting for 70% of the cell population. Next-generation sequencing identified a pathogenic TP53 mutation, and fragment analysis confirmed an unmutated IGHV status. The presence of the TP53 mutation and unmutated IGHV status categorizes the patient as being in the very high-risk group, for which the use of Bruton’s tyrosine kinase inhibitors (BTKIs) and/or B-cell lymphoma-2 (BCL-2) inhibitors is recommended. Conclusions. This case highlights the significance of comprehensive genetic profiling in CLL patients using techniques such as fluorescence in situ hybridization, polymerase chain reaction, and next-generation sequencing. Such profiling detects molecular genetic alterations, facilitating personalized and effective treatment.

Strategic Integration: A Cross-Disciplinary Review of the fNIRS-EEG Dual-Modality Imaging System for Delivering Multimodal Neuroimaging to Applications

Background: Recent years have seen a surge of interest in dual-modality imaging systems that integrate functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG) to probe brain function. This review aims to explore the advancements and clinical applications of this technology, emphasizing the synergistic integration of fNIRS and EEG. Methods: The review begins with a detailed examination of the fundamental principles and distinctive features of fNIRS and EEG techniques. It includes critical technical specifications, data-processing methodologies, and analysis techniques, alongside an exhaustive evaluation of 30 seminal studies that highlight the strengths and weaknesses of the fNIRS-EEG bimodal system. Results: The paper presents multiple case studies across various clinical domains—such as attention-deficit hyperactivity disorder, infantile spasms, depth of anesthesia, intelligence quotient estimation, and epilepsy—demonstrating the fNIRS-EEG system’s potential in uncovering disease mechanisms, evaluating treatment efficacy, and providing precise diagnostic options. Noteworthy research findings and pivotal breakthroughs further reinforce the developmental trajectory of this interdisciplinary field. Conclusions: The review addresses challenges and anticipates future directions for the fNIRS-EEG dual-modal imaging system, including improvements in hardware and software, enhanced system performance, cost reduction, real-time monitoring capabilities, and broader clinical applications. It offers researchers a comprehensive understanding of the field, highlighting the potential applications of fNIRS-EEG systems in neuroscience and clinical medicine.

Lessons learned from 12 years using the Woven Endobridge for the treatment of cerebral aneurysms in a multi-center series

Intrasaccular flow disruption with the Woven Endobridge (WEB) has become a well-established endovascular technique for the treatment of intracranial aneurysms. This study presents our 12-year experience with the WEB and evaluates its evolving indications, procedures, and outcomes. A consecutive series of 324 aneurysms treated with WEB between 2011 and 2023 at three neurovascular centers was retrospectively analyzed and the study group was divided into four treatment periods. Uni- and multivariate analyses were performed to evaluate factors associated with technical success, thromboembolic complications, and angiographic outcome. The mean aneurysm size was 7.0 ± 3.6 mm and decreased during the study period, while the proportion of atypical sites for WEB implantation increased. WEB implantation was technically successful in 96.0%, and the ratio of WEB width to dome width increased during the study period, indicating oversizing. The neurological complication rate was 4.9% (1.5% major, 3.4% minor) and the mid-term complete occlusion rate was 60.6% (81.9% adequate occlusion), with no statistical differences in either outcome measure between the study periods. In multivariate analyses, the use of WEB 17 was associated with increased technical success (HR: 7.4, 95%CI: 2.4-23.6, p<0.01), whereas ruptured aneurysm status (HR: 2.5, 95%CI: 1.0-6.0, p=0.04) and the use of additional stents (HR: 4.8, 95%CI: 1.6-14.4, p<0.01) predicted thromboembolic complications. Appropriate oversizing of the WEB favored mid-term complete occlusion (HR: 10.5, 95%CI: 1.3-83.3, p=0.03). The results suggest an expansion of the indications for WEB implantation and highlight the importance of oversizing for treatment efficacy.

Targeting Ferroptosis: Small-molecule Inducers as Novel Anticancer Agents.

