Mediastinal germ cell tumors (GCTs) are rare malignant neoplasms that occasionally develop somatic-type malignancies (SMs), such as sarcomas, carcinomas, and hematologic malignancies.

We report a unique case of a 16-year-old male patient with a mediastinal GCT that simultaneously developed two different SMs: well-differentiated angiosarcoma and acute megakaryoblastic leukemia (AML). The patient initially presented with left shoulder pain and intermittent shortness of breath. The imaging study demonstrated a 12.5 × 9.0 × 8.5 cm heterogeneous mass in the left anterior mediastinum. The mediastinal mass was resected and showed a cystic mature teratoma with somatic transformation into well-differentiated angiosarcoma and AML. A subsequent bone marrow biopsy confirmed the diagnosis of AML, and next-generation sequencing demonstrated the presence of PTEN and TP53 gene mutations in the AML. Despite aggressive chemotherapy and allogeneic stem cell transplantation, the patient died 10 months after diagnosis.

Our report demonstrates the unique capability of mediastinal GCTs to simultaneously develop two different SMs. The presence of two different SMs in mediastinal GCTs is associated with extremely aggressive behavior and a poor prognosis.

Liver fibrosis is characterized by the excessive deposition of extracellular matrix, a process primarily driven by activated hepatic stellate cells (HSCs), and currently lacks effective therapy. Cathepsin K (CTSK) exhibits context-dependent roles across organ systems in fibrosis, but its function in liver fibrosis is unclear. This study aimed to investigate the role and underlying mechanisms of CTSK during liver fibrosis.

CTSK expression was analyzed in human fibrotic liver samples via transcriptomic analysis and confirmed in murine fibrosis models. The function of CTSK was investigated in both primary HSCs and LX-2 cells by assessing its effects on cell activation, proliferation, apoptosis, and the underlying signaling pathways following CTSK overexpression. The therapeutic potential was evaluated using an adeno-associated virus serotype 8 to overexpress CTSK in two etiologically distinct murine fibrosis models.

CTSK was upregulated in activated HSCs and fibrotic livers. Furthermore, we discovered that it mediates a negative feedback loop to inhibit the TGF-β/Smad pathway via Smad7/Smurf2-dependent TGF-β receptor-I degradation, thereby suppressing HSC activation and proliferation. CTSK also induced mitochondrial apoptosis through Bax/Bcl-2 imbalance and caspase-3 activation. Together, these actions contribute to the anti-fibrotic effect of CTSK. Notably, adeno-associated virus serotype 8-mediated CTSK overexpression attenuated liver fibrosis across multiple murine models.

Our study demonstrates that elevated CTSK functions as an endogenous protective factor that attenuates liver fibrosis. CTSK mediates negative feedback inhibition of the TGF-β pathway while concurrently promoting the mitochondrial apoptosis pathway. The dual anti-fibrotic mechanisms identify CTSK as a promising therapeutic target for liver fibrosis.

Chronic pancreatitis is an inflammatory disease and is difficult to manage despite advancements in medical science. This study examined the effect of water/ethanol extracts of Justicia carnea leaves on oxidative stress and glucagon expression in a mouse model of chronic pancreatitis induced by trinitrobenzenesulfonic acid (TNBS).

Twenty-five male Swiss albino mice were randomized and treated intrarectally with vehicle (the control group) or TNBS. Some TNBS-treated mice were treated orally with 200 mg/kg or 400 mg/kg J. carnea extracts, or with the positive control, 500 mg/kg sulfasalazine, every other day on three occasions. Oxidative stress markers and pancreatic glucagon expression were assessed.

Compared with the healthy control mice, treatment with TNBS significantly decreased the levels of pancreatic glutathione (0.89 µmol/g tissue vs. 7.16 µmol/g tissue in the control) and glutathione peroxidase activity, but significantly increased the levels of α-amylase and lipase activities, lipid peroxidation, total antioxidant capacity, and nitric oxide, as well as serum C-reactive protein (P < 0.05 for all), accompanied by severe inflammation and reduced glucagon expression in the pancreatic tissues. The toxic effects of TNBS were significantly mitigated by treatment with J. carnea extracts.

These findings provide evidence that treatment with J. carnea extracts inhibited oxidative stress and preserved glucagon expression in the pancreatic tissues of mice.

