Information on the survival of urothelial cancer (UCa) patients with brain metastases (BM) is largely unreliable due to the rarity of such cases. Previous studies that have attempted to capture the prevalence and survival of these patients are limited to case series and retrospective studies with small cohort sizes. This study aimed to explore patient characteristics and treatment outcomes based on treatment modalities from a large sample of patients with UCa and BM.

In this retrospective study, we utilized the TriNetX Research Network, a real-world and in-house database with longitudinal electronic medical records from 92 institutions. The database was queried for patients with UCa who also had BM. Kaplan–Meier plots were used to assess overall survival (OS). Log-rank tests were applied for stratified outcomes. The Cox proportional hazards model was used for continuous data.

We identified 357 patients with UCa and BM, representing 4.7% of the 7,521 patients diagnosed with primary UCa. The mean age at diagnosis was 65.6 years, with a predominance of male patients (67%). The median OS from BM diagnosis was 18.6 months. For patients treated solely with stereotactic radiosurgery (SRS), the median OS was 20.8 months. For those treated with both SRS and surgical resection, the median OS was 18.6 months. There was no significant difference in survival between patients treated with SRS alone and those treated with both SRS and surgical resection (p = 0.875). For patients treated only with gemcitabine chemotherapy, the median OS was 15.4 months.

This study represents the largest known retrospective analysis of UCa patients with BM. Survival trends for patients treated with surgical resection, SRS, and systemic therapies are described in detail.

Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory condition affecting the ileum, colon, and rectum, including ulcerative colitis and Crohn’s disease. Clinical symptoms include abdominal pain, diarrhea, and even bloody stools. The intestinal barrier is the first line of defense between the intestinal tract and the external environment, and maintaining its stability is essential for intestinal health. On one hand, it enables the digestion and absorption of water and nutrients; on the other, it plays a crucial role in reducing the absorption of toxins and the invasion of pathogens. Damage to the intestinal barrier has become one of the most important factors in the onset and progression of IBD. However, there is currently no literature that systematically reviews the mechanisms of the intestinal barrier in the pathogenesis of IBD and the factors influencing it. In this paper, we aimed to systematically elaborate on the role of the intestinal barrier in IBD through the perspectives of oxidative stress, intestinal flora, and cellular autophagy. Our goal was to explore the mechanisms of the intestinal barrier in IBD more deeply and to provide new insights for the diagnosis and treatment of IBD. This article will summarize the composition of the intestinal barrier, the factors affecting it, and strategies to protect it.

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.

Metabolic dysfunction-associated steatotic liver disease has emerged as a leading cause of chronic liver disease and cirrhosis in the Western world. With rising rates of obesity, the prevalence of metabolic dysfunction-associated steatohepatitis (MASH)-related cirrhosis is expected to increase. MASH is associated with chronic hepatic inflammation and progressive liver fibrosis, and significant research is focused on developing pharmacological therapies to reverse these downstream complications. Recent trials have explored various therapeutic targets across metabolic, inflammatory, and fibrogenic pathways aimed at decreasing liver triglycerides, inflammation, lipotoxicity, and fibrosis. Some of these drugs show promise in reversing biomarkers and/or histologic markers of steatohepatitis and fibrosis, although most have been primarily studied in non-cirrhotic patients. However, in the context of the significant unmet medical need of patients with MASH-associated cirrhosis, growing interest in targeting compensated cirrhosis has prompted renewed investment in numerous early clinical and late-stage programs evaluating novel investigational agents in this population. This review summarizes current therapies under evaluation in phase 2 and 3 clinical trials for MASH-related cirrhosis, highlighting drug mechanisms, outcomes, and future research directions.

The diagnostic value of primary biliary cholangitis (PBC)-specific antibodies in patients with elevated alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels, and other identifiable causes, was unclear. Our study aimed to determine whether etiological treatments in PBC-specific antibody-positive patients could improve liver biochemical tests, thereby distinguishing them from individuals with PBC.

We enrolled patients who were positive for PBC-specific antibodies and elevated ALP and/or GGT levels but with other identifiable etiologies. Changes in liver biochemistry following non-ursodeoxycholic acid etiological treatments were monitored.

A total of 155 patients with positive PBC-specific antibodies and elevated ALP and/or GGT levels due to non-PBC diseases were enrolled. Among them, 100 patients were diagnosed with non-PBC liver diseases, mainly metabolic-associated fatty liver disease, drug-induced liver injury, and autoimmune hepatitis. Additionally, 55 patients had non-liver diseases, predominantly connective tissue diseases. The median follow-up duration was 15.9 (4.7–25.6) months. Among 141 patients who completed follow-up after receiving etiological treatments, 85.1% (120/141) showed improvement in ALP and/or GGT levels, with 51.8% (73/141) achieving normalization of both ALP and GGT. However, 68 patients continued to exhibit elevated ALP and/or GGT, with 55 patients displaying isolated GGT elevation and 11 patients showing liver histological changes not consistent with PBC.

PBC-specific antibodies, along with elevated ALP and GGT levels, may occur in various non-PBC diseases. Etiological treatments may improve or even resolve cholestatic biochemistry. For these patients, initiating etiological treatment rather than immediately starting ursodeoxycholic acid therapy would be justified.