Ferroptosis, a distinct form of regulated cell death characterized by iron-dependent lipid peroxidation and reactive oxygen species (ROS) accumulation, is increasingly recognized for its role in cancer development and as a potential therapeutic target. This review consolidates insights into the molecular mechanisms underpinning ferroptosis and evaluates the therapeutic potential of small-molecule inducers, such as erastin, RSL3, sulfasalazine, and sorafenib, which selectively trigger ferroptosis in cancer cells. It highlights the distinct morphological and molecular signatures of ferroptosis, its complex interplay with iron, lipid, and amino acid metabolic pathways, and the resultant implications for cancer treatment strategies. Strategic manipulation of the ferroptosis pathway offers a groundbreaking approach to cancer treatment, potentially circumventing the resistance that cancers develop against traditional apoptosis-inducing agents. Furthermore, it also emphasizes the necessity of refining these small molecules for clinical application and exploring their synergistic potential when combined with current therapies to augment overall treatment efficacy and improve patient outcomes. Ferroptosis thus emerges as a promising avenue in the realm of cancer therapy. Moving forward, research endeavors should focus on a more nuanced understanding of the interconnections between ferroptosis and other cell death modalities. Additionally, comprehensive evaluations of the long-term safety and therapeutic indices of the involved compounds are imperative. Such investigations are poised to herald a transformative shift in the paradigm of oncology, paving the way for innovative and targeted interventions.

Analysis of the Efficacy and Prospects for Application of Olorparib and Dabrafenib in Liver Cancer Treatment

Abstract Introduction/Objective To evaluate the effectiveness of Olaparib and Dabrafenib in the treatment of liver cancer and explore their potential prospects for future applications. Methods/Case Report A comprehensive analysis of relevant literature on Olaparib and Dabrafenib in the treatment of liver cancer was conducted, including clinical trials, case studies, and previous meta-analyses. Key indicators such as treatment efficacy, adverse reactions, and patient survival rates were examined. Results (if a Case Study enter NA) In patients treated with the two drugs, the proportion of AFP decreased was 60.24% and 65.87%, the proportion of serum ferritin decreased was 50.25% and 53.39%, the proportion of CT tumor abbreviations was 52.13% and 58.89%, and the effective rate was 38.14% and 40.02%, respectively. There was no significant difference between the two drugs (P &amp;gt; 0.05). Survival analysis showed that the median progression-free survival was 10.7 and 12.3 months, respectively, and the median overall survival was 17.6 and 20.1 months, respectively. The incidence of adverse events including fever, fatigue, chills, nausea and rash was 23.14% and 28.56%, respectively, and there was no significant difference between the two drugs (P &amp;gt; 0.05). Conclusion Olaparib and Dabrafenib demonstrate significant efficacy in the treatment of liver cancer, offering new therapeutic options for patients. The application prospects of these drugs are promising, and they are expected to become crucial components in liver cancer treatment. Further research and clinical practice will contribute to a more comprehensive understanding of their mechanisms of action, optimization of treatment regimens, and improvement of the overall quality of life for liver cancer patients.

Management of inflammaging in kidney diseases: focusing on the current investigational drugs.

To improve kidney disease treatments, it is crucial to understand how inflammaging affects patients´ longevity. We could potentially slow down kidney disease progression and enhance longevity by targeting specific pathways involved in inflammaging with potential drugs. This review offers an updated overview of 'anti-inflammaging' drugs currently in the kidney disease research pipeline, as well as those with potential for future therapeutic use. Furthermore, these drugs are categorized according to their mechanisms, including targeting inflammation, immune and metabolic regulation, oxidative stress, senescence, and autophagy, as demonstrated in preclinical and early clinical trials. Additionally, the review provides insights into key challenges and opinions for future advancements in this field. We reviewed recent advancements in applying different therapies to mitigate inflammaging in kidney diseases. We underscore the need for continued research to elucidate the complex pathways underlying inflammaging, which will be essential for the development of more precise and effective treatments. As research in this field advances, several emerging drugs appear promising for future investigation. While current findings are encouraging, further clinical studies are required to validate the therapeutic potential of these agents in kidney diseases, ultimately paving the way for more targeted and efficacious interventions.

A single dose of glycogen phosphorylase inhibitor improves cognitive functions of aged mice and affects the concentrations of metabolites in the brain

Inhibition of glycogen phosphorylase (Pyg) – a regulatory enzyme of glycogen phosphorolysis – influences memory formation in rodents. We have previously shown that 2-week intraperitoneal administration of a Pyg inhibitor BAY U6751 stimulated the “rejuvenation” of the hippocampal proteome and dendritic spines morphology and improved cognitive skills of old mice. Given the tedious nature of daily intraperitoneal drug administration, in this study we investigated whether a single dose of BAY U6751 could induce enduring behavioral effects. Obtained results support the efficacy of such treatment in significantly improving the cognitive performance of 20-22-month-old mice. Metabolomic analysis of alterations observed in the hippocampus, cerebellum, and cortex reveal that the inhibition of glycogen phosphorolysis impacts not only glucose metabolism but also various other metabolic processes.