Xiaoqi Chen

Objective: To evaluate the efficacy and safety of thymosin preparations added to the same background anticancer treatment in patients with colorectal cancer. Methods: We searched nine bibliographic and trial-registration sources through 1 October 2026. Randomized controlled trials (RCTs) and nonrandomized studies with concurrent controls were eligible. Risk of bias was assessed using RoB 2 and ROBINS-I. RCTs provided the primary evidence; nonrandomized studies were analyzed separately. Review Manager 5.4.1 calculated risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals (CIs), organized by treatment setting. Sensitivity analyses, GRADE and exploratory trial sequential analysis (TSA) assessed robustness and uncertainty. Results: Thirty studies involving 2,514 participants comprised 25 RCTs (2,079 participants) and five nonrandomized studies (435 participants). In postoperative RCTs, CD4 percentage (MD 6.33, 95% CI 4.89 to 7.76), CD4/CD8 ratio (MD 0.25, 0.16 to 0.35) and NK-cell percentage (MD 6.41, 3.72 to 9.11) were higher with thymosin; CD3 and CD8 findings were inconclusive. KPS was higher in two postoperative RCTs (MD 8.50, 6.52 to 10.48) and two advanced or mixed-stage trials (MD 4.35, 1.90 to 6.80), with source-reporting concerns affecting the latter. Postoperative neutropenia was inconclusive in the RCT (RR 0.91, 0.82 to 1.01), whereas two nonrandomized studies reported a lower unadjusted risk (RR 0.65, 0.51 to 0.83). Comparable one-year survival evidence came from one trial. Certainty was low or very low. Conclusion: This review identifies RCT-based signals in circulating immune indices and performance status and clarifies the contribution of nonrandomized evidence. These findings inform the selection of outcomes and treatment settings for future trials. Current evidence is insufficient to support routine clinical use of thymosin preparations in colorectal cancer. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261467566 , CRD420261467566.

The function of Biliverdin Reductase A (BLVRA) in hepatocellular carcinoma (HCC) cells proliferation, invasion and migration remains unclear. Therefore, this research intends to explore the effect of BLVRA on HCC cells growth and metastasis. BLVRA expression was analyzed in public dataset and examined by using western blot. The malignant function of BLVRA in HCC cell lines and its effect on Wnt/β-catenin pathway were measured. Analysis from GEPIