Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome characterized by systemic inflammation and immune dysregulation, in which macrophages play a key role in organ injury. This study aimed to investigate the role and mechanism of pyruvate dehydrogenase kinase 4 (PDK4) in ACLF to identify therapeutic targets that modulate macrophage function and mitigate ACLF progression.

Single-cell RNA sequencing data from healthy and ACLF liver tissues were analyzed from the Sequence Read Archive database. Transcriptomic data of peripheral blood mononuclear cells from ACLF patients (GSE168048) were also examined. In vitro experiments assessed PDK4 expression and macrophage polarization, and conditioned-medium studies evaluated effects on LO2 hepatocytes. In vivo validation was performed in ACLF mouse models treated with a PDK4 inhibitor.

Single-cell analysis revealed a predominance of M1-polarized hepatic macrophages in ACLF with marked upregulation of PDK4. Peripheral blood mononuclear cell transcriptomics showed that higher PDK4 expression correlated with 28-day mortality. In vitro, PDK4 expression increased in M1 macrophages; PDK4 inhibition attenuated M1 polarization and reduced cytotoxic effects on LO2 cells. In vivo, pharmacologic inhibition of PDK4 suppressed M1 polarization in macrophages, alleviated liver inflammation, and reduced tissue injury. Mechanistically, PDK4 promoted M1 polarization via activation of signal transducer and activator of transcription 1 signaling.

PDK4 is a key pro-inflammatory regulator in ACLF by promoting M1 macrophage polarization. Targeting PDK4 may be a promising strategy to attenuate inflammation and improve clinical outcomes in ACLF.

Fiberoptic bronchoscopy involves various topical airway anesthesia protocols, which can impact patient comfort, procedural ease, and overall outcomes. This study aimed to compare pre-procedure lignocaine spray (PPL) and spray-as-you-go (SAYG) airway anesthesia in terms of patient discomfort and operator comfort during fiberoptic bronchoscopy.

A single-blind randomized controlled trial was conducted at the Pulmonology Department of Shaikh Zayed Hospital, Lahore, Pakistan, from March 2021 to March 2022. Fifty participants were randomly assigned to two groups (n = 25 each). Standard procedural sedation with midazolam and 2 mL of 4% lignocaine spray in the oropharynx was used to suppress the gag reflex. Additionally, 2% lignocaine spray was administered during the procedure according to body weight (3 mg/kg) via oral scope insertion. Cough severity, pain perception, and operator comfort were assessed using the Visual Analogue Scale, Faces Pain Rating Scale, and a 4-point Likert scale, respectively.

Demographic characteristics were comparable between the groups, with a minor age difference (PPL: 53.25 years vs. SAYG: 50.88 years, p = 0.017). No significant differences were observed in pain perception, cough scores, or procedure duration between the PPL and SAYG groups. Operator comfort scores showed a trend favoring PPL (60% rated as “comfortable” or “very comfortable” vs. 28% in SAYG), though the difference was not statistically significant (p = 0.108).

Both PPL and SAYG topical airway anesthesia methods demonstrated similar effectiveness in pain control, cough suppression, operator comfort, and procedure duration. There was a slight, non-significant preference for PPL in operator comfort. These findings suggest that either technique may be effectively used, with potential implications for procedural efficiency and patient outcomes.

Cell cycle checkpoint-related genes (CCCRGs) are implicated in the development and progression of hepatocellular carcinoma (HCC). However, their precise roles and underlying mechanisms remain insufficiently characterized and require further investigation. This study aimed to explore the prognostic significance of CCCRGs in HCC, and to investigate the mechanism by which they promote the progression of HCC.

HCC datasets from The Cancer Genome Atlas and International Cancer Genome Consortium were analyzed to identify hub genes. A prognostic model was constructed and validated using Kaplan–Meier analysis, nomogram, calibration curves, decision curve analysis, and receiver operating characteristic analysis. Immune infiltration patterns were assessed using single sample gene set enrichment analysis, while pathway activities were evaluated via gene set variation analysis. Single-cell RNA sequencing data from GSE149614 were analyzed with Seurat and CellChat to investigate cell–cell communication. Patient-derived HCC specimens were examined through immunohistological evaluation, HCC cell lines were used for in vitro functional assays, and in vivo tumor growth was assessed through animal experiments.