China has made remarkable progress in controlling chronic hepatitis B virus (HBV) infection over the past three decades. The prevalence of hepatitis B surface antigen has declined from 9.72% in 1992 to 5.86% in 2020, with a striking reduction from 9.67% to 0.30% among children under five. Universal hepatitis B vaccination has been pivotal, preventing more than 40 million infections and seven million HBV-related deaths since 1992. Nevertheless, an estimated 75 million individuals are currently living with chronic HBV infection in China. Among them, only 59.78% are aware of their infection status, and about 30 million remain undiagnosed. Of those diagnosed, 38.25% (approximately 17 million) meet the criteria for antiviral treatment, yet only 17.33% (about three million) are receiving treatment. To accelerate progress toward the World Health Organization’s elimination targets, China has updated its clinical guidelines to expand treatment eligibility and improve diagnosis and treatment coverage. Moreover, Chinese pharmaceutical companies and academic institutions are actively engaged in developing novel therapies with promising efficacy, aiming to achieve a functional cure. China’s holistic approach, combining evidence-based public health interventions with active clinical management and innovative pharmaceutical development, provides valuable experience for global HBV elimination initiatives. This review aimed to summarize China's progress in HBV control, identify remaining gaps in diagnosis and treatment, and highlight strategic approaches, including public health interventions, clinical policy updates, and pharmaceutical innovation, toward achieving HBV elimination.

T-cell receptor (TCR) sequencing provides a novel platform for insight into and characterization of intricate T-cell profiles, advancing the understanding of tumor immune heterogeneity. Recently, transarterial chemoembolization (TACE) combined with systemic therapy has become the recommended regimen for advanced hepatocellular carcinoma. The regulation of the immune microenvironment after TACE and its impact on tumor progression and recurrence has been a focus of research. By examining and tracking fluctuations in the TCR repertoire following combination treatment, novel perspectives on the modulation of the tumor microenvironment post-TACE and the underlying mechanisms governing tumor progression and recurrence can be gained. Clarifying the distinctive metrics and dynamic alterations of the TCR repertoire within the context of combination therapy is imperative for understanding the mechanisms of anti-tumor immunity, assessing efficacy, exploiting novel treatments, and further advancing precision oncology in the treatment of hepatocellular carcinoma. In this review, we initially summarized the fundamental characteristics of TCR repertoire and depicted immune microenvironment remodeling after TACE. Ultimately, we illustrated the prospective applications of TCR repertoires in TACE combined with systemic therapy.

Liver failure encompasses a range of severe clinical syndromes resulting from the deterioration of liver function, triggered by factors both within and outside the liver. While the definition of acute-on-chronic liver failure (ACLF) may vary by region, it is universally recognized for its association with multiorgan failure, a robust inflammatory response, and high short-term mortality rates. Recent advances in metabolomics have provided insights into energy metabolism and metabolite alterations specific to ACLF. Additionally, immunometabolism is increasingly acknowledged as a pivotal mechanism in regulating immune cell functions. Therefore, understanding the energy metabolism pathways involved in ACLF and investigating how metabolite imbalances affect immune cell functionality are crucial for developing effective treatment strategies for ACLF. This review methodically examined the immune and metabolic states of ACLF patients and elucidated how alterations in metabolites impact immune functions, offering novel perspectives for immune regulation and therapeutic management of liver failure.

The performance of neurodegenerative biomarkers—neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1)—in diagnosing minimal hepatic encephalopathy (MHE) has not been systematically evaluated, simultaneously, nor have their associations with the development of overt hepatic encephalopathy (OHE). This study aimed to evaluate the performance of plasma NfL, GFAP, tau, and UCHL1 in diagnosing MHE and predicting the development of OHE in Chinese patients with hepatic cirrhosis.

In this prospective study, 124 patients with hepatic cirrhosis were recruited. The Psychometric Hepatic Encephalopathy Score was used to diagnose MHE, and OHE development was observed during a 30-day follow-up period. Plasma levels of NfL, GFAP, tau, and UCHL1 were measured using the highly sensitive single-molecule array when MHE was diagnosed. Additionally, serum interleukin-6 (IL-6) levels and the model for end-stage liver disease (MELD) and MELD-Na scores were also measured.

MHE was diagnosed in 57 (46.0%) patients. Patients with MHE had significantly higher plasma levels of NfL and GFAP (34.2 vs. 22.4 pg/mL and 173 vs. 97.6 pg/mL, respectively; both p < 0.001) and lower tau levels (8.4 vs. 11.6 pg/mL, p = 0.048) compared to those without MHE. Plasma NfL (odds ratios = 1.027, 95% confidence interval [CI]: 1.006–1.048; p = 0.013) and serum ammonia levels (odds ratios = 1.021, 95% CI: 1.006–1.036; p = 0.007) were independently associated with MHE occurrence. A combination of NfL, GFAP, tau, and UCHL1 was effective in diagnosing MHE in all cirrhotic patients (area under the receiver operating characteristic curve [hereinafter referred to as AUROC]: 0.748, 95% CI: 0.662–0.821), with an accuracy, sensitivity, and specificity of 71.0%, 71.9%, and 71.6%, respectively. In patients without previous OHE, the combination had an AUROC of 0.764 (95% CI: 0.673–0.840), with an accuracy, sensitivity, and specificity of 72.5%, 71.7%, and 73.0%, respectively. Furthermore, GFAP (hazard ratio (HR) = 1.003, 95% CI: 1.000–1.005; p = 0.044), IL-6 (HR = 1.003, 95% CI: 1.001–1.004; p < 0.001), and MELD score (HR = 1.139, 95% CI: 1.072–1.210; p < 0.001)—but not NfL, tau, and UCHL1—were identified as risk factors for 30-day OHE development.

The combination of plasma levels of NfL, GFAP, tau, and UCHL1 performs well in diagnosing MHE. Additionally, MELD score, IL-6, and GFAP appear to be significant predictors of OHE development in patients with hepatic cirrhosis.