Fine needle aspiration cytology (FNAC) is a cost-efficient technique for the management of thyroid nodules. Changes in the World Health Organization classification of thyroid tumors can influence reliability of cytology. The 2023 Bethesda System for Reporting Thyroid Cytopathology has adapted cytological nomenclature to these changes. The aim of this paper was to analyze the management of atypia of undetermined significance (AUS) in our institution.

Retrospective review of thyroid FNAC diagnosed with AUS in a single hospital between 2014 and 2022. We analyzed the management of patients and the risk of malignancy associated with AUS.

AUS represented 7.5% of all thyroid FNAC diagnoses (273 patients). In 74.1% of the patients, FNAC was repeated, and 54.9% of the lesions were downgraded. Surgical resection of the nodule was performed in 38.2% of the patients, mostly after a repeat FNAC with upgrading. Ninety-one percent of the patients downgraded in the repeat FNAC did not undergo surgery. The risk of malignancy of the AUS category after repeat FNAC was 26.1%. AUS diagnosis was due to nuclear atypia in 32% of the patients, and we found a significant association between nuclear atypia and upgrading in repeat FNAC. Of the 96 patients who underwent surgery in our series, 42 had malignant lesions, including noninvasive follicular thyroid neoplasms with papillary-like features.

The clinical management of AUS patients includes repeat FNAC, which is strongly correlated with the risk of malignancy. Nuclear atypia seems to be more predictive of malignancy than architectural patterns.

Obesity has become a global epidemic affecting diverse populations and leading to metabolic syndrome across different sexes and age groups. A significant aspect of obesity is the development of leptin resistance, primarily due to the inefficient transport of leptin across the blood-brain barrier and other mechanisms such as protein folding and dysregulation of leptin signaling in brain areas related to energy and adipose tissue metabolism. This hindrance in leptin delivery poses a challenge to using this adipokine as a potential therapy for obesity. Current research focuses on understanding the complex molecular pathways that link diet-induced obesity, characterized by increased levels of leptin, to the onset of metabolic syndrome. This syndrome encompasses various health issues, including type 2 diabetes mellitus, and involves intricate mechanisms primarily affecting pancreatic β-cells. This bioinformatics-assisted review describes key biological elements of known pathways, such as the forkhead box protein O1/leptin receptor and Janus kinase/signal transducer and activator of transcription 3, and discusses future directions that might contribute to understanding the relationship between obesity, leptin resistance, and metabolic complications (e.g., Rac1/cell division control protein 42 homolog), paving the way for future research on targeted therapeutic interventions.

This review discussed experimental mouse models used in the pre-clinical study of liver fibrosis regression, a pivotal process in preventing the progression of metabolic dysfunction-associated steatohepatitis to irreversible liver cirrhosis. These models provide a valuable resource for understanding the cellular and molecular processes underlying fibrosis regression in different contexts. The primary focus of this review is on the most commonly used models with diet- or hepatotoxin-induced fibrosis, but it also touches upon genetic models and mouse models with biliary atresia or parasite-induced fibrosis. In addition to emphasizing in vivo models, we briefly summarized current in vitro approaches designed for studying fibrosis regression and provided an outlook on evolving methodologies that aim to refine and reduce the number of experimental animals needed for these studies. Together, these models contribute significantly to unraveling the underlying mechanisms of liver fibrosis regression and offer insights into potential therapeutic interventions. By presenting a comprehensive overview of these models and highlighting their respective advantages and limitations, this review serves as a roadmap for future research.

Voriconazole (VRC), a widely used antifungal drug, often causes hepatotoxicity, which presents a significant clinical challenge. Previous studies demonstrated that Astragalus polysaccharide (APS) can regulate VRC metabolism, thereby potentially mitigating its hepatotoxic effects. In this study, we aimed to explore the mechanism by which APS regulates VRC metabolism.

First, we assessed the association of abnormal VRC metabolism with hepatotoxicity using the Roussel Uclaf Causality Assessment Method scale. Second, we conducted a series of basic experiments to verify the promotive effect of APS on VRC metabolism. Various in vitro and in vivo assays, including cytokine profiling, immunohistochemistry, quantitative polymerase chain reaction, metabolite analysis, and drug concentration measurements, were performed using a lipopolysaccharide-induced rat inflammation model. Finally, experiments such as intestinal biodiversity analysis, intestinal clearance assessments, and Bifidobacterium bifidum replenishment were performed to examine the ability of B. bifidum to regulate the expression of the VRC-metabolizing enzyme CYP2C19 through the gut–liver axis.