CCCRGs showed significant associations with prognosis, malignant biological behavior, and immune responses in HCC. Centromere protein (CENP) I was identified as a critical hub gene that markedly promoted HCC proliferation, metastasis, and epithelial–mesenchymal transition, while inhibiting apoptosis. Mechanistically, CENPI suppressed YAP phosphorylation, enhancing its nuclear translocation and thereby driving malignant progression. Additionally, CENPI impaired immune effector cell infiltration, likely by disrupting tumor antigen presentation and chemokine-mediated CD8+ T cell chemotaxis, thereby promoting immune escape.

This study underscores the prognostic significance of CCCRGs in HCC and identifies CENPI as a key driver of tumor progression through the Hippo pathway. Furthermore, it reveals CENPI’s role in promoting immune escape, suggesting novel therapeutic targets for HCC treatment.

Candida species, particularly Candida albicans, are major contributors to denture-induced stomatitis because of their ability to form biofilms on removable dental prostheses. Although chemical cleansers are effective, concerns regarding material degradation and mucosal irritation have spurred interest in non-chemical alternatives. This review aims to systematically compare the efficacy of chemical and non-chemical denture cleansers in reducing Candida spp. on removable dental prostheses.

A systematic review was conducted according to the PRISMA 2020 guidelines. Comprehensive searches of PubMed, Scopus, and Web of Science (2003–2025) yielded 624 records. After duplicate removal and screening, 20 studies (10 randomized controlled trials (RCTs) and 10 in vitro studies) were included. The risk of bias was assessed using the Cochrane Risk of Bias 2.0 for RCTs and QUIN/SYRCLE tools for in vitro studies.

Chemical cleansers such as sodium hypochlorite (0.25–2.5%), chlorhexidine (0.2–2%), and effervescent peroxide tablets achieved 80–100% colony-forming unit reduction in most studies, with some reporting complete biofilm eradication. In contrast, non-chemical agents showed a 40–85% colony-forming unit reduction rate. Chemical cleansers caused increased surface roughness and discoloration in six of the ten studies included. Non-chemical agents preserved material integrity and were preferred by patients for their taste and ease of use. The risk of bias was low to moderate in 80% of the RCTs and low in 10 of the 13 in vitro studies.

Chemical denture cleansers are more potent antifungal agents, but they may damage prosthetic materials. Non-chemical cleansers offer safe and moderately effective alternatives to chemical cleansers. A personalized, evidence-based oral hygiene regimen is recommended for patients.

Clove essential oil (CEO) derived from Syzygium aromaticum and miswak (Salvadora persica) contains bioactive compounds with antimicrobial properties. Due to the growing interest in alternatives to conventional antibiotics, this study aimed to evaluate the in vitro antimicrobial efficacy of CEO, miswak, and their combination against key peri-implantitis pathogens.

The antimicrobial activities of CEO, miswak, and their combinations were tested against Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia. Disc diffusion and serial dilution methods were used to measure the inhibition zones and minimum inhibitory concentrations, respectively. Doxycycline served as a standard antibiotic for comparison, while ethanol was used as a negative control. Data were analyzed using one-way analysis of variance and Tukey’s honestly significant difference test, with significance set at α = 0.05.

CEO exhibited inhibition zones of 10–16 mm, comparable to that of doxycycline (13–16 mm), whereas miswak (6–13 mm vs. 1–14 mm) and the CEO–miswak combination (8–14 mm vs. 0–14 mm) showed lower activity. Mean minimum inhibitory concentration values were lowest for doxycycline (1.73 ± 0.46 µg/mL), followed by CEO (2.37 ± 0.24 µg/mL) and CEO–miswak combination (2.92 ± 0.12 µg/mL). Statistical analysis showed that the CEO–miswak combination was less effective than CEO (p = 0.0326) and doxycycline (p = 0.0001), but not different from miswak (p = 0.9836). CEO showed slightly greater activity than miswak (p = 0.0605).

