Pyrrolizidine alkaloids (PAs), widely distributed in plants, are known to induce liver failure. Hepatic platelet accumulation has been reported during the progression of PA-induced liver injury (PA-ILI). This study aimed to investigate the mechanisms underlying platelet accumulation in PA-ILI.

Cases of PA-ILI, non-PA-ILI, and control subjects were collected from patients hospitalized at Zhongshan Hospital, Fudan University (Shanghai, China) between 2012 and 2019. A mouse model of PA-ILI was established using monocrotaline administration. Liver RNA sequencing was performed, and gene interactions were analyzed using the Search Tool for the Retrieval of Interacting Genes/Proteins online database. Low-molecular-weight heparin and recombinant a disintegrin and metalloproteinase with a thrombospondin type I motif member 13 (ADAMTS13) were applied. The necrotic liver area, hepatic platelet accumulation, and von Willebrand factor (VWF) deposition were examined using hematoxylin and eosin staining and immunofluorescence assay.

Hepatic platelet accumulation, necrotic area expansion, and increased VWF expression were observed in both PA-ILI patients and mice. The Search Tool for the Retrieval of Interacting Genes/Proteins database indicated that ADAMTS13 regulates VWF expression and was differentially expressed in the livers of PA-ILI mice. Plasma and hepatic ADAMTS13 levels were significantly downregulated in both PA-ILI patients and mice. Systemic administration of recombinant ADAMTS13 decreased hepatic platelet accumulation, downregulated VWF expression, and mitigated mouse hepatic necrosis.

Hepatic platelet accumulation in PA-ILI was confirmed in both patients and mice. Deficiency of ADAMTS13 plays a critical role in platelet accumulation in PA-ILI, suggesting that ADAMTS13 could be a potential therapeutic target for this condition.

The tumor microenvironment (TME) consists of a complex mix of cellular and non-cellular components, including immune cells, stromal cells, extracellular matrix, cytokines, and growth factors. These elements interact with tumor cells to influence tumorigenesis, growth, invasion, and metastasis. Long noncoding RNAs (lncRNAs)—a class of non-coding RNAs longer than 200 nucleotides—have attracted considerable attention for their roles in regulating gene expression at the epigenetic, transcriptional, and post-transcriptional levels. Emerging evidence suggests that lncRNAs are crucial in shaping the TME by modulating processes such as immune evasion, angiogenesis, metabolic reprogramming, and the maintenance of cancer stem cells. This review provides an overview of the current understanding of lncRNAs in the TME, focusing on their involvement in key signaling pathways and cellular interactions that drive tumor progression. We discussed how lncRNAs contribute to extracellular matrix remodeling, facilitate communication between tumor and stromal cells, and regulate immune cell infiltration and function within the TME. Additionally, we explore the potential of lncRNAs as biomarkers for early cancer detection and prognosis, as well as their promise as therapeutic targets to disrupt tumor-microenvironment crosstalk. The review also addresses challenges in targeting lncRNAs therapeutically, such as ensuring specificity, minimizing off-target effects, and achieving effective in vivo delivery of lncRNA-targeted therapies. Strategies to overcome these challenges include the development of highly specific lncRNA knockout technologies and the use of advanced delivery systems, such as nanoparticles and viral vectors, to precisely target tumor-associated cells. Overall, this review underscores the significant role of lncRNAs in the TME and their potential as novel tools for enhancing cancer diagnosis and treatment. By elucidating the multifaceted roles of lncRNAs in the TME, we aimed to provide insights that could lead to more effective, targeted therapeutic strategies, ultimately advancing cancer research and improving patient care.

Cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) deletions are frequently identified in patients with biliary tract cancer; however, standard treatment options for this genetic alteration are lacking. Here, we present the case of a 64-year-old woman diagnosed with intrahepatic cholangiocarcinoma and hilar lymph node metastasis who underwent radical surgery. Postoperative pathology confirmed moderately differentiated adenocarcinoma. The tumor recurred during the second cycle of adjuvant chemotherapy following surgery, and the metastatic sites included the cranial region, right lung, and right adrenal gland. Genetic analysis revealed a CDKN2A/2B deletion, indicating palbociclib sensitivity. Subsequently, the patient received palbociclib plus lenvatinib as systemic therapy, along with stereotactic radiotherapy for the intracranial lesion. Notably, the right pulmonary metastasis significantly regressed after 12 months of treatment, with the complete disappearance of the intracranial tumor. However, the disease progressed at 32.2 months, with significant enlargement of the right adrenal gland metastasis and new metastasis in the right lung. The progression-free survival and overall survival were 32.2 months and 34.4 months, respectively. In conclusion, our case demonstrates that palbociclib plus lenvatinib is a promising chemotherapy-free second-line treatment for intrahepatic cholangiocarcinoma with a CDKN2A/2B deletion.

