Large granular lymphocytic leukemias (LGLLs), including T-cell LGLL and natural kill (NK)-cell LGLL variants, are rare lymphoproliferative disorders characterized by the chronic proliferation of cytotoxic lymphocytes. Despite recent advancements, challenges remain in distinguishing these entities from one another and from related disorders, such as T-cell prolymphocytic leukemia, adult T-cell leukemia/lymphoma, Sézary syndrome, and aggressive NK-cell leukemia, owing to overlapping clinical and morphologic features. This article aims to review the role of molecular and immunophenotypic markers in guiding diagnosis and prognosis of LGLLs, with brief review of their clinical and morphologic features by synthesizing current advances in molecular pathogenesis, immunophenotypic profiling, and updated World Health Organization (WHO) classification criteria in order to enhance diagnostic precision, improve prognostic assessment, and inform personalized treatment strategies for these challenging disorders.

Literature was searched through Pubmed and the recently published 5th WHO classification criteria. Articles were reviewed and analyzed with emphasis on recent molecular and cytogenetic insights.

A total of 106 publications were reviewed, and the recent molecular insights—focusing on those concerning STAT3 mutations in T-cell LGLL and TET2 mutations in NK-cell LGLL which have refined diagnostic frameworks, though gaps persist in understanding their clinical relevance and variability.

By providing a comparative analysis of large granular lymphocytic leukemias and their differential diagnoses in cooperation of the current advances in molecular pathogenesis, immunophenotypic profiling, and updated WHO classification criteria, this work aimed to enhance diagnostic precision, improve prognostic assessment, and inform personalized treatment strategies for these challenging LGLLs.

The diagnostic value of primary biliary cholangitis (PBC)-specific antibodies in patients with elevated alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels, and other identifiable causes, was unclear. Our study aimed to determine whether etiological treatments in PBC-specific antibody-positive patients could improve liver biochemical tests, thereby distinguishing them from individuals with PBC.

We enrolled patients who were positive for PBC-specific antibodies and elevated ALP and/or GGT levels but with other identifiable etiologies. Changes in liver biochemistry following non-ursodeoxycholic acid etiological treatments were monitored.

A total of 155 patients with positive PBC-specific antibodies and elevated ALP and/or GGT levels due to non-PBC diseases were enrolled. Among them, 100 patients were diagnosed with non-PBC liver diseases, mainly metabolic-associated fatty liver disease, drug-induced liver injury, and autoimmune hepatitis. Additionally, 55 patients had non-liver diseases, predominantly connective tissue diseases. The median follow-up duration was 15.9 (4.7–25.6) months. Among 141 patients who completed follow-up after receiving etiological treatments, 85.1% (120/141) showed improvement in ALP and/or GGT levels, with 51.8% (73/141) achieving normalization of both ALP and GGT. However, 68 patients continued to exhibit elevated ALP and/or GGT, with 55 patients displaying isolated GGT elevation and 11 patients showing liver histological changes not consistent with PBC.

PBC-specific antibodies, along with elevated ALP and GGT levels, may occur in various non-PBC diseases. Etiological treatments may improve or even resolve cholestatic biochemistry. For these patients, initiating etiological treatment rather than immediately starting ursodeoxycholic acid therapy would be justified.

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract and primarily includes ulcerative colitis and Crohn’s disease. As the number of patients suffering from IBD increases, diagnosis and treatment have become pressing yet challenging tasks. A major challenge is that patients with IBD often do not exhibit characteristic symptoms, making it difficult to distinguish IBD from other intestinal abnormalities. Endoscopy is the most conventional method used to diagnose IBD; however, this technique is invasive and costly. Therefore, there is a need to develop affordable, non-invasive diagnostic methods, which underscores the importance of identifying biomarkers specific to IBD. It is now well established that the gut microbiome plays a significant role in the development of IBD, and changes in the abundance of various gut organisms have been widely studied to identify microbial signatures associated with the disease. This review discusses the current state of knowledge regarding biomarkers in IBD, with a primary focus on the gut microbiome, associated metabolic signatures, and their links with immunological biomarkers. These biomarkers will help propose an integrative model to better understand the pathophysiology of this complex disease. Such an integrated approach also offers insights into potential therapeutic targets for designing more effective treatment strategies for patients.

