Paget’s disease of the esophagus is extremely rare, with few cases reported. In this report, we describe a case of recurrent esophageal Paget’s disease coexisting with small cell carcinoma. A 63-year-old man presented with the chief complaint of a rediscovered early esophageal cancer. Endoscopic examination revealed two separate superficial flat tumors in the upper and mid esophagus. Endoscopic submucosal dissection was performed, diagnosing diffuse Paget’s disease (5.5 × 3.5 cm) and a small focus on intramucosal squamous cell carcinoma, respectively. Paget’s cells were also found in the distal and right margins of the first specimen of endoscopic submucosal dissection. Immunohistochemical analysis showed that Paget’s disease diffusely expressed cytokeratin 7 (CK7), CK18, and mucin 6 (MUC6), and focally expressed CD56 and chromogranin A, but not CK5/6, p63, p40, MUC5AC, MUC2, or synaptophysin. A complete absence of p53 and Rb1 was observed in Paget’s disease. However, overexpression of p53 and retention of Rb1 were seen in squamous cell carcinoma. Approximately 27 months later, a prominent tumor was found at the same location as the previous Paget’s disease. Subsequently, radical surgery was performed, and the final pathological evaluation revealed esophageal small cell carcinoma coexisting with Paget’s disease. Moreover, both p53 and Rb1 were completely absent in both Paget’s disease and the small cell carcinoma. This suggests that esophageal Paget’s disease may dedifferentiate and develop into small cell carcinoma. In conclusion, esophageal Paget’s disease can co-occur with invasive carcinomas, including small cell carcinoma, and should be completely resected endoscopically, with close follow-up.

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists are increasingly used in the management of type 2 diabetes mellitus and obesity due to their ability to stimulate insulin secretion, delay gastric emptying, and suppress appetite. The combination of GLP-1 and GIP agonists improves glycemic control and promotes weight loss. However, the introduction of these novel therapies has raised safety concerns, including the risk of cholestatic hepatitis. We report a case of a patient with obesity who was prescribed a GLP-1/GIP dual-receptor agonist as part of his treatment regimen. Importantly, both before the initiation of this therapy and during the course of treatment, the patient was not taking any other medications. Shortly after receiving four doses of the therapy, the patient developed symptoms of severe cholestatic hepatitis, including jaundice and elevated liver enzyme levels. During hospitalization, no alternative causes for the condition were identified, and a liver biopsy confirmed the diagnosis of drug-induced cholestatic hepatitis. This is the first recorded case of cholestatic hepatitis induced by a GLP-1/GIP dual agonist, and it aimed to raise global awareness of this potential side effect.

The Chinese Clinical Practice Guidelines for the Prevention and Treatment of Mother-to-child Transmission of Hepatitis B Virus, developed by the Chinese Society of Infectious Diseases of the Chinese Medical Association in 2019, serves as a valuable reference for standardizing the prevention of mother-to-child transmission in China. As new evidence continues to emerge, it is essential to update these guidelines regularly to optimize clinical practice and research. To this end, the Infectious Disease Physician Branch of the Chinese Medical Doctor Association and the Chinese Society of Infectious Diseases of the Chinese Medical Association, in collaboration with multidisciplinary experts, have updated the guidelines based on the latest domestic and international research advancements and clinical practices, providing up-to-date guidance for clinicians and maternal and child healthcare workers.

Drug-induced hepatotoxicity is a significant clinical issue worldwide. Given the limited treatment options for these liver injuries, understanding the mechanisms and modes of cell death is crucial for identifying novel therapeutic targets. For the past 60 years, reactive oxygen species and iron-dependent lipid peroxidation (LPO) have been hypothesized to be involved in many models of acute drug-induced liver injury. However, this mechanism of toxicity was largely abandoned when apoptosis became the primary focus of cell death research. More recently, ferroptosis—a novel, non-apoptotic form of cell death—was identified in NRAS-mutant HT-1080 fibrosarcoma cells exposed to erastin and other NRLs. Ferroptosis is characterized by glutathione depletion and the impairment of glutathione peroxidase 4 activity, which hinders the detoxification of lipid hydroperoxides. These hydroperoxides then serve as substrates for iron-dependent LPO propagation. This cell death mechanism is now receiving widespread attention, extending well beyond its original identification in cancer research, including in the field of drug-induced liver injury. However, concerns arise when such mechanisms are applied across different cell types and disease states without sufficient validation. This review critically evaluated the historical evidence for iron-dependent LPO as a mechanism of drug-induced hepatotoxicity and explored how these earlier findings have led to the current concept of ferroptosis. Overall, the published data support the idea that multi-layered endogenous antioxidant defense mechanisms in the liver limit the occurrence of pathophysiologically relevant LPO under normal conditions. Only when these defense mechanisms are severely compromised does ferroptosis become a significant mode of drug-induced cell death.