Among the natural extracts tested, CEO exhibited superior antimicrobial efficacy, whereas miswak was less effective. The combination of CEO with miswak did not enhance antimicrobial efficacy, suggesting antagonistic interactions between their bioactive compounds.

In the past decade, immune checkpoint inhibitors (ICIs) have dramatically changed cancer treatment, significantly improving outcomes for patients with various malignancies. Nonetheless, their widespread application has resulted in a rise in immune-related adverse events due to excessive immune activation, including immune-mediated hepatotoxicity (IMH). IMH can cause serious complications and even death, underscoring the need for early prediction and intervention. This review outlines the current understanding of risk factors and predictive biomarkers for IMH in cancer patients undergoing ICI therapy, with risk factors divided into patient-associated, tumor-associated, and agent-associated categories. Higher IMH risk is related to female sex, younger age, extreme BMI, Asian ethnicity, and chronic liver disease. Cancer type, prior ICI treatment, dual ICI combination therapy, and the concurrent use of chemotherapy, targeted agents, or other hepatotoxic drugs (e.g., acetaminophen, statins) also increase the risk of IMH. Potential predictive biomarkers encompass circulating blood cells, serum proteins, autoantibodies, cytokines, gene profiles, and the gut microbiome. Despite promising findings, the predictive value of these biomarkers remains inconsistent, and no definitive biomarker has been established for routine clinical use. Large-scale prospective studies are essential to verify the predictive value of these biomarkers and facilitate their integration into clinical practice, thereby providing deeper insights into the early identification and individualized management of IMH during ICI therapy.

Peginterferon-α treatment exhibits low rates of the serological conversion rate of hepatitis B e antigen (HBeAg) and the negative conversion rate of hepatitis B virus (HBV) DNA, with significant myelosuppression leading to treatment discontinuation in some patients. Traditional Chinese medicine (TCM) may ameliorate liver inflammation and modulate immune responses. This study aims to investigate the efficacy of combining TCM with pegylated-interferon (PEG-IFN) α-2b and its impact on myelosuppression adverse effects.

This study included 117 HBeAg-positive chronic hepatitis B (CHB) patients who started initial antiviral therapy at Xiamen Hospital of TCM between June 2018 and January 2023. According to the treatment regimen, patients were divided into the observation group (n = 56, receiving PEG-IFN α-2b combined with Licorice 15 g, Angelica sinensis 20 g, Poria 20 g, Paeonia lactiflora 20 g, Rhizoma Atractylodis Macrocephalae 20 g, Radix Bupleurum Chinense 20 g, Mentha piperita 3 g, Ginger three slices for more than six months) and the control group (n = 61, receiving PEG-IFN α-2b alone). This study retrospectively analyzed etiological indicators, liver biochemical indicators, and blood routine tests before and after treatment.

After 24 and 48 weeks of treatment, the observation group demonstrated significantly superior outcomes to the control group in quantitative reduction of hepatitis B surface antigen, the serological conversion rate of HBeAg, and the reduction in HBV DNA quantification (P < 0.05). By week 48, the HBV DNA negative conversion rate in the observation group (46.67%) was significantly higher than that in the control group (26.67%) (P < 0.05). Regarding safety, the incidence of myelosuppression in the observation group was significantly lower than that in the control group at both 24 and 48 weeks of treatment (P < 0.05)

Real-world findings demonstrate that adjunctive TCM significantly enhances the antiviral efficacy of peginterferon α-2b in HBeAg-positive CHB patients while concurrently mitigating treatment-limiting myelosuppression. This combination strategy may represent a clinically valuable approach to optimizing interferon-based therapy for CHB.