Escalating antimicrobial resistance is a global threat, emphasizing the need to explore alternative treatment options. Hence, we aimed to explore the in-vitro activity of ceftazidime-avibactam (CAZ-AVI) in clinical isolates of carbapenem-resistant gram-negative bacteria.

This was an observational, cross-sectional study conducted at the Microbiology Department of Indus Hospital, Karachi, Pakistan, from January 2023 to October 2024. Carbapenem-resistant gram-negative rods isolated from clinical specimens received from the outpatient, emergency, and inpatient departments were included. Consecutive, non-probability sampling was employed for the collection of isolates. Identification of the organisms was confirmed using API® ID strips, and antimicrobial susceptibility for carbapenems and CAZ-AVI was determined via the Kirby-Bauer disc diffusion method.

A total of 158 bacterial isolates were characterized as carbapenem-resistant. Of these, 92 (58%) were Enterobacterales, and 66 (42%) were Pseudomonas aeruginosa. CAZ-AVI was susceptible in 17 (11%) of the isolates, of which four (24%) were Klebsiella spp. and Escherichia coli each, and nine (52%) were P. aeruginosa. CAZ-AVI-susceptible strains were predominant among patients aged 26–50 years (n = 6; 35%), most of whom were females (n = 10; 59%) and inpatients (n = 8; 47%). Clinical samples from patients with urinary tract infections grew the most CAZ-AVI-susceptible strains (n = 9; 53%).

Our study demonstrated low CAZ-AVI susceptibility in our carbapenem-resistant gram-negative bacterial strains. Understanding regional antimicrobial patterns in multidrug-resistant bacteria is crucial for the effective use of CAZ-AVI, along with the strict implementation of strategies for controlling antimicrobial resistance.

The number of molecular abnormalities identified in hematopoietic and lymphocytic neoplasms has grown exponentially over the past decades. Patients with genetic biomarker-matched targeted therapies have experienced significantly improved survival rates. Modern molecular laboratories, equipped with advanced technologies such as next-generation sequencing, can simultaneously test hundreds of genes and thousands of hotspots in a single run with multiple samples analyzed side by side. Bioinformatics tools provide seamless, evidence-based information to determine whether the detected mutations are benign or pathogenic, somatic or germline, druggable or diagnostic. This review is divided into five sections, each aiming to provide a comprehensive overview of the genetic landscape of myeloid and lymphocytic neoplasms. It highlights the challenges and proposes potential solutions to facilitate interpretation and maximize the clinical utility of molecular profiling results.

Mesonephric carcinoma (MC) is a rare type of cervical carcinoma that arises from mesonephric remnants. It is characterized by a mixture of a wide variety of growth patterns and typically exhibits positive immunoreactivity for GATA binding protein 3, thyroid transcription factor 1, and apical common acute lymphoblastic leukemia antigen. A subset of adenocarcinomas in the uterine corpus and ovary with similar morphology and immunophenotype is classified as mesonephric-like adenocarcinoma (MLA) in the current World Health Organization classification. This review aimed to summarize the clinicopathological features of mesonephric remnants, mesonephric hyperplasia, and MC, provide an update on the current understanding of MLA, and highlight the molecular differences between MC and MLA.

A literature review was conducted on mesonephric remnants, mesonephric hyperplasia, MC, and MLA. The clinicopathological and molecular features were summarized from previously published studies and compared across these entities.

Both MC and MLA exhibit a mixture of growth patterns and show immunoreactivity for GATA binding protein 3, thyroid transcription factor 1, and common acute lymphoblastic leukemia antigen. They commonly harbor genetic alterations in KRAS and NRAS. However, key differences exist between these two entities. MC is associated with mesonephric remnants, whereas no such association has been identified for MLA. Additionally, although KRAS and NRAS mutations are common in both, a subset of MLA cases also harbors PIK3CA and/or PTEN mutations, genetic alterations commonly seen in endometrioid adenocarcinoma.

Although the exact pathogenesis of MLA remains unclear, it is favored to originate from Müllerian-derived epithelium undergoing differentiation along the mesonephric pathway, rather than from true mesonephric remnants. Both MC and MLA tend to follow a relatively aggressive clinical course, underscoring the importance of accurate diagnosis.

Wilson’s disease (WD) is a rare autosomal recessive genetic disorder that can be treated with medications. The lack of a single, specific diagnostic indicator leads to diagnostic difficulties, which may result in disease progression to cirrhosis and even liver cancer. Thus, this study aimed to analyze the clinical data, imaging, histopathological manifestations, genetic testing results, and treatment effects of patients with WD hepatic type, and to explore the factors related to WD cirrhosis.

