Background Ubiquitination plays a significant role in biological processes and regulates the tumor microenvironment (TME). Tripartite Motif Containing 54 (TRIM54) is an E3 ubiquitin ligase that, in recent years, has been shown to control the development of certain malignancies. However, the expression and function of TRIM54 across pan-cancer and its role in the TME remain unclear. Methods Data from the public databases were utilized to explore the expression, prognostic value, clinical features, enrichment analysis, and genetic alterations of TRIM54 in tumors. Associations between TRIM54 expression and immune cell infiltration (ICI), immunotherapy response, and targeted drugs were analyzed using bioinformatics. Results Compared with normal tissues, TRIM54 is aberrantly expressed across a diverse range of malignancies. The expression of TRIM54 could predict diagnosis and prognosis across most cancer types. The enrichment analysis showed that TRIM54 and its related proteins were closely associated with ubiquitination modification and tumor-associated pathways. In addition, TRIM54 was tightly associated with ICI and immunotherapy. Finally, we screened out several targeted drugs that could regulate TRIM54 expression during immunotherapeutic responses. Conclusion TRIM54 plays a vital part in pan-cancer development, and its aberrant expression in tumors may be associated with ICI in TME. At the same time, TRIM54 has strong prognostic predictive ability and is a promising predictive biomarker for immunotherapy.

Hepatocellular carcinoma (HCC), a highly lethal disease often developing in the context of chronic liver disease, is marked by high relapse rates and low 5-year survival. To investigate the multicellular ecosystem and molecular features of hepatocarcinogenesis and progression, a comprehensive analysis integrating single-cell and spatial transcriptomics was conducted. Significant alterations were observed in various cell types, notably an increase in liver parenchymal and endothelial cells, which play critical roles in tissue repair and angiogenesis. Scissor + cells, predominantly hepatocytes, were identified as potentially evolving into malignant cells with poor prognosis and enhanced immune evasion capabilities. Key genes associated with Scissor + cells exhibited potential as cancer prognostic markers. Additionally, the disruption of cellular communication networks during malignant progression revealed the evolution of hepatocytes into cancerous phenotypes. The enhanced signaling pathways, such as MDK-SDC4 and COL4A-SDC, were identified as pivotal in driving the malignant transformation of hepatocytes. This transformative process, wherein Scissor + cells acquire malignant features, highlights novel mechanisms of cancer progression. These findings provide deeper insights into hepatocarcinogenesis and offer potential avenues for targeted and personalized therapeutic strategies.

Introduction: This study systematically evaluates the clinical efficacy and safety of acupuncture in the treatment of paralytic strabismus. Methods: A comprehensive literature search was conducted across PUBMED, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), SINOMED, Wanfang Data, and VIP databases from inception to July 30, 2025. Eligible studies were screened, extracted, and assessed for quality. Meta-analysis was performed using RevMan 5.3, and trial sequential analysis (TSA) was conducted using TSA v0.9. Results: Fifteen randomized controlled trials (RCTs) were included. Meta-analysis revealed that the acupuncture group demonstrated superior clinical efficacy compared to controls [RR = 1.19, 95% CI (1.08, 1.30), P = 0.0003], with significantly shorter recovery time [MD = -17.10, 95% CI (-26.76, -7.43), P = 0.0005], greater improvement in diplopia [MD = -4.43, 95% CI (-5.40, -3.46), P < 0.00001], and reduced strabismus angle [MD = -5.16, 95% CI (-7.06, -3.26), P < 0.00001]. TSA further confirmed the robustness of acupuncture’s therapeutic effect. Conclusion: Acupuncture appears to be a safe and effective intervention for paralytic strabismus. This meta-analysis was registered with the International Prospective Register of Systematic Reviews (PROSPERO; Registration No. CRD42025637328)

