Zhihao Wang

Immune checkpoint inhibitors (ICIs) have revolutionized the oncological landscape by disrupting inhibitory pathways, notably programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) pathways, thereby reinvigorating host antitumor immunity. Although these agents have emerged as frontline standard therapies for malignancies, their clinical utility remains limited. Interpatient therapeutic variability is inextricably linked to the composition and functional capacity of the gut microbiome. The underlying mechanisms appear to involve a complex dialogue between the microbiota and host immune system, where microbial metabolites serve as critical mediators in remodeling the tumor microenvironment. Despite these insights, progression in the field remains constrained due to heterogeneity in study cohorts and sample-processing methodologies, hindering the establishment of reproducible individualized predictive models and clinical intervention strategies. Consequently, there is an urgent need to systematically delineate the microbiome–metabolite–immune axis to optimize the balance between ICI efficacy and systemic toxicity. By synthesizing the latest evidence, this review aimed to highlight the pivotal roles of specific taxa, including Bacteroides , Bifidobacterium , and Akkermansia muciniphila , in ICI efficacy. These microbes and their metabolic byproducts potentiate therapeutic responses by enhancing dendritic cell cross-presentation and promoting CD ⁸⁺ T-cell infiltration, often via activation of the cyclic GMP-AMP synthase-stimulator of interferon genes or nucleotide-binding oligomerization domain-containing protein 2 signaling pathways. Furthermore, these microbial components demonstrate the ability to protect the heart and colon against inflammation and barrier disruption, thereby mitigating immune-related adverse events. Although the feasibility and safety of interventions such as fecal microbiota transplantation and supplementation with next-generation encapsulated probiotics, postbiotics, or dietary fiber have been demonstrated in preclinical and Phase I trials, substantial hurdles remain. Future progress requires large-scale, multicenter, standardized, longitudinal studies integrating metagenomics and metabolomics to construct robust cross-cancer and cross-population predictive models. Such rigorous validation would enable the development of precise microbial interventions that maximize therapeutic gains while minimizing the incidence of adverse reactions.

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic inflammatory condition of the gastrointest

Arboviruses are a heterogeneous group of vector‐borne viruses from various viral families. The clinical manifestations associated with these viruses can vary from self‐limiting conditions to life‐threatening complications with haemorrhagic disorders. As a class of viruses with systemic infections, arboviruses can either directly or indirectly affect different parts of the body causing systemic complications such as cardiovascular diseases, coagulation dysfunctions, and various liver complications. The present review presents clinical, epidemiological, and mechanistic evidence describing liver involvement during acute arboviral infections, including those caused by Dengue Virus (DENV), Yellow Fever Virus (YFV), Zika Virus (ZIKV), and Chikungunya Virus (CHIKV). While much of the available data pertains to acute liver damage, such as H, hepatomegaly, or fulminant hepatitis, it also discusses the possibility that such acute injuries may, in certain cases, predispose to chronic liver inflammation and fibrosis. Although current direct evidence for long‐term hepatic sequelae is limited, this underexplored area may hold important clinical relevance in endemic settings. Therefore, this review emphasises the need for longitudinal research to establish whether arboviral infections pose a significant risk for chronic liver disease. Furthermore, it discusses the potential underlying mechanisms by which these viruses can induce hepatic disorders, including direct viral effects, immune‐caused complications, and interactions with various hepatic cells and components. Finally, this review addresses several future research directions to improve clinical outcomes of arbovirus‐caused liver complications.