High-mobility group box-1 (HMGB1) is an architectural chromosomal protein with various roles depending on its cellular localization. Extracellular HMGB1 functions as a prototypical damage-associated molecular pattern that triggers inflammation and adaptive immune responses, mediated by specific cell surface receptors, including receptors for advanced glycation end products and toll-like receptors. Post-translational modifications of HMGB1 significantly impact various cellular processes that contribute to the pathogenesis of liver diseases. Recent studies have highlighted the close relationship between HMGB1 and the pathogenesis of acute liver injuries, including acetaminophen-induced liver injury, hepatic ischemia-reperfusion injury, and acute liver failure. In chronic liver diseases, HMGB1 plays a role in nonalcoholic fatty liver disease, alcohol-associated liver disease, liver fibrosis, and hepatocellular carcinoma. Targeting HMGB1 as a therapeutic approach, either by inhibiting its release or blocking its extracellular function, is a promising strategy for treating liver diseases. This review aimed to summarize the available evidence on HMGB1’s role in liver disease, focusing on its multifaceted signaling pathways, impact on disease progression, and the translation of these findings into clinical interventions.

Hepatocellular carcinoma (HCC) is one of the most fatal malignancies. Epigenetic mechanisms have revealed that noncoding RNAs, such as microRNAs (miRNAs) and circular RNAs (circRNAs), are involved in HCC progression. This study aimed to construct a circRNA-miRNA-mRNA network in HCC and validate one axis within the network.

HCC-related transcriptome data were obtained from the Gene Expression Omnibus, and HCC-related genes were sourced from GeneCards to identify differentially expressed circRNAs and miRNAs. The targeting relationships between circRNA-miRNA and miRNA-mRNA interactions were predicted. The involvement of the hsa_circ_0001726/miR-140-3p/KRAS axis in HCC was evaluated through cellular experiments and survival analyses.

We identified six differentially expressed circRNAs in HCC, which were linked to 13 miRNAs and 88 mRNAs. A network containing 34 circRNA-miRNA pairs and 194 miRNA-mRNA pairs was constructed. Cell proliferation and migration assays confirmed the role of hsa_circ_0001726 in promoting HCC progression, possibly through the miR-140-3p/KRAS axis. Survival analysis verified that hsa_circ_0001726 was a prognostic factor for overall survival in patients with HCC. The hsa_circ_0001726/miR-140-3p/KRAS axis also mediates lenvatinib resistance in HCC cells.

The HCC circRNA/miRNA/mRNA network provides new insights into the post-transcriptional regulatory mechanism of HCC. The hsa_circ_0001726/miR-140-3p/KRAS axis is involved in HCC progression and lenvatinib resistance.

The effect of tenofovir amibufenamide (TMF) on blood lipid profiles in patients with chronic hepatitis B (CHB) remains unclear. This study aimed to explore whether TMF affects blood lipids during 48 weeks in patients with CHB.

A total of 91 patients with CHB undergoing TMF treatment for 48 weeks were divided into two groups: Lipid Normal (n = 42) and Lipid Abnormal (n = 49), based on baseline blood lipid levels. Lipid indices, virological responses, and biochemical indicators were compared between the two groups. Clinical observations were further verified through in vitro experiments.

After an average follow-up of 373 ± 121 days, lipid indices in all 91 patients had not significantly changed compared with baseline (total cholesterol: 4.67 vs. 4.69 mmol/L, P = 0.2499; triglycerides: 1.08 vs. 1.04 mmol/L, P = 0.4457; high-density lipoprotein cholesterol: 1.25 vs. 1.25 mmol/L, P = 0.3063; low-density lipoprotein cholesterol: 3.03 vs. 3.02 mmol/L, P = 0.5765). Subgroup comparisons showed lipid indices remained stable. Among treatment-naïve patients (n = 82), complete viral suppression rates were 23.2%, 59.8%, 70.7%, and 86.6% at four, 12, 24, and 48 weeks, respectively. Cellular experiments revealed that TMF did not promote lipid metabolism in primary hepatocytes and AML12 cells.

Regardless of baseline blood lipid characteristics, 48 weeks of antiviral treatment with TMF in patients with CHB had no significant lipid-raising effect.