Hepatocellular carcinoma (HCC) is a malignant tumor with high incidence and mortality rates worldwide, in which immune evasion mechanisms play a crucial role in its progression and treatment. Natural killer group 2D ligands (NKG2DL), as key molecules activating immune cells, significantly influence the immune evasion of liver cancer through their regulatory mechanisms. This review summarizes the regulatory mechanisms of NKG2DL expression, including genetic, signaling pathway, non-coding RNA, and stress response modulation, and discusses their expression patterns and clinical relevance in HCC. Studies have shown that the expression status of NKG2DL not only impacts patient prognosis and therapeutic response but also provides potential targets for HCC immunotherapy. Future research should focus on the molecular networks regulating their expression and their synergy with immunotherapy to provide a theoretical basis for developing more precise diagnostic and personalized treatment strategies for HCC.

Acute liver failure (ALF) is a severe hepatic injury associated with high short-term mortality. Our previous study found that 1,5-anhydroglucitol (1,5AG) levels correlate with clinical outcomes in patients with liver failure. This study aimed to explore the potential effects and mechanisms of 1,5AG in ALF.

An experimental model of ALF was established using LPS and D-GalN. 1,5AG was administered to mice by gavage before modeling. Empagliflozin was then administered to reduce 1,5AG levels in mice. Peroxisome proliferator-activated receptor alpha (PPARα) agonists were also used to explore the role of 1,5AG in mice with liver failure.

1,5AG pretreatment significantly increased ALT and AST levels, aggravated histological damage and hepatocyte apoptosis, and increased mortality in ALF mice. Transcriptomic analysis and western blot validation revealed that 1,5AG significantly inhibited the PPARα signaling pathway and its downstream target, fibroblast growth factor 21. Empagliflozin treatment reduced 1,5AG levels, alleviated liver injury and hepatocyte apoptosis, and promoted the PPARα signaling pathway in ALF. PPARα agonists effectively reversed the effects of 1,5AG on ALF, thereby alleviating liver damage, pathological injury, and hepatocyte apoptosis.

1,5AG exacerbated liver injury in ALF mice by inhibiting the hepatic PPARα pathway, thereby promoting hepatocyte apoptosis.

The long-term clinical outcomes of patients with hepatitis B virus (HBV)-related cirrhosis receiving nucleos(t)ide analog (NA) therapy according to virological response patterns remain inadequately defined. This study aimed to investigate the association between virological response patterns and clinical outcomes in a large, long-term, real-world cohort.

This retrospective–prospective cohort study enrolled patients with HBV-related cirrhosis receiving NA therapy from 2009 to 2019. According to the serum HBV DNA levels during the initial two years of antiviral treatment, patients were categorized as having a complete (CVR) or partial virological response (PVR). Patients with CVR were further stratified according to their dynamic HBV DNA changes during follow-up into maintained virological response (MVR) or virological breakthrough (VBT) patterns. The primary clinical outcomes included hepatocellular carcinoma (HCC), acute-on-chronic liver failure, and liver-related death. Secondary endpoints included recompensation and progression to decompensation. Cox proportional hazards regression was used to assess the association between virological response patterns and clinical endpoints.

In total, 1,869 patients were enrolled. During a median follow-up of seven years, the MVR, VBT, and PVR rates were 65.4%, 26.5%, and 8.1%, respectively. The cumulative serum hepatitis B surface antigen (HBsAg) clearance rate was 9.8%. Moreover, 34.9% of patients with HBsAg < 100 IU/mL at baseline experienced HBsAg clearance. Compared with patients with VBT and PVR, those with MVR had a lower five- and ten-year cumulative incidence of HCC in both the compensated (five-year: 10.1% vs. 17.0%; ten-year: 14.2% vs. 33.6%; P < 0.001) and decompensated cirrhosis subgroups (five-year: 19.5% vs. 36.7%; ten-year: 25.7% vs. 49.7%; P < 0.001). Similarly, patients with MVR also had a lower cumulative incidence of liver-related death. Additionally, a higher hepatic recompensation rate was observed in patients with MVR than in those with VBT (34.1% vs. 22.5%, P < 0.001). Importantly, patients achieving HBsAg clearance and undetectable serum HBV DNA levels (“functional cure” during ongoing NA therapy) had the lowest five- and ten-year cumulative incidence of HCC (3.9% and 8.7%, respectively).