The results indicated that APS does not have a direct effect on hepatocytes. However, the assessment of gut microbiota function revealed that APS significantly increases the abundance of B. bifidum, which could lead to an anti-inflammatory response in the liver and indirectly enhance VRC metabolism. The dual-luciferase reporter gene assay revealed that APS can hinder the secretion of pro-inflammatory mediators and reduce the inhibitory effect on CYP2C19 transcription through the nuclear factor-κB signaling pathway.

The study offers valuable insights into the mechanism by which APS alleviates VRC-induced liver damage, highlighting its immunomodulatory influence on hepatic tissues and its indirect regulatory control of VRC-metabolizing enzymes within hepatocytes.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently a pressing public health issue associated with adverse outcomes such as cirrhosis, malignancy, transplantation, and mortality. Lifestyle modifications constitute the most effective and fundamental management approach, but they often pose challenges in sustaining long-term clinical benefits. Hence, there is a critical need to enhance our understanding through pharmacological management, which unfortunately remains limited. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a leading treatment in the fields of diabetes and obesity, with recent preclinical and clinical studies indicating significant benefits in the management and treatment of MASLD. Our article begins by reviewing the beneficial therapeutic components of GLP-1RAs in MASLD. Subsequently, from a clinical research perspective, we concluded with the liver outcomes of current primary GLP-1RAs and co-agonists. Finally, we presented our insights on clinical concerns such as appropriate trial endpoints, management of comorbidities, and future developments. In conclusion, the benefits of GLP-1RAs in MASLD are promising, and background therapy involving metabolic modulation may represent one of the future therapeutic paradigms.

Splenic venous hypertension or left-sided portal hypertension is a rare condition caused by an obstruction of the splenic vein. Usually, it presents with upper gastrointestinal bleeding in the absence of liver disease. Etiologies can be classified based on the mechanism of development of splenic vein hypertension: compression, stenosis, inflammation, thrombosis, and surgically decreased splenic venous flow. Diagnosis is established by various imaging modalities and should be suspected in patients with gastric varices in the absence of esophageal varices, splenomegaly, or cirrhosis. The management and prognosis vary depending on the underlying etiology but generally involve reducing splenic venous pressure. The aim of this review was to summarize the etiologies of splenic venous hypertension according to the mechanism of development.

Early detection of hepatocellular carcinoma (HCC) is crucial for improving survival in patients with chronic hepatitis. The GALAD algorithm combines gender (biological sex), age, α-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and protein induced by vitamin K absence or antagonist-II (PIVKA-II) for HCC detection. Similarly, the GAAD algorithm incorporates gender (biological sex), age, AFP, and PIVKA-II. This study aimed to assess the clinical utility of AFP-L3 in the GALAD algorithm and its potential synergies with ultrasound. We compared the clinical performance of GALAD with GAAD; AFP; AFP-L3; and PIVKA-II, with or without ultrasound, in Taiwanese adults.

A total of 439 serum samples were analyzed using a Cobas® e 601 analyzer (healthy controls, n = 200; chronic liver disease controls, n = 177; HCC cases, n = 62). Performance was assessed through receiver operating characteristic curve analyses to calculate the area under the curve.

The area under the curve for differentiating early-stage HCC from patients with chronic liver disease was optimal for PIVKA-II (84.9%), GAAD (79.8%), and GALAD (79.4%), with slightly improved performance for detecting all-stage HCC. Clinical performance was unaffected by disease stage or etiology. Sensitivity for early-stage HCC was highest for GAAD (57.6%) and GALAD (57.6%). Sensitivity for each strategy was further enhanced when combined with ultrasound, regardless of disease stage or etiology (P < 0.01).

These findings indicate that the role of AFP-L3 in the GALAD algorithm is minimal, supporting the use of GAAD for HCC detection. A combination of GAAD, GALAD, or PIVKA-II with ultrasound may improve diagnostic efficiency compared with recommended strategies.

Acute liver failure (ALF) is a life-threatening clinical problem with limited treatment options. Administration of human umbilical cord mesenchymal stem cells (hUC-MSCs) may be a promising approach for ALF. This study aimed to explore the role of hUC-MSCs in the treatment of ALF and the underlying mechanisms.