Bilirubin, the primary breakdown product of hemoproteins, particularly hemoglobin, plays a key role in the diagnosis, prognosis, and monitoring of liver diseases. In acute liver diseases, such as acute liver failure, drug-induced liver injury, and viral hepatitis, bilirubin serves as a biomarker reflecting the extent of hepatocyte loss and liver damage. Chronic liver diseases, including alcohol-related liver disease, chronic hepatitis C virus infection, metabolic dysfunction-associated fatty liver disease, and autoimmune liver diseases, are marked by persistent liver injury and inflammation. Bilirubin levels in chronic liver diseases provide insight into liver function, disease severity, and prognosis. As a versatile biomarker, bilirubin offers valuable information on the pathophysiology of liver diseases and aids in guiding clinical decision-making regarding the treatment of liver diseases and their complications. This review aimed to explore the multifunctional role of bilirubin in liver diseases by analyzing its biological functions beyond its role as a biomarker of liver damage.

Glutathione peroxidase 4 (GPX4) is a key factor in ferroptosis, which is involved in ischemia-reperfusion injury. However, little is known about its role in hepatic ischemia-reperfusion injury (HIRI). This study aimed to investigate the role of GPX4 methylation in ferroptosis during HIRI.

For the in vitro experiments, an oxygen and glucose deprivation cell model was established. For the in vivo experiments, an ischemia-reperfusion model was created by subjecting mice to simulated HIRI. Ferroptosis occurrence, GPX4 promoter methylation, and global methylation levels were then assessed.

Ferroptosis was observed in oxygen and glucose deprivation, characterized by a significant decrease in cellular viability (P < 0.05), an increase in lipid peroxidation (P < 0.01), iron overload (P < 0.05), and down-regulation of GPX4 (P < 0.05). This ferroptosis was exacerbated by GPX4 knockdown (P < 0.01) and mitigated by exogenous glutathione (P < 0.01). Similarly, ferroptosis was evident in mice subjected to HIRI, with a down-regulation of GPX4 mRNA and protein expression (all P < 0.01), and an upregulation of acyl-CoA synthetase long-chain family member 4 mRNA and protein (all P < 0.01), as well as prostaglandin-endoperoxide synthase 2 mRNA and protein expression (all P < 0.05). Methylation levels increased, evidenced by upregulation of DNA methylation transferase expression (P < 0.05) and down-regulation of Ten-eleven translocation family demethylases (P < 0.01), along with an upregulation of GPX4 promoter methylation.

Ferroptosis may be the primary mode of cell death in hepatocytes following ischemia-reperfusion injury. The methylation of the GPX4 promoter and elevated levels of global hepatic methylation are involved in the regulation of ferroptosis.

The brain, traditionally regarded as immune-privileged due to the blood-brain barrier, harbors a sophisticated immune system crucial for maintaining neural health and resilience against various challenges. Microglia, the resident immune cells of the central nervous system, actively monitor their environment, participating in immune surveillance, synaptic pruning, and neuroprotection. Astrocytes also play vital roles by regulating neurotransmitter levels, supporting metabolism, and maintaining the blood-brain barrier integrity. Recent research underscores the involvement of T cells and monocytes in modulating neuroinflammation and immune responses within the brain. Neurological disorders such as Alzheimer’s and Parkinson’s disease highlight the brain’s vulnerability to immune dysregulation. This review aimed to elucidate the role of neuroimmune cells in brain health and the progression of neurological diseases. It aimed to identify critical mechanisms to enhance therapeutic strategies and improve outcomes. Understanding these interactions is essential for developing targeted therapies to mitigate neuroinflammation and preserve cognitive functions. This review critically examines neuroinflammation related to aging and disease, with a focus on neuroimmune cells and their underlying mechanisms. It highlights how chronic inflammation, driven by activated microglia and astrocytes, exacerbates neuronal damage, synaptic dysfunction, and cognitive decline. The disruption of immune privilege in these conditions involves complex pathways that trigger inflammatory responses, impairing essential neural functions. Despite its immune-privileged status, the brain’s immune system, primarily involving microglia and astrocytes, is crucial for maintaining homeostasis and managing illness. Our review strongly suggests that neurological diseases, influenced by genetic, environmental, and aging factors, often involve heightened neuroinflammation. Targeted therapies are needed to address infections, chronic inflammation, and environmental impacts. Additionally, research into mental health disorders and advancements in imaging techniques are critical for understanding immune dysfunction and enhancing treatment strategies.