Statins, widely recognized as a cornerstone in the prevention of cardiovascular diseases, have garnered increasing attention in oncology due to their pleiotropic effects, particularly their potential roles in regulating breast and colorectal cancer. Emerging evidence suggests that statins may exert anticancer effects through multiple mechanisms, including the mitochondrial apoptosis pathway, the LKB1-AMPK-p38MAPK-p53-survivin signaling cascade, inhibition of the mevalonate pathway, modulation of the EGFR/RhoA and IGF-1 signaling pathways, and regulation of the BMP/SMAD4 signaling pathway. However, significant heterogeneity exists in the reported anticancer effects of statins, likely due to variations in statin type (lipophilic vs hydrophilic), dosage, treatment duration, and population-specific characteristics. These factors contribute to inconsistencies in study outcomes. Additionally, while combination therapies incorporating statins with chemotherapy and immunotherapy have demonstrated synergistic effects in certain studies, their clinical utility remains to be fully established. Nevertheless, current evidence suggests that statins may have a potential role in reducing breast and colorectal cancer-related mortality. Future research should prioritize elucidating their precise molecular mechanisms, defining dose–response relationships, developing personalized treatment strategies within the framework of precision medicine, and validating their efficacy through large-scale, long-term prospective studies. These efforts will provide a more robust scientific foundation for the clinical application of statins in oncology. This review systematically explores the role of statins in breast and colorectal cancer regulation, covering clinical evidence, underlying biological mechanisms, pharmacological distinctions, synergistic therapeutic potential, and translational medicine prospects.

Delayed neuropsychiatric sequelae (DNS) significantly impact the quality of life in patients following acute carbon monoxide poisoning (COP). This systematic review and meta-analysis aimed to assess the relationship between serum neuron-specific enolase (NSE) levels at admission and the risk of DNS in adults after acute COP. Relevant observational studies with longitudinal follow-up were identified through searches in PubMed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure databases. The random-effects model was used to aggregate results, accounting for potential heterogeneity. Nine cohort studies, including 1501 patients, were analyzed, with 254 (16.9%) developing DNS during follow-up. The pooled data indicated that elevated serum NSE in the early phase was linked to a higher risk of subsequent DNS (odds ratio per 1 ng/mL increase in NSE: 1.10, 95% confidence interval: 1.06 to 1.15, P < 0.001). Moderate heterogeneity (I2 = 46%) among the studies was entirely attributed to one study with the longest follow-up duration (22.3 months; I2 = 0% after excluding this study). Subgroup analyses based on country, study design, sample size, age, sex, admission carboxyhemoglobin levels, DNS incidence, follow-up duration, and quality score yielded consistent results (P for subgroup differences all > 0.05). In summary, high serum NSE levels in the early phase of acute COP are associated with an increased risk of developing DNS during follow-up.

The present study aimed to investigate the distribution of T follicular helper (Tfh)-cell subsets in patients with hepatitis B virus (HBV) and determine the underlying mechanism of HBV regulation of Tfh cells. The frequency of peripheral blood Tfh subsets was analyzed using flow cytometry. The expression level of programmed cell death‑1 (PD‑1) and prostaglandin E2 (PGE2) was quantified using reverse transcription‑quantitative polymerase chain reaction and western blotting. The PGE2 level in culture supernatant was detected using enzyme‑linked immunosorbent assay. A Transwell chamber was used to co‑culture Tfh cells with HepG2 and HepG2.2.1.5. The percentage of inducible T‑cell costimulator (ICOS)+ and total Tfh cells was high at the immune activation (IA) group; however, it was reduced in the immune tolerance (IT), responders with HBsAg seroconversion (RP) and healthy control (HC) groups. The percentage of PD‑1+ Tfh cells was significantly higher in IA and IT compared with RP and HC. The ratio of PD‑1+/total Tfh cells was positively correlated with the load of HBV DNA; therefore, this ratio may act as an indicator for HBV replication. The expression level of PD‑1 in Tfh cells was higher in the HepG2.2.1.5 co‑cultured group compared with the HepG2 group, this may be due to the high PGE2 expression level in HBV‑infected HepG2.2.1.5 cells. The findings of the present study revealed an imbalanced distribution of PD‑1+ Tfh cells in patients with HBV at different immune phases. Additionally, HBV may upregulate the expression of PD‑1 in Tfh cells by promoting HepG2.2.1.5 to secret PGE2. Identifying the effect of HBV on Tfh‑cell subsets is crucial for improving immuno-based therapy for HBV.