A mouse model of ALF was induced by lipopolysaccharide and d-galactosamine administration. The therapeutic effects of hUC-MSCs were evaluated by assessing serum enzyme activity, histological appearance, and cell apoptosis in liver tissues. The apoptosis rate was analyzed in AML12 cells. The levels of inflammatory cytokines and the phenotype of RAW264.7 cells co-cultured with hUC-MSCs were detected. The C-Jun N-terminal kinase/nuclear factor-kappa B signaling pathway was studied.

The hUC-MSCs treatment decreased the levels of serum alanine aminotransferase and aspartate aminotransferase, reduced pathological damage, alleviated hepatocyte apoptosis, and reduced mortality in vivo. The hUC-MSCs co-culture reduced the apoptosis rate of AML12 cells in vitro. Moreover, lipopolysaccharide-stimulated RAW264.7 cells had higher levels of tumor necrosis factor-α, interleukin-6, and interleukin-1β and showed more CD86-positive cells, whereas the hUC-MSCs co-culture reduced the levels of the three inflammatory cytokines and increased the ratio of CD206-positive cells. The hUC-MSCs treatment inhibited the activation of phosphorylated (p)-C-Jun N-terminal kinase and p-nuclear factor-kappa B not only in liver tissues but also in AML12 and RAW264.7 cells co-cultured with hUC-MSCs.

hUC-MSCs could alleviate ALF by regulating hepatocyte apoptosis and macrophage polarization, thus hUC-MSC-based cell therapy may be an alternative option for patients with ALF.

Iron overload is a significant complication commonly observed in individuals with β-thalassemia, resulting from enhanced iron absorption due to ineffective erythropoiesis and frequent blood transfusions. Iron overload can lead to severe tissue damage and organ dysfunction, significantly impacting the quality of life for those affected. Additionally, recent research indicates that iron overload may also adversely impact mitochondrial function, further exacerbating the pathophysiology of this disease. Excessive iron accumulation in mitochondria can impair the electron transport chain, reduce adenosine tri phosphate synthesis, and increase the generation of reactive oxygen species, resulting in elevated tissue damage and clinical complications. Emerging evidence suggests that specific mitochondrial DNA (mtDNA) mutations may further contribute to the severity of iron overload in β-thalassemia patients. Currently, the clinical management of iron overload in patients with β-thalassemia primarily relies on conventional iron chelation therapies, aiming to reduce iron burden and prevent tissue damage. However, cases involving mtDNA mutations introduce additional complexities, necessitating personalized treatment approaches. Advances in gene therapy and mitochondrial replacement strategies offer promising avenues for potential targeted interventions. This review provides a comprehensive overview of the mechanisms underlying iron overload in β-thalassemia and its association with mtDNA mutations. It discusses the clinical manifestations, diagnostic challenges, and current treatment options for managing iron overload, while also highlighting emerging research directions and potential therapeutic targets for improved patient care. Ultimately, a better understanding of the complex interplay between iron overload and mtDNA mutations in β-thalassemia will pave the way for innovative strategies to alleviate the disease burden.

High-throughput proteomics has become an exciting field and a potential frontier of modern medicine since the early 2000s. While significant progress has been made in the technical aspects of the field, translating proteomics to clinical applications has been challenging. This review summarizes recent advances in clinical applications of high-throughput proteomics and discusses the associated challenges, advantages, and future directions. We focus on research progress and clinical applications of high-throughput proteomics in breast cancer, bladder cancer, laryngeal squamous cell carcinoma, gastric cancer, colorectal cancer, and coronavirus disease 2019. The future application of high-throughput proteomics will face challenges such as varying protein properties, limitations of statistical modeling, technical and logistical difficulties in data deposition, integration, and harmonization, as well as regulatory requirements for clinical validation and considerations. However, there are several noteworthy advantages of high-throughput proteomics, including the identification of novel global protein networks, the discovery of new proteins, and the synergistic incorporation with other omic data. We look forward to participating in and embracing future advances in high-throughput proteomics, such as proteomics-based single-cell biology and its clinical applications, individualized proteomics, pathology informatics, digital pathology, and deep learning models for high-throughput proteomics. Several new proteomic technologies are noteworthy, including data-independent acquisition mass spectrometry, nanopore-based proteomics, 4-D proteomics, and secondary ion mass spectrometry. In summary, we believe high-throughput proteomics will drastically shift the paradigm of translational research, clinical practice, and public health in the near future.