Chronic liver cirrhosis (LC) and acute-on-chronic liver failure (ACLF) are interconnected hepatic disorders associated with substantial morbidity and mortality. Despite their distinct clinical characteristics, both conditions share common pathogenic pathways that remain inadequately understood. This study aimed to identify shared gene signatures and elucidate underlying molecular mechanisms.

In this study, we employed Weighted Gene Co-Expression Network Analysis to explore transcriptomic data from the Gene Expression Omnibus for LC and ACLF.

Key co-expression modules enriched with genes involved in glycolysis and gluconeogenesis pathways were identified, implicating metabolic dysfunction as a central feature in both conditions. Furthermore, microRNA analysis revealed that hsa-miR-122 and hsa-miR-194 play pivotal roles in regulating these metabolic pathways, potentially contributing to immune dysregulation.

Our findings indicate that these shared molecular mechanisms are critical in the progression from LC to ACLF, providing novel insights into potential therapeutic targets for mitigating disease severity and improving clinical outcomes.

The incidence of early-onset pancreatic cancer (EOPC) is rising, yet optimal treatment strategies remain unclear. While adjuvant chemotherapy (ACT) has shown survival benefits in pancreatic ductal adenocarcinoma, its specific role in EOPC patients following neoadjuvant chemotherapy (NACT) and surgery remains underexplored. This study aimed to assess the clinical benefit of ACT in EOPC patients after NACT.

This retrospective cohort study analyzed pancreatic ductal adenocarcinoma patients from the SEER database (2006–2019) who received NACT followed by curative resection. Propensity score matching (1:1) was used to balance covariates such as tumor, lymph node, metastasis stage, chemotherapy, and radiotherapy. Overall survival (OS) and cancer-specific survival (CSS) were compared between patients with EOPC (<50 years) and average-onset pancreatic cancer (AOPC, ≥50 years). Multivariate Cox regression analysis was performed to identify prognostic factors.

After propensity score matching (124 EOPC vs. 124 AOPC), EOPC patients had significantly longer median OS (41.0 vs. 29.0 months, P = 0.042) and CSS (48.0 vs. 30.0 months, P = 0.016). ACT was an independent prognostic factor for EOPC (OS: hazard ratio = 0.495, 95% confidence interval 0.271–0.903, P = 0.022; CSS: hazard ratio = 0.419, 95% confidence interval 0.219–0.803, P = 0.009), but not for AOPC (P > 0.05). Subgroup analysis revealed that EOPC patients with tumor, lymph node, metastasis stage II disease or those receiving ACT derived the greatest survival benefit.

EOPC patients exhibit superior survival following NACT and surgical resection compared to AOPC, with ACT further enhancing outcomes in this subgroup. These findings support the use of tailored ACT for EOPC and underscore the need for prospective validation.

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.

Acute hepatitis E (AHE) in the elderly can lead to severe complications including liver failure and mortality, yet the epidemiological landscape remains poorly characterized. This study aimed to assess the burden, trends, and health inequalities of AHE among the elderly over the past three decades, and to further predict its changes by 2030.

Data on AHE in the elderly were obtained from the Global Burden of Disease 2021. The burden of AHE was analyzed by trends, decomposition, cross-country inequalities, and predictive analysis.

In 2021, the global incidence and Disability-Adjusted Life Years (DALYs) for AHE among the elderly were recorded as 1,130,013.35 and 20,084.77, respectively. Although there were significant differences in the incidence and DALYs across countries, the number of incident cases increased from 1990 to 2021, with a slight rise in age-standardized rates, while the number and age-standardized rate of DALYs showed a declining trend. Decomposition analysis revealed that population growth and aging are the drivers of changes in incidence, while epidemiological changes somewhat offset the increases in DALYs driven by population growth. Low socio-demographic index countries bear a disproportionate burden of elderly AHE, although inequality gaps have narrowed over time. Notably, up to 2030, the number of incident cases and DALYs will continue increasing. The burden in elderly women was more pronounced than in men.

The burden of elderly AHE, as a major public health issue, remains substantial. While cross-country inequities have been alleviated over time, the pressure on lower socio-demographic index countries to control the disease remains high. AHE in elderly women requires further attention. This emphasizes the significant challenges faced in controlling and managing elderly AHE.

Immunoinflammatory skin diseases are characterized by an imbalance in immune homeostasis, and their chronic inflammatory processes involve a complex regulatory network of CD4+ T cell differentiation. With the widespread use of biologics (e.g., interleukin-17/interleukin-23 inhibitors) in psoriasis, atopic dermatitis, and other diseases, the adverse effects triggered by the phenomenon of CD4+ T cell-mediated immune drift have attracted significant attention, with the skin being the primary target as an immune organ. In this paper, we provide a review of the clinical features of the skin and the mechanisms of immune drift caused by different types of biologics, as well as the therapeutic modalities.