BACKGROUND:Metabolic-associated fatty liver disease (MAFLD) is a prevalent chronic liver condition globally, characterized by suboptimal treatment outcomes. Traditional therapies often fail to address the multifaceted pathogenesis of MAFLD, which involves lipid metabolism, inflammation, and gut-liver axis dysregulation. JiGuCao Capsule formula (JCF), a patented Chinese medicine, has demonstrated clinical efficacy in liver disease treatment, indicating its potential as a new therapeutic option for MAFLD. PURPOSE:This study aimed to investigate the therapeutic effects and underlying mechanisms of JCF in treating MAFLD, particularly focusing on its impact on liver pathology, intestinal health, and gut microbiota composition. METHODS:A MAFLD mouse model was developed by administering a high-fat diet and 5% fructose water for 16 weeks. At week 8, mice exhibited significant steatosis, inflammation, and insulin resistance. Fifty mice were allocated into two groups: the normal diet (ND) group with 19 mice and the high-fat feed diet (HFD) group with 31 mice. Seven mice from each group were sacrificed at week 8 for serological and histopathological assessments. The remaining mice were allocated into ND (n = 6), HFD (n = 6), HFD + JCFL (human equivalent dose,780 mg/kg, n = 6), HFD + JCFH (threefold the human equivalent dose, 2340 mg/kg, n = 6), HFD + Polyene Phosphatidylcholine (PPC) (human equivalent dose,177.84 mg/kg, n = 6) and ND+ JCF (human equivalent dose,780 mg/kg, n = 6) groups. Daily gavage started at week 9. At week 16, after fasting, body weight and liver condition were recorded, and mice were euthanized with pentobarbital sodium. Mouse tissues and feces were collected for histopathological, molecular biological, and multi-omics analyses. RESULTS:JCF effectively slowed MAFLD progression in mice by decreasing hepatic lipid accumulation and inflammation. Treatment with JCF significantly reduced hepatic triglycerides and inflammatory markers, including TNF-α and IL-6. JCF enhanced lipid metabolism, repaired the intestinal barrier, and lowered inflammatory cytokines in the intestines, as indicated by reduced serum LPS and restored tight junction proteins expression, such as claudin-1 and occludin. Fecal microbiota analysis indicated that JCF treatment elevated Lactobacillus levels and reduced Colidextribacter levels, correlating with enhanced metabolic profiles. The primary bioactive compounds identified in JCF responsible for these therapeutic effects were betulinic acid, cholic acid, deoxycholic acid, oleanolic acid, and pectolinarigenin. Transcriptomic analysis showed that JCF regulated key pathways involved in lipid metabolism, including the pparγ-cd36 axis and modulation of ox-LDL levels. The results indicate that JCF effectively mitigates MAFLD by influencing the gut-liver axis and lipid metabolism. CONCLUSION:JCF alleviates MAFLD by modulating the gut-liver axis and lipid metabolism. Its effects involve improving gut barrier function, regulating microbiota, and targeting the pparγ-cd36 axis. Active compounds like betulinic acid support its therapeutic potential. JCF shows promise as a novel treatment for MAFLD, with further clinical studies needed.

ABSTRACT Aims The TiaoGanXiaoZhi formula (TGXZ), a traditional Chinese medicine, has been shown to alleviate the progression of metabolic‐associated fatty liver disease (MAFLD) clinically. However, its underlying mechanism remains unclear. This study aimed to investigate the effects and mechanisms of TGXZ in treating MAFLD in mouse models. Methods The MAFLD mouse model was established using a high‐fat diet and 5% fructose water over 16 weeks. At Week 8, mice exhibited significant steatosis, inflammation, and insulin resistance. A total of 42 mice were divided into the normal feed diet (NFD) group (n = 18) and the high‐fat feed diet (HFD) group (n = 24). Six mice from each group were killed at Week 8 for serological and histopathological assessments. The remaining mice were allocated into NFD (n = 6), HFD (n = 6), HFD + TGXZ (n = 6), NFD + TGXZ (n = 6), and HFD + Placebo (n = 6) groups. TGXZ (or placebo) was administered at a clinical equivalent dose of 7.699 g/(kg·d) to the respective groups, while NFD and HFD groups received distilled water. Daily gavage started in Week 9. At Week 16, after fasting, body weight and liver condition were recorded, and mice were euthanized with pentobarbital sodium. Liver tissue was collected for further analysis, and the remaining tissue and feces were stored at −80°C. Data were graphed using GraphPad Prism 8.0.0 and analyzed with SPSS Statistics 25.0. Results are expressed as mean ± standard deviation. Statistical comparisons were made using Student's t‐test for two groups and one‐way ANOVA for more than two groups, with significance set at p < 0.05. Results Compared to the MAFLD mouse model group, TGXZ treatment significantly downregulated the weight of white adipose tissue (1.61 ± 0.66 vs. 3.06 ± 0.34 g, p < 0.0010), liver weight (1.22 ± 0.16 vs. 1.98 ± 0.39 g, p = 0.0031), and the levels of alanine aminotransferase (20.6 ± 3.4 vs. 46.1 ± 12.3 U/L, p < 0.0010), aspartate aminotransferase (99.9 ± 19.1 vs. 168.4 ± 34.3 U/L, p = 0.0014), cholesterol (2.95 ± 0.56 vs. 4.38 ± 0.34 mmol/L, p = 0.0053), triglycerides (2.25 ± 0.41 vs. 4.18 ± 0.67 mmol/L, p < 0.0010), low‐density lipoprotein (0.66 ± 0.11 vs. 1.41 ± 0.52 mmol/L, p = 0.0073), and total bile acid (0.71 ± 0.41 vs. 2.18 ± 0.61 mmol/L, p = 0.0017), except for high‐density lipoprotein (2.41 ± 0.81 vs. 2.55 ± 0.31 mmol/L, p = 0.5655). The liver transcriptome, fecal microbiota sequencing, and fecal lipidomics analysis demonstrated that TGXZ treatment improved the expression of genes related to lipid metabolism, alleviated intestinal microbiota disorders, and mitigated lipid disturbances caused by MAFLD. Conclusions Our study demonstrated that TGXZ treatment effectively alleviated the progression of MAFLD. The inhibitory effects of TGXZ on MAFLD may be attributed to its regulation of gut microbiota, lipid metabolism, and hepatic inflammation.