Super-enhancers (SEs) are highly enriched clusters of transcriptional regulatory elements within the genome, occupying a central position in tumorigenesis and development. This review aims to synthesize the rapidly expanding body of knowledge on SEs as the central hub of tumor transcriptional regulation.SEs integrate specific transcription factors, dynamic epigenetic modifications (such as H3K27ac), and restructure the three-dimensional spatial architecture of the genome to aberrantly drive the expression of proto-oncogenes and cell identity-related genes. This activity sustains the malignant phenotype, stem cell properties, metabolic reprogramming, and therapy resistance of tumor cells. Their functions involve emerging physical mechanisms such as phase separation forming transcriptional condensates and long-range chromatin looping. The activity of SEs exhibits high tumor-type and tissue specificity. They are activated through unique mechanisms in different cancers, becoming key nodes of “transcriptional addiction” in tumor cells. This characteristic also makes them highly promising therapeutic targets. Inhibitors targeting core SE components (such as the BET protein BRD4 and transcriptional kinases CDK7/9), epigenetic drugs, and strategies aimed at disrupting their phase-separated condensates have shown selective efficacy in various preclinical tumor models. In conclusion, SEs serve as pivotal hubs of transcriptional addiction in cancer by integrating diverse molecular mechanisms to drive oncogenic programs, and their specific components present promising therapeutic targets; future advances in multi-omics and precision strategies will be key to translating these findings into clinical applications.

Empirical and theoretical studies can be distinguished among the areas of investigation of the renin-angiotensin-aldosterone system (RAAS) and its relationship with the development of cardiovascular diseases. Theoretical work is based mainly on the bioinformatic analysis of key elements of RAAS (genes, proteins, metabolites), on calculations and predictions of protein interactions, and on mechanisms of RAAS gene expression regulation. An associative gene network based on big data analysis allows us to reveal relationships among the proteins, regulatory pathways, and biological processes acting in RAAS, as well as to identify new diagnostic markers, therapeutic targets, putative molecular mechanisms of the development of RAAS-associated diseases, drug interactions, and drug toxicity.

The reconstruction and analysis of associative gene networks were performed using ANDSystem. The regulation of RAAS-associated gene expression was analyzed by transcription factor (TF) binding sites (TFBSs) prediction in the proximal promoters of these genes and by studying interactions between TFs themselves using the Ensembl Biomart web service and AnimalTFDB 4.0. The recognition of potential TFBSs in RAAS gene promoters was performed using MoLoTool.

According to the centrality criteria of the RAAS associative gene network, the following proteins were identified as exerting a significant influence on information interplay between network components: IL6, EDN1, TNFA, MK01, LEP, and JUN. Analysis of the ten identified TFs and their TFBSs among the genes in the RAAS network under study revealed clusters of three to 26 genes regulated by them.

Components with the highest values of centrality and vertex degrees were identified in the reconstructed associative gene network of the RAAS, and ten TFs supposed to regulate 26 RAAS genes were determined.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and chronic kidney disease (CKD) have shown a significant increase in comorbidity on a global scale due to the prevalence of metabolic syndrome. In 2023, a number of academic societies formally proposed the concept of MASLD, superseding the previous terminology of “non-alcoholic fatty liver disease” and “metabolic dysfunction-associated fatty liver disease”. The diagnostic criteria have been revised to place greater emphasis on the association between hepatic steatosis and cardiometabolic risk factors. MASLD constitutes an independent risk factor for CKD, with this risk potentially increasing in line with the severity of fatty degeneration and the progression of hepatic fibrosis. CKD may represent a potential risk factor for the progression of fibrosis in patients with MASLD. The interaction between the two conditions may accelerate the occurrence of cardiovascular events and increase the risk of all-cause mortality. MASLD and CKD may share core pathophysiological mechanisms, including genetic variants, insulin resistance, lipid metabolism disorders, chronic inflammation, oxidative stress, and gut microbiota dysbiosis. However, the bidirectional causal relationship between the two conditions and the molecular dialogue between organs remains unclear. Furthermore, there are significant gaps in clinical prediction tools and targeted treatment strategies for comorbidities. This paper reviews common pathophysiological mechanisms in MASLD and CKD, the epidemiological and clinical evidence linking MASLD to the risk of CKD, biomarkers and clinical prediction models for coexisting conditions, and potential therapeutic strategies. Our aim is to provide a theoretical basis for early identification, mechanism exploration, and clinical treatment of comorbidities.