The proto-oncogene c-Fos is known as a reliable marker of cell activation, which is immediately induced after a new stimulus in specific brain regions, depending on the nature of the stimulus applied. However, the expression of c-Fos is increased in Alzheimer’s disease (AD) and contributes to amyloid β-peptide-induced neurotoxicity. This review attempted to focus on the role of c-Fos in learning and memory in both healthy brain and AD, emphasizing on possible mechanisms. Comparing the available findings, regarding learning and memory, c-Fos expression leads to memory formation through ERK (extracellular signal-regulated kinase)/CREB (cAMP response element-binding protein) and long-term potentiation, while it is down regulated after the repetition and habituation of stimuli. However, its overexpression in neurons and glia of AD, contributes to cognitive deficits and neuronal loss, which represents a defect in its ability to habituate to repeated stimuli. Also, expression pattern in glial is associated with constitutive CREB activation following increasing amyloid beta (Aβ), activation transcription factor (ATF3), and cytochrome c in apoptosis pathways. Thus, two contradictory roles of c-Fos in the healthy brain and AD, reveal more complexity in c-Fos up and down stream signaling pathways, bioavailability, and sensitivity. Future studies focusing on c-Fos modulation, might offer promising strategies to mitigate cognitive decline in AD.

T-cell receptor (TCR) sequencing provides a novel platform for insight into and characterization of intricate T-cell profiles, advancing the understanding of tumor immune heterogeneity. Recently, transarterial chemoembolization (TACE) combined with systemic therapy has become the recommended regimen for advanced hepatocellular carcinoma. The regulation of the immune microenvironment after TACE and its impact on tumor progression and recurrence has been a focus of research. By examining and tracking fluctuations in the TCR repertoire following combination treatment, novel perspectives on the modulation of the tumor microenvironment post-TACE and the underlying mechanisms governing tumor progression and recurrence can be gained. Clarifying the distinctive metrics and dynamic alterations of the TCR repertoire within the context of combination therapy is imperative for understanding the mechanisms of anti-tumor immunity, assessing efficacy, exploiting novel treatments, and further advancing precision oncology in the treatment of hepatocellular carcinoma. In this review, we initially summarized the fundamental characteristics of TCR repertoire and depicted immune microenvironment remodeling after TACE. Ultimately, we illustrated the prospective applications of TCR repertoires in TACE combined with systemic therapy.

Breast cancer remains one of the leading causes of cancer-related deaths worldwide. Early detection of breast cancer significantly improves outcomes and survival rates, minimizing treatments. Imaging techniques are critical in identifying abnormalities and diagnosing breast cancer at its earliest stages, often before clinical symptoms emerge. Mammography remains standard for screening in average-risk women, while supplementary methods like ultrasound, magnetic resonance imaging, and tomosynthesis enhance detection rates, particularly in women with dense breasts or those at high risk. Given that certain factors, such as family history, age, genetic mutations, and breast density, affect the risk of developing breast cancer, some women may benefit from earlier or more frequent screenings. Personalized screening protocols are becoming more common, tailoring the type and frequency of imaging to the individual’s risk profile. Newer technologies, such as molecular breast imaging and contrast-enhanced mammography show promise but require further validation for widespread use. In conclusion, imaging techniques including mammography, ultrasound, magnetic resonance imaging, and newer technologies like three-dimensional mammography and molecular breast imaging are essential tools in the early detection of breast cancer, leading to better outcomes for patients. This literature review provides an overview of current breast cancer imaging methods, their role in early diagnosis, and their effectiveness and limitations.

Achalasia is a rare esophageal motility disorder characterized by the inability of the lower esophageal sphincter to relax and the absence of normal esophageal peristalsis. This condition leads to difficulties in swallowing (dysphagia), regurgitation of food, and chest pain. Clinical observations suggest an association between achalasia and esophageal tumors, as achalasia can increase the risk of developing esophageal cancer. We explore the pathophysiology of achalasia, its clinical manifestations, and the associated risk of esophageal malignancies, supported by recent research and clinical evidence, including specific case studies.

Fluorescence navigation is a novel technique for accurately identifying hepatocellular carcinoma (HCC) lesions during hepatectomy, enabling real-time visualization. Indocyanine green-based fluorescence guidance has been commonly used to demarcate HCC lesion boundaries, but it cannot distinguish between benign and malignant liver tumors. This review focused on the clinical applications and limitations of indocyanine green, as well as recent advances in novel fluorescent probes for fluorescence-guided surgery of HCC. It covers traditional fluorescent imaging probes such as enzymes, reactive oxygen species, reactive sulfur species, and pH-sensitive probes, followed by an introduction to aggregation-induced emission probes. Aggregation-induced emission probes exhibit strong fluorescence, low background signals, excellent biocompatibility, and high photostability in the aggregate state, but show no fluorescence in dilute solutions. Design strategies for these probes may offer insights for developing novel fluorescent probes for the real-time identification and navigation of HCC during surgery.