There are no intraepithelial eosinophils present in the normal esophageal mucosa. It is well established that gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE) individually can result in esophageal eosinophilia and that the two disorders frequently coexist in the same patient. Nevertheless, the first step in the diagnostic algorithm for patients with esophageal symptoms associated with esophageal eosinophilia is to exclude non-EoE disorders that can cause esophageal eosinophilia, including GERD. While it is clear that GERD without EoE can cause low-level esophageal eosinophilia, it is less clear whether GERD alone can induce EoE-level esophageal eosinophilia (i.e., ≥15 eosinophils per high-power field). In this report, we have reviewed mechanisms by which reflux might induce eosinophilia in the esophagus and assessed studies suggesting that GERD alone can induce EoE-level esophageal eosinophilia. Studies on the latter issue have suffered from numerous shortcomings, including the use of outmoded or dubious methods for identifying GERD. Many of these studies were published prior to the realization that EoE can respond to proton pump inhibitor treatment. Our review of these studies suggests that GERD alone rarely, if ever, causes EoE-level eosinophilia (perhaps <1% of cases). For patients with definitive evidence of GERD associated with EoE-level esophageal eosinophilia but without endoscopic or clinical features of EoE, it is impossible to determine whether the eosinophilia is caused solely by GERD, by underlying but unrelated EoE that does not manifest typical features, or by EoE driven by GERD-induced defects, such as impaired esophageal barrier function. Until better diagnostic tests for EoE become available, this situation will remain a clinical conundrum.

Rheumatoid arthritis (RA) is an inflammatory arthritis characterized by chronic joint inflammation, cartilage degradation, and bone erosion. ELK3 is a transcriptional repressor that can affect cell proliferation, migration, invasion, apoptosis, and other cellular processes. The study aimed to clarify the effect of ELK3 in the biological activity and ferroptosis phenotype of RA fibroblast-like synoviocytes (FLS), and to reveal its molecular mechanism in regulating ferroptosis in RA FLS.

We investigated the impact of ELK3 on the biological activity and ferroptosis phenotype of RA FLS using real-time quantitative polymerase chain reaction, immunohistochemistry, Transwell assay, CCK-8 assay, and ferroptosis-related indicator kit. The molecular mechanism of ELK3 in RA FLS was further explored using Western blot, chromatin immunoprecipitation polymerase chain reaction, and other experiments.

ELK3 was highly expressed in RA. Silencing ELK3 inhibited the invasion and proliferation of RA FLS (both p < 0.05). After silencing ELK3 in imidazole ketone erastin-induced RA FLS, intracellular reactive oxygen species, lipid peroxidation levels, ferrous ion content, 4-Hydroxynonenal levels, and Malondialdehyde concentrations all increased. Additionally, ELK3 affects ferroptosis in RA FLS by regulating kelch-like ECH-associated protein 1 (p < 0.05).

Silencing ELK3 leads to decreased invasion and proliferation of RA FLS, affecting their biological activity. ELK3 inhibits ferroptosis by suppressing its transcriptional activity through binding to the kelch-like ECH-associated protein 1 promoter. This suggests that ELK3 may be a potential target for RA therapy.

The causal biomarkers for metabolic dysfunction-associated steatotic liver disease (MASLD) and their clinical value remain unclear. In this study, we aimed to identify biomarkers for MASLD and evaluate their diagnostic and prognostic significance.

We conducted a Mendelian randomization analysis to assess the causal effects of 2,925 molecular biomarkers (from proteomics data) and 35 clinical biomarkers on MASLD. Mediation analysis was performed to determine whether clinical biomarkers mediated the effects of molecular biomarkers. The association between key clinical biomarkers and MASLD was externally validated in a hospital-based cohort (n = 415). A machine learning–based diagnostic model for MASLD was developed and validated using the identified molecular biomarkers. Prognostic significance was evaluated for both molecular and clinical biomarkers.

Six molecular biomarkers—including canopy FGF signaling regulator 4 (CNPY4), ectonucleoside triphosphate diphosphohydrolase 6 (ENTPD6), and major histocompatibility complex, class I, A (HLA-A)—and eight clinical biomarkers (e.g., serum total protein (STP)) were identified as causally related to MASLD. STP partially mediated the effect of HLA-A on MASLD (23.61%) and was associated with MASLD in the external cohort (odds ratio = 1.080, 95% confidence interval: 1.011–1.155). A random forest model demonstrated high diagnostic performance (AUC = 0.941 in training; 0.875 in validation). High expression levels of CNPY4 and ENTPD6 were associated with the development of and poorer survival from hepatocellular carcinoma. Low STP (<60 g/L) predicted all-cause mortality (HR = 2.50, 95% confidence interval: 1.22–5.09).