Hepatocellular carcinoma (HCC) represents a malignant tumor that poses a significant threat to human health, and its occurrence and development are a complex multi-stage process. This review delineates the critical factors implicated in the transition from normal hepatocytes to malignant liver cells, encompassing dysregulated signalling pathways, key oncogenes, associated non-coding RNAs (ncRNAs), molecular alterations within the cellular microenvironment, spatial transcriptomic profiling, and advancements in anticancer therapies, thereby offering a comprehensive reference for elucidating HCC pathogenesis and formulating more targeted therapeutic approaches. Additionally, diagnostic and therapeutic aspects of liver diseases are examined, including the identification of diagnostic biomarkers, the development of therapeutic modalities, and recent innovations in pharmacological interventions, thereby providing novel insights into liver disease progression and insights into the development of novel therapeutic strategies.

Objective To investigate the biological characteristics and clinical relevance of CHAC1 in bladder urothelial carcinoma(BLCA).Methods The original data of CHAC1 was obtained from the Cancer Genome Atlas and the Human Protein At-las.R software,MEXPRESS platform and TISIDB platform were used for gene expression analysis,survival analysis,copy number variation and methylation analysis,gene enrichment analysis and immune infiltration analysis of CHAC1.Results Compared with normal tissues,CHAC1 is abnormally expressed in a variety of tumor tissues(P＜0.05),especially in BLCA(P＜0.001).High expression of CHAC1 predicts poor prognosis of BLCA,which is related to CHAC1 hypomethylation level.CHAC1 enrichment analy-sis showed that it was involved in a variety of metabolism-related biological processes,including amino acid metabolism and GSH me-tabolism.The expression level of CHAC1 in BLCA was associated with excessive infiltration of a variety of immune cells,including dendritic cells,activated dendritic cells,neutrophils,macrophages,regulatory T cells,Th1 cells,Th2 cells,B cells,and NK CD56dim cells.Conclusion CHAC1 may become a potential biomarker and therapeutic target for evaluating BLCA prognosis and modulating levels of immune infiltration.

Hepatocellular carcinoma (HCC), one of the leading causes of cancer‑related mortality worldwide, is challenging to identify in its early stages and prone to metastasis, and the prognosis of patients with this disease is poor. Treatment options for HCC are limited, with even radical treatments being associated with a risk of recurrence or transformation in the short term. Furthermore, the multi‑tyrosine kinase inhibitors approved for first‑line therapy have marked drawbacks, including drug resistance and side effects. The rise and breakthrough of immune checkpoint inhibitors (ICIs) have provided a novel direction for HCC immunotherapy but these have the drawback of low response rates. Since avoiding apoptosis is a universal feature of cancer, the induction of non‑apoptotic regulatory cell death (NARCD) is a novel strategy for HCC immunotherapy. At present, NARCD pathways, including ferroptosis, pyroptosis and necroptosis, are novel potential forms of immunogenic cell death, which have synergistic effects with antitumor immunity, transforming immune 'cold' tumors into immune 'hot' tumors and exerting antitumor effects. Therefore, these pathways may be targeted as a novel treatment strategy for HCC. In the present review, the roles of ferroptosis, pyroptosis and necroptosis in antitumor immunity in HCC are discussed, and the relevant targets and signaling pathways, and the current status of combined therapy with ICIs are summarized. The prospects of targeting ferroptosis, pyroptosis and necroptosis in HCC immunotherapy are also considered.

Men are inevitably plagued by prostate disease throughout their lives. However, the understanding of the pathogenesis of prostate diseases is still limited. In the 1960s, McNeal proposed the theory of prostate zones: the prostate was divided into three main zones: transition zone, central zone, and peripheral zone. Over the past 50 years, significant differences between different prostate zones have been gradually revealed. We summarized the most significant differences in different zones of the prostate. For the first time, we proposed the “apparent difference in prostate zones” concept. This new concept has been proposed to understand the different zones of the prostate better. It also provided new ideas for exploring the susceptibility of lesions in different prostate zones. Despite the reported differences between zones, the treatment of prostate-related diseases remains partition agnostic. Therefore, we also discussed the clinical significance of the “apparent difference in the prostate zone” and emphasized the necessity of prostate zones.