Helicobacter pylori (H. pylori) infection can cause multiple secondary digestive disorders. Some studies have found that polymorphisms in Toll-like receptor (TLR) genes, including TLR10 rs10004195, may be associated with increased susceptibility to H. pylori infection. Despite conflicting reports, we conducted a meta-analysis to clarify the relationship between these factors.

We conducted an exhaustive review, encompassing all relevant literature up to February 2024, using databases such as PubMed, Embase, Web of Science, and the China National Knowledge Infrastructure. We screened studies based on specific criteria and evaluated their quality using the Newcastle-Ottawa scale. Heterogeneity testing and meta-analysis were performed using Stata 17.0 software, and SPSSAU was used for publication bias evaluation and sensitivity analysis.

Eight of the 487 identified studies met the inclusion criteria, comprising 3,004 and 2,140 individuals in the H. pylori-positive and negative control groups, respectively. Our results demonstrated that individuals carrying the AA genotype at the TLR10 rs10004195 locus had a significantly increased likelihood of H. pylori infection when analyzed using the recessive genetic model (OR: 1.64, CI: 1.04–2.58, p = 0.034). No statistically significant associations were found in the other four genetic models.

Our findings suggest that carrying the TLR10 rs10004195 AA genotype is associated with a significantly elevated risk of H. pylori infection. This information could be used to assess future risk of H. pylori infection in healthy individuals and provide personalized health guidance based on individual genetic polymorphisms.

Data regarding risk factors and long-term outcomes of U.S. patients with biopsy-proven metabolic dysfunction-associated steatotic liver disease (MASLD) are limited. This study aimed to investigate the role of clinical and histologic risk factors on long-term outcomes in patients with MASLD.

A retrospective cohort study of 451 adults with biopsy-proven MASLD was conducted at a U.S. academic hospital from 2012 to 2020. An experienced pathologist evaluated the index liver biopsy. Patients with a prior liver transplant or alternative etiologies of chronic liver disease were excluded. The duration of the risk exposure was determined from the date of the index liver biopsy to an outcome event or the last follow-up examination. Outcome events of interest included incident liver-related events, liver decompensation, and all-cause mortality.

In the final cohort of 406 patients followed for a median of 3.7 years (interquartile range: 4.8 years), 35 patients died, 41 developed hepatic decompensation, and 70 experienced a liver-related event. Among histologic risk factors, stage 3 (adjusted Hazard ratio (aHR) 2.68, 95% confidence interval (CI) 1.18–6.11) and stage 4 (aHR 6.96, 95% CI 3.55–13.64) fibrosis were associated with incident liver-related events compared to stage 0–1 fibrosis. Stage 4 (aHR 8.46, 95% CI 3.26–21.99) fibrosis alone was associated with incident liver decompensation events compared to stage 0–1 fibrosis. Among clinical risk factors, hypertension (aHR 2.58, 95% CI 1.05–6.34) was associated with incident liver decompensation.

In a U.S. single-center cohort of patients with biopsy-proven MASLD, advanced fibrosis was the primary risk factor for incident liver decompensation and liver-related events.

Circulating tumor cells (CTCs), originating from primary neoplastic tissues, infiltrate blood vessels, migrate through the bloodstream, and establish secondary tumor foci. The detection of CTCs holds significant promise for early-stage identification, diagnostic precision, therapeutic monitoring, and prognostic evaluation. It offers a non-invasive approach and has broad clinical relevance in cancer management. This comprehensive review primarily focused on CTCs as biomarkers in the diagnostic, therapeutic, and prognostic surveillance of hepatocellular carcinoma, compared their correlation with key clinical parameters and the identification of gene characteristics. It also highlighted current methodologies in CTC detection. Despite approval by the U.S. Food and Drug Administration for select malignancies, the comprehensive integration of CTCs into routine clinical practice requires procedural standardization and a deeper understanding of the underlying molecular intricacies. The challenges in CTC detection, including limited quantity, technical impediments, and cellular heterogeneity, call for concerted and further investigational efforts to advance precision in cancer diagnostics and prognostication, thus realizing the objectives of precise and personalized medicine.

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.

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.