Patients with long-term MVR exhibited a lower incidence of HCC and liver-related death in both compensated and decompensated HBV-related cirrhosis subgroups, especially those achieving “functional cure.” However, more than 30% of patients experienced PVR or VBT during long-term NA antiviral therapy. These findings highlight the importance of long-term, rigorous monitoring after initial CVR to optimize outcomes and support clinical decision-making.

Extrahepatic cancers have been recognized as a significant outcome of metabolic dysfunction–associated steatotic liver disease (MASLD), which involves five cardiometabolic risk factors, including hypertension, and is associated with the tumorigenesis of several cancers or with anti-cancer treatment. We aimed to investigate the association between hypertension, liver fibrosis, and extrahepatic cancers in the MASLD population.

This multicenter cross-sectional study was based on a MASLD population from hospital-based databases across 11 centers nationwide in China, according to MASLD diagnostic criteria identified using keywords and ICD-10 codes. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between risk factors and extrahepatic cancers.

A total of 103,652 individuals with MASLD were identified, among whom 6,605 were diagnosed with extrahepatic cancers. The primary outcome revealed that hypertension was significantly associated with extrahepatic cancers (OR 1.14, 95% CI: 1.08–1.21), and its combination with hyperglycemia further increased this association (OR 1.36, 95% CI: 1.22–1.51). Risk factors for extrahepatic cancers included being over 40 years of age and female sex. Conversely, certain metabolism-based treatments were found to have potentially protective effects, including angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, fibrates, GLP-1 receptor agonists, and thiazolidinediones. After adjusting for confounding factors, the fibrosis-4 (FIB-4) score was associated with extrahepatic cancers. In the hypertension subgroup, FIB-4 scores of 1.30–2.66, 2.67–3.47, and ≥ 3.48 were associated with extrahepatic cancers in individuals aged 35–64 years, consistent with findings in those aged ≥ 65 years of age with FIB-4 ≥ 2.

Hypertension combined with liver fibrosis is associated with extrahepatic cancers in patients with MASLD.

Hepatic ischemia–reperfusion (HIR) injury impairs outcomes post–liver transplantation. Therefore, we aimed to investigate the role and mechanism of miR-381-3p in HIR.

The study enrolled 150 healthy controls, 82 non-HIR-injured patients, and 68 patients with HIR injury following liver transplantation. Clinical data were analyzed. Multivariate analysis identified HIR risk factors; the predictive value of miR-381-3p was assessed via receiver operating characteristic analysis. An in vitro hypoxia/reoxygenation (H/R) model was established and employed. The cellular effects of miR-381-3p and JAK2 were evaluated using CCK-8, flow cytometry, ELISA, luciferase, RIP, and bioinformatics.

Serum miR-381-3p was significantly elevated in HIR compared with the other groups. miR-381-3p was the strongest independent HIR risk factor, which was confirmed by receiver operating characteristic analysis. H/R upregulated miR-381-3p. Inhibiting miR-381-3p counteracted H/R-induced decreased viability and increased apoptosis, inflammation, and oxidative stress. miR-381-3p directly bound to and suppressed JAK2 via its 3′ untranslated region (validated by luciferase and RIP). Transfection of si-JAK2 abolished the protective effects of miR-381-3p inhibition.

miR-381-3p exacerbates post-transplant HIR by directly targeting JAK2, amplifying inflammation and oxidative stress. Thus, our findings nominate serum miR-381-3p as a promising non-invasive biomarker and suggest its potential as a therapeutic target for mitigating HIR injury.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has become one of the leading causes of chronic liver diseases in China, imposing a substantial and growing burden on the healthcare system. Considering the large number of individuals affected by MAFLD and the gap in disease management capacity at the primary care level, standardized guidance tailored to primary healthcare settings is urgently needed. In response, the Chronic Disease Management Branch of the China Medical Biotechnology Association convened a multidisciplinary working group incorporating hepatologists, general practitioners, and other specialists to initiate the first China national Guidelines for Diagnosis and Management of Metabolic Dysfunction-associated Fatty Liver Disease in Primary Care (2025). These guidelines provide recommendations and suggestions covering screening, risk assessment, diagnosis, treatment, referral pathways, and follow-up tailored for primary care institutions, thereby improving the long-term outcomes for the population with MAFLD and comprehensively strengthening the role of primary healthcare in chronic liver disease management.