This study identifies six causal molecular biomarkers (e.g., CNPY4, ENTPD6, HLA-A) and eight clinical biomarkers for MASLD. Notably, STP mediates the effect of HLA-A on MASLD and is associated with all-cause mortality.

Extrahepatic portosystemic shunts (EPS) are abnormal connections between the portal and systemic circulations. Acquired EPS occur most commonly in adults and are usually associated with portal hypertension due to cirrhosis. Acquired EPS cases can be further subdivided into two types: variceal (pre-existing) EPS and non-variceal EPS (NVEPS). Variceal EPS arise from originally small vessels with pre-existing dual portal and systemic drainage. Due to elevated portal pressure, these vessels dilate and undergo a reversal of flow, sending blood back to the systemic circulation. A much less common and, therefore, underappreciated subset of acquired EPS is NVEPS, which consists of aberrant connections that did not previously exist between the portal vein and large systemic vessels, usually in the presence of portal hypertension. Neoangiogenesis results in the development of abnormal anastomoses between the portal vein and other large veins, resulting in splenorenal, gastrorenal, portocaval, and mesocaval shunts. While not uncommon, they are frequently overlooked in the diagnosis and treatment of portal hypertension and can pose significant diagnostic and therapeutic challenges. Because the treatment of variceal EPS and NVEPS can differ markedly, it is important to correctly diagnose NVEPS and institute appropriate management. The aim of this article was to review acquired EPS, with particular attention to NVEPS, updating the pathogenesis, diagnosis, and treatment.

Metabolic-associated steatohepatitis (MASH) is an advanced and progressive liver disease that potentially causes cirrhosis and hepatocellular carcinoma. Exercise is a crucial and effective intervention for ameliorating metabolic dysfunction-associated steatotic liver disease. This study aimed to provide a comprehensive understanding of the underlying mechanisms of MASH, which benefit a broad spectrum of MASH patients, including those who have difficulty engaging in physical activity.

We established a mouse model of MASH and selectively knocked down L-type amino acid transporter 1 and alanine-serine-cysteine transporter 2. Mice were fed a high-fat high-cholesterol diet and subjected to either short- or long-term exercise regimens. We assessed the phosphorylation and activity of branched-chain alpha-keto acid dehydrogenase (BCKDH) as well as branched-chain amino acid (BCAA) content in skeletal muscle following exercise.

Short-term exercise significantly reduced hepatic steatosis and inflammation without causing notable changes in body weight. It also enhanced BCKDH activity in skeletal muscle and decreased hepatic BCAA accumulation. Muscle-specific overexpression of BCKDH further promoted BCAA catabolism and significantly attenuated hepatic steatosis and inflammation in high-fat high-cholesterol-fed mice. In contrast, muscle-specific L-type amino acid transporter 1 knockdown, which suppresses BCAA uptake, markedly abolished these beneficial effects. Interestingly, BCKDH overexpression in muscle increased glutamine levels in both the blood and liver. Hepatic alanine-serine-cysteine transporter 2 knockdown, which inhibited glutamine uptake, lessened the protective effect of exercise on MASH. Further in vitro study revealed that glutamine derived from myocytes improved redox homeostasis and inhibited lipid accumulation in hepatocytes.

Short-term exercise enhances BCAA catabolism in skeletal muscle and promotes glutamine production, which circulates to the liver to improve redox balance and alleviate MASH.

Soft tissue cytopathology plays a vital role in the diagnosis and management of soft tissue neoplasms, necessitating a standardized classification system to improve diagnostic accuracy and guide clinical decision-making. This article provides a concise review of the World Health Organization (WHO) Reporting System for Soft Tissue Cytopathology and presents a practical diagnostic approach to soft tissue cytopathology.

The WHO Reporting System is reviewed in conjunction with relevant literature. The reporting system employs a six-category framework: non-diagnostic, benign, atypical, soft tissue neoplasm of uncertain malignant potential, suspicious for malignancy, and malignant. Each category is associated with a corresponding risk of malignancy and recommended clinical management guidelines. This classification aligns with the WHO Classification of Soft Tissue and Bone Tumours (5th edition) and incorporates cytomorphologic features, ancillary studies, and clinical correlation to enhance diagnostic reproducibility and communication among pathologists and clinicians.

The system supports a probabilistic approach to risk stratification, enabling more consistent diagnostic and therapeutic strategies.

As molecular diagnostics and immunocytochemistry continue to advance, this framework provides a robust foundation for the interpretation of soft tissue fine-needle aspiration biopsies and optimized patient care.

Patients with chronic hepatitis B virus (HBV) infection in the immune-tolerant phase may still experience hepatic inflammation and disease progression, and could benefit from early antiviral treatment. This study aimed to investigate changes in the cumulative hepatitis B surface antigen (HBsAg)/HBV DNA ratio in immune-tolerant patients during the transition to the immune-active phase, and to evaluate its potential in predicting the risk of disease progression.