Gastroschisis is the most common form of congenital paramedian or lateral anterior abdominal wall defect, characterized by the herniation of viscera. The evolution in the management of gastroschisis, from zero-to-hero performance (from uniform fatality to nearly 95% survival over the last six decades), is a spectacular success story in neonatal surgery. This review aims to address the embryopathogenesis, epidemiology, diagnosis, and surgical management of gastroschisis. Based on the literature and our experimental and clinical research, it is evident that gastroschisis is formed by raised intra-luminal and intra-abdominal pressure in combination with potential weak points. Young mothers who struggle to meet their macro- and micronutrient requirements can suffer stress to the psycho-neuro-endocrine-target organ axis. This can place a burden on the placenta, especially if exacerbated by smoking, alcohol, drugs, and other toxins. This burden on the mother's axis can lead to fetal distress and a similar burden on the same axis in the fetus. Ultimately, if distress in the fetal axis stimulates a "fight or flight" response via the sacral parasympathetic nervous system, consequent colorectal secreto-motility disorder of the hindgut and of the small left colon can result in partial functional obstruction of the hindgut. If pressure is thus built up on the proximal colon and on an intact ileocecal valve, leading to a blind loop obstruction, sufficient force can be created to herniate the bowel through a defect at any of three key points of weakness in the abdominal wall. The most vulnerable of these is in the right paraumbilical region, the next is in any spaces between the costochondral junctions and the muscle attachments, and the third is through neurovascular gaps in the linea semilunaris. If the ileocecal valve then becomes incompetent, variants of gastroschisis may occur. The fetus, particularly the peritoneum, always has a tendency to heal defects quickly, but this can result in secondary events in the eviscerated bowel, causing both closing and closed gastroschisis with vanishing organs. Recent technological advances in pre-formed silastic silo innovation, prenatal diagnosis and monitoring for closing gastroschisis, perinatal management, percutaneous central long lines, and innovative minimally invasive bedside procedures have all made significant contributions.

Percutaneous endoscopic gastrostomy (PEG) tube placement is a common procedure used to provide medium- and long-term enteral nutrition to patients. Although generally considered safe, PEG tube placement can be associated with various potential complications. We report a case of gastrocolocutaneous fistula formation in a patient who presented with severe abdominal pain, new-onset diarrhea, and feculent emesis nine days after PEG tube placement. Awareness of this rare complication can facilitate the recognition of colonic perforation during gastrostomy tube placement and enable early detection of the complication post-procedurally. Additionally, we discuss various techniques that may be employed to prevent this complication during PEG tube placement.

Early determination of prognosis in patients with acute-on-chronic liver failure (ACLF) is crucial for optimizing treatment options and liver allocation. This study aimed to identify risk factors associated with ACLF and to develop new prognostic models that accurately predict patient outcomes.

We retrospectively selected 1,952 hospitalized patients diagnosed with ACLF between January 2010 and June 2018. This cohort was used to develop new prognostic scores, which were subsequently validated in external groups.

The study included 1,386 ACLF patients and identified six independent predictors of 28-day mortality through multivariate analysis (all p < 0.05). The new score, based on a multivariate regression model, demonstrated superior predictive accuracy for both 28-day and 90-day mortalities, with Areas under the ROC curves of 0.863 and 0.853, respectively (all p < 0.05). This score can be used to stratify the risk of mortality among ACLF patients with ACLF, showing a significant difference in survival between patients categorized by the cut-off value (log-rank (Mantel–Cox) χ2 = 487.574 and 606.441, p = 0.000). Additionally, the new model exhibited good robustness in two external cohorts.

This study presents a refined prognostic model, the Model for end-stage liver disease-complication score, which accurately predicts short-term mortality in ACLF patients. This model offers a new perspective and tool for improved clinical decision-making and short-term prognostic assessment in ACLF patients.

A growing body of literature has demonstrated improved quality of life in cancer patients who utilize web-based patient portals; however, no studies have investigated their impact on objective clinical measures. The study aimed to evaluate the impact of patient portal utilization on clinical outcomes in cancer care. Patient portal platforms provide patients with direct access to their providers through messaging, medication requests, and other tools. There is a knowledge gap in the literature regarding whether electronic patient portals enhance outcomes in cancer care.

This study is a retrospective analysis of 791 patients with multiple myeloma within the Scripps Health system. The effect of MyScripps electronic patient portal use on unplanned hospital visits and mortality was assessed. Outcomes were also evaluated in relation to the age-adjusted Charlson comorbidity index and chemotherapy use.

Results showed that older, male, Hispanic, and Spanish-speaking patients had lower portal utilization. Those with inactive portal status had higher rates of unplanned hospital visits and mortality. Inactive portal status was an independent predictor of unplanned hospital visits in two multivariable logistic regression analyses. A logistic regression model investigating the interaction between patient portal use and age-adjusted Charlson comorbidity index revealed that active portal status remained a predictor of unplanned hospital visits.

This study highlights the potential to improve clinical outcomes among patients with multiple myeloma, particularly in vulnerable communities, by increasing access to electronic patient portals.