Brain metastases from ovarian cancer (BMFOC) are rare but associated with poor prognosis. This study aimed to evaluate the efficacy and safety of Gamma Knife stereotactic radiosurgery (GKSRS) in managing patients with BMFOC.

A retrospective analysis was conducted on 22 patients with BMFOC who were treated with GKSRS between January 2015 and May 2019. The median age at the start of treatment was 57.7 years (range, 46–72 years). A total of 70 brain metastases were treated, with each patient having between one and nine metastatic tumors. The mean tumor volume was 3.6 cm3 (range, 0.1–22.7 cm3). The mean peripheral dose was 16 Gy (range, 7–20 Gy), and the mean isodose curve was 54.6% (range, 45–80%).

At 12 months post-GKSRS, 68 metastatic tumors were assessed: 32 (47.1%) showed complete response, 20 (29.4%) had partial response, 14 (20.6%) remained stable, and two (2.9%) progressed, leading to a tumor control rate of 97.1%. No acute or chronic toxicity was observed.

GKSRS appears to be an effective and well-tolerated treatment for BMFOC, offering high tumor control rates and prolonged survival in selected patients.

Non-invasive vagus nerve stimulation (nVNS), including transcutaneous cervical (tcVNS) and auricular (taVNS) modalities, has garnered increasing attention as a neuromodulatory therapy for various neurological and psychiatric disorders. This narrative review synthesizes findings from over 80 studies, including randomized controlled trials, meta-analyses, and observational research published up to March 2024, evaluating nVNS in epilepsy, depression, stroke rehabilitation, headache, Parkinson’s disease, and Alzheimer’s disease. Evidence suggests that taVNS can reduce seizure frequency and improve quality of life in epilepsy. In major depressive disorder, nVNS demonstrates antidepressant effects comparable to pharmacotherapy, though the optimal stimulation parameters remain unclear. For post-stroke motor rehabilitation, both tcVNS and closed-loop stimulation systems enhance neuroplasticity and motor recovery. In Parkinson’s and Alzheimer’s diseases, preliminary findings indicate possible modulation of neuroinflammatory pathways and cognitive-motor functions, although recent meta-analyses report mixed efficacy. Challenges include methodological heterogeneity, protocol variability, and difficulties in designing effective sham controls, all of which limit the generalizability of current findings. Mechanistic differences between tcVNS and taVNS remain inadequately characterized. Overall, nVNS appears to be a safe and accessible therapeutic approach with broad clinical potential, particularly for treatment-resistant or underserved populations. However, future research must prioritize standardized protocols, robust clinical endpoints, and adequately powered trials to define efficacy and optimize treatment strategies. A greater focus on long-term outcomes, biomarker-guided personalization, and clinical significance over statistical findings will be critical in translating nVNS into routine practice.

Colorectal cancer (CRC) is a type of cancer that originates in the colon or rectum from precancerous polyps, which can evolve into cancerous growths over time. This review aimed to provide a comprehensive analysis of CRC, its subtypes, clinical manifestations, point-of-care diagnostic approaches, and management strategies. The clinical presentation of CRC often includes symptoms such as blood in stool, changes in bowel habits, abdominal discomfort, weight loss, fatigue, a feeling of incomplete bowel emptying, and anemia. The identification of these signs prompts healthcare professionals to initiate diagnostic measures without delay. Point-of-care diagnosis plays a pivotal role in the early detection of CRC, employing screening tests such as stool tests and colonoscopies. These diagnostic modalities enable healthcare professionals to identify precancerous polyps or early-stage tumors, facilitating timely intervention and significantly improving treatment outcomes. Adherence to screening guidelines is crucial for the prevention and early detection of CRC. Despite advancements in screening and treatment options, there remains a crucial need for more specific, minimally invasive screening methods with minimal side effects. By improving current detection methods, a better screening approach for CRC can be developed. Recent advancements, including single-cell sequencing, spatial transcriptomics, and artificial intelligence integration, hold great promise for enhancing early diagnosis and advancing personalized treatment strategies. Moreover, a healthy lifestyle, including a balanced diet, regular exercise, no tobacco use, and limited alcohol consumption, can significantly lower the risk of CRC. By emphasizing the importance of lifestyle modifications, early screening, and timely intervention, healthcare professionals can significantly reduce the burden of CRC and improve patient outcomes.