This longitudinal study included 127 untreated immune-tolerant patients, who were followed for up to 10 years. An independent cohort of 109 subjects was retrospectively enrolled for external validation. The relationship between the cumulative HBsAg/HBV DNA ratio and the duration of immune tolerance or transition to the immune-active phase was examined. The predictive value of the ratio was assessed and validated.

The relationship between the cumulative HBsAg/HBV DNA ratio and disease progression risk showed a non-linear pattern: below a ratio of 1.791, the risk of disease progression decreased rapidly as the ratio increased; above 1.791, the risk plateaued. The area under the curve for predicting disease progression was 0.67, 0.64, and 0.85 for cumulative HBsAg, HBV DNA, and the HBsAg/HBV DNA ratio, respectively. Multivariable Cox regression analysis revealed the cumulative HBsAg/HBV DNA ratio as an independent predictor of disease progression, with higher ratios associated with a lower risk. Prediction models incorporating this ratio were developed and externally validated, demonstrating strong performance and clinical utility.

The cumulative HBsAg/HBV DNA ratio is an independent factor influencing the duration of immune tolerance and shows superior predictive performance. It may serve as a valuable marker for assessing the risk of disease progression in patients with chronic HBV infection.

Proper nutritional management has been shown to reduce complications and lead to better clinical outcomes. However, inaccurate nutritional screening and assessment, inappropriate nutrition support, and deviations from suggested guidelines were observed in clinical practice. We aimed to investigate the nutritional status and support of hospitalized patients with neurological diseases to identify deficiencies in nutritional assessment and treatment.

A self-designed questionnaire, developed through a literature review, group discussions, and expert consultation, was converted into an electronic form to conduct a cross-sectional survey in a tertiary-level general hospital. The patients’ basic information and the first nutrition assessment were filled out upon admission. The final nutrition assessment were logged at discharge, transfer out, or death. Two-person cross-entry was used to ensure the accuracy of data input.

A total of 620 patients were enrolled in this study. Of these, 24.4% were at nutritional risk upon admission, and 22.7% were identified as at nutritional risk in the final assessment. There were no statistically significant differences in nutritional status between the first and final assessments, except for serum albumin concentration. A total of 118 patients (19.0%) received nutrition therapy. Complications occurred in 35 (45.5%) patients treated with enteral nutrition and 29 (30.5%) patients treated with parenteral nutrition.

The incidence of nutritional risk in inpatients with neurological diseases enrolled in this study was relatively low. However, nutritional treatment in this study was not sufficiently standardized. Nurses are needed to receive relevant professional training to improve quality of nutritional interventions.

Amyotrophic lateral sclerosis (ALS) and other motor neuron diseases (MNDs) are major global causes of death. However, their global incidence, mortality, and disability-adjusted life years remain largely unknown, despite their importance for disease prevention and resource allocation. We therefore examined the global epidemiology of ALS/MNDs.

This study analyzed data from the Global Burden of Disease 2021 database for 204 regions (1990–2021), focusing on ALS/MNDs. Data from the world, China, and the G8 countries were analyzed separately. Age-standardized incidence rates were reported for the 1990s, 2000s, 2010s, and 2020s.

A rising global burden of ALS/MNDs, with significant variations across regions and levels of the social development index, was observed in the Global Burden of Disease database. A significant overlap of etiology between neurological diseases and ALS was also identified. Among the G8 countries and China, China and the USA exhibited the highest prevalence rates in the 1990s, 2000s, 2010s, and 2020s, with China showing 3.3 per 10,000 and the USA 4.0 per 10,000 in the 2020s.

Understanding the common etiologies of ALS/MNDs is key to their effective control. Recommended strategies include pollution control, chemical and radiation safety management, disease monitoring, public health education, multi-departmental collaboration, and scientific research.

This study investigates the potential of methyl eugenol (ME), a compound found in the essential oils of various plants, to inhibit oxidative stress and its impact on diseases associated with this process. ME has been shown to possess antioxidant properties and antiproliferative activity in several cancers. It also demonstrates neuroprotective potential in conditions such as Alzheimer’s disease and ischemic brain injury. The mechanism of action involves the activation of the nuclear factor erythroid 2-related factor 2, which facilitates the transcription of antioxidant genes and modulation of pathways such as AMP-activated protein kinase/glycogen synthase kinase 3 beta, thereby reducing the production of reactive oxygen species and pro-inflammatory cytokines. However, research has identified potential toxicological risks associated with ME, including hepatotoxicity and changes in the gut microbiota. These findings highlight the need for caution when considering prolonged exposure to this compound.