Purpose: ST6 Beta-Galactoside Alpha-2,6-Sialyltransferase 2 (ST6GAL2), a member of the sialic acid transferase family, is differentially expressed in diverse cancers. However, it remains poorly understood in tumorigenesis and impacts on immune cell Patients and Methods: Herein, the expression, diagnosis, prognosis, functional enrichment, genetic alterations, immune characteristics, and targeted drugs of ST6GAL2 in HCC were researched by conducting bioinformatics analysis, in vivo, and in vitro experiments. Results: ST6GAL2 was remarkably decreased in HCC compared to non-tumor tissues, portending a poor prognosis associated with high DNA methylation levels. Functional enrichment and GSVA analyses revealed that ST6GAL2 might function through the extracellular matrix, PI3K-Akt signaling pathways, and tumor inflammation signature. We found that ST6GAL2 expression was proportional to ICI, immunostimulator, and immune subtypes. ST6GAL2 expression first increased and then decreased during the progression of liver inflammation to HCC. The dysfunctional experiment indicated that ST6GAL2 might exert immunosuppressive effects during HCC progression through regulating ICI. Several broad-spectrum anticancer drugs were obtained by drug sensitivity prediction analysis of ST6GAL2. Conclusion: In conclusion, ST6GAL2 was a reliable prognostic biomarker strongly associated with ICI, and could be a potential immunotherapeutic target for HCC.

•Traditional Chinese medicine KXYA formula exerted an anti-HCC effect in vivo and in vitro.•Omics detection and experimental verification showed that KXYA inhibited HCC by reducing glutathione and inducing ferroptosis.•The key targets of KXYA treatment on HCC were UGDH, AKR1B10, and SLC7A11, which could be the therapeutic targets for HCC.

The JiGuCao capsule formula (JCF) has demonstrated promising curative effects in treating chronic hepatitis B (CHB) in clinical trials. Here, we aimed to investigate JCF's function and mechanism in diseases related to the hepatitis B virus (HBV). We used mass spectrometry (MS) to identify the active metabolites of JCF and established the HBV replication mouse model by hydrodynamically injecting HBV replication plasmids into the mice's tail vein. Liposomes were used to transfect the plasmids into the cells. The CCK-8 kit identified cell viability. We detected the levels of HBV s antigen (HBsAg) and HBV e antigen (HBeAg) by the quantitative determination kits. qRT-PCR and Western blot were used to detect the genes' expression. The key pathways and key genes related to JCF on CHB treatment were obtained by network pharmacological analysis. Our results showed that JCF accelerated the elimination of HBsAg in mice. JCF and its medicated serum inhibited HBV replication and proliferation of HBV-replicating hepatoma cells in vitro. And the key targets of JCF in treating CHB were CASP3, CXCL8, EGFR, HSPA8, IL6, MDM2, MMP9, NR3C1, PTGS2, and VEGFA. Furthermore, these key targets were related to pathways in cancer, hepatitis B, microRNAs in cancer, PI3K-Akt signaling, and proteoglycans in cancer pathways. Finally, Cholic Acid, Deoxycholic Acid, and 3', 4', 7-Trihydroxyflavone were the main active metabolites of JCF that we obtained. JCF employed its active metabolites to perform an anti-HBV effect and prevent the development of HBV-related diseases.

The etiology of nonalcoholic fatty liver disease (NAFLD) involves a complex interaction of genetic and environmental factors. Previous observational studies have revealed that higher leptin levels are related to a lower risk of developing NAFLD, but the causative association remains unknown. We intended to study the causal effect between leptin and NAFLD using the Mendelian randomization (MR) study. We performed a two-sample Mendelian randomization (TSMR) analysis using summary GWAS data from leptin (up to 50,321 individuals) and NAFLD (8,434 cases and 770,180 controls) in a European population. Instrumental variables (IVs) that satisfied the three core assumptions of Mendelian randomization were selected. The TSMR analysis was conducted using the inverse variance weighted (IVW) method, MR-Egger regression method, and weighted median (WM) method. To ensure the accuracy and stability of the study results, heterogeneity tests, multiple validity tests, and sensitivity analyses were conducted. The findings of the TSMR correlation analysis between NAFLD and leptin were as follows: IVW method (odds ratio (OR) 0.6729; 95