A single-center retrospective study was performed. 48 WD patients with a Leipzig score ≥ 4 were divided into a cirrhosis group and a non-cirrhosis group based on the presence of cirrhosis. Logistic regression analysis and odds ratios were used to describe the strength of association between risk factors and cirrhosis. The predictive value of the model for cirrhosis occurrence was evaluated by calculating the area under the receiver operating characteristic curve and the cutoff value.

All 48 patients diagnosed with WD had liver damage, with males accounting for 54.17%. The median age at diagnosis was 28 years (range: 10.25–40.5 years), and 39.58% of patients had cirrhosis. The most prevalent mutation was c.2333G>T (p.Arg778Leu), found in 41.30% (19/46) of cases. Imaging revealed fatty liver in 31.25% (15/48) of patients and “honeycomb-like” cirrhosis nodules in 73.68% (14/19). Compared with the non-cirrhosis group, the cirrhosis group had a higher positive rate for the Kayser-Fleischer (K-F) ring, older age at diagnosis, and higher levels of immunoglobulin G, but lower levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, white blood cells, and platelets (p < 0.05). Age at diagnosis (odds ratio = 1.072, 95% confidence interval = 1.007–1.142, p = 0.03) and the K-F ring (odds ratio = 18.657, 95% confidence interval = 1.451–239.924, p = 0.025) were independent risk factors for WD-related cirrhosis. The best values of area under the receiver operating characteristic curve for age at diagnosis combined with the K-F ring in predicting WD cirrhosis were 0.909. The average follow-up time for 33 patients was 48.6 months (range: 12–72 months). The biochemical recovery rate was over 60% after 12–72 months of treatment with zinc gluconate and/or penicillamine.

Age at diagnosis, combined with the K-F ring, is a simple and effective risk factor for WD-related cirrhosis. Zinc gluconate and penicillamine are safe and effective treatments.

Blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is essential for non-invasively investigating brain function. However, conventional fMRI methods are limited by low spatial and temporal resolution. This narrative review evaluates recent advancements in deep learning techniques for high-resolution BOLD-fMRI reconstruction, focusing on super-resolution, segmentation, and image registration. A comprehensive literature search was conducted across PubMed, IEEE, Scopus, and Web of Science databases for the period 2000–2023. Studies employing deep learning methods, including convolutional neural networks, transformer-based models, and generative adversarial networks for super-resolution, segmentation, and registration of BOLD-fMRI, were included. Deep learning approaches demonstrated significant improvements in spatial resolution, segmentation accuracy, and registration robustness. Convolutional neural network-based models, particularly generative adversarial networks, notably improved image reconstruction quality and detail preservation. Preliminary studies targeting specific brain regions such as the cerebellum and hippocampus showed promise; however, systematic evaluations across broader brain areas and large-scale clinical validations remain limited. While deep learning techniques have led to substantial advancements in high-resolution BOLD-fMRI reconstruction, future research should focus on standardized protocols, multi-center validation, and improving computational efficiency and model generalization to enhance clinical utility.

Mitochondria are highly dynamic organelles that adapt to cellular stress and metabolic demands through processes such as fission, fusion, mitophagy, and transport, all of which are vital for maintaining cellular signaling and metabolic homeostasis. Fission facilitates mitochondrial division and biogenesis, while fusion enhances mitochondrial fitness and metabolic flexibility by mitigating damage. Together, these processes play a critical role in regulating cellular stress responses and apoptosis. Dysregulation of mitochondrial dynamics has been linked to impaired development and cancer progression, including breast cancer metastasis. A comprehensive understanding of mitochondrial dynamics in breast cancer progression is essential for advancing precision medicine. This review delves into the intricate molecular mechanisms governing mitochondrial biogenesis, fission, fusion, and mitophagy, with a particular focus on the role of mitophagy in maintaining mitochondrial homeostasis and its connection to metastasis progression. Furthermore, it discusses potential therapeutic strategies targeting mitochondrial dynamics and highlights the critical steps necessary to translate these approaches into clinical trials.

Endometrial cancer (EC) is one of the most prevalent malignancies of the female reproductive system and ranks among the three primary types of gynecological cancers. Recent trends indicate a rising incidence of EC in younger patients, highlighting the urgent need for effective early screening strategies. This review examines the challenges associated with early diagnosis and screening, including ambiguous methodologies (e.g., transvaginal ultrasound: sensitivity 80–90%, specificity 60–70%), undefined target populations, and the absence of efficient, cost-effective, minimally invasive solutions (e.g., cytology sensitivity ≤50% in community settings). The article provides an overview of the current landscape and emerging innovations in universal EC screening, highlighting advancements in early detection and diagnosis, such as DNA methylation panels (sensitivity 89–94%, specificity 91–97% in phase II trials) and vibrational spectroscopy (sensitivity 92%, specificity 88% in pilot studies). Additionally, future directions for implementing effective screening strategies are explored, emphasizing the potential of high-accuracy biomarkers and scalable technologies to reduce mortality and healthcare costs.