Despite the large number of cancer chemotherapeutics, cancer treatment is still not very satisfactory. Immune checkpoint inhibition has emerged as a new ray of hope in the immunotherapy approach for cancer treatment. Immune checkpoint inhibitors are molecules located on the surface of immune cells that regulate unnecessary immune responses and keep autoimmune reactions in check. Immune checkpoint inhibitors (ICIs), such as anti-programmed cell death protein-1 and anti-programmed cell death ligand-1, have been employed to activate receptors on immune cells like T-cells, which can deactivate the immune checkpoint and thus reactivate them against cancer cells. However, ICI therapy has limitations, including resistance development in patients, its suitability for all patients, multiple organ disorders, and hyper-progression. Therefore, understanding the chemical structures of small molecule ICIs may aid in designing and developing novel ICIs with improved efficacy and efficiency for cancer chemotherapy. This review’s novelty lies in its summary of the U.S. Food and Drug Administration-approved drugs, repurposed drugs, candidate drugs used alone or in combination with monoclonal antibodies, and novel potential lead molecules under preclinical investigation, which may be useful for designing new chemical entities as ICIs. The review describes 10 different drugs approved by the U.S. Food and Drug Administration that have demonstrated immune checkpoint inhibition targeting the programmed cell death ligand-1/programmed cell death protein-1 signaling, CTLA-4/CD28, TIGIT/PVR, and CD47/SIRPα pathways, as well as three repurposed drugs, 11 candidate drugs, and nine drugs in combination with monoclonal antibodies that are in various phases of clinical trials.

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.

The incidence of cardia gastric cancer (CGC) is rising worldwide, particularly in East Asia. There has been a debate over whether Helicobacter pylori (H. pylori) constitutes a risk factor for CGC. This study aimed to evaluate the relative risk of H. pylori infection and CGC in Asian countries.

Relevant studies examining H. pylori and CGC were searched in PubMed, Embase, and Web of Science from their inception to June 30, 2024. Either a random-effect model or a fixed-effect model was used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs). Sensitivity analyses and assessments of publication bias were performed. The stability of results was evaluated in cases where publication bias was detected.

A total of 24 studies were included in the meta-analysis. A significant association between H. pylori and CGC was observed (OR = 2.20, 95% CI 1.73–2.80). In a subgroup analysis of different countries, a significant association was observed in East Asian countries, including China (OR = 2.12, 95% CI 1.63–2.77), Japan (OR = 2.21, 95% CI 1.16–4.20), and Korea (OR = 2.36, 95% CI 1.58–3.54), but not in Iran (OR = 1.48, 95% CI 0.77–2.84). The pooled OR from five prospective cohort studies revealed a strong association between H. pylori and CGC (OR = 2.32, 95% CI 1.47–3.66).

East Asia bears a significant burden of H. pylori-related CGC. A clear association between H. pylori infection and CGC was observed in this region.

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.

Thrombocytopenia in cirrhosis presents significant challenges in clinical practice. To help clinicians rapidly understand and standardize the diagnosis and treatment of this condition, the Liver Fibrosis, Cirrhosis, and Portal Hypertension Group under the Chinese Society of Hepatology, Chinese Medical Association, convened experts across relevant fields to formulate the Expert Consensus for the Management of Thrombocytopenia in Cirrhosis. This consensus aimed to provide evidence-based guidance for clinical diagnosis and treatment.

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.

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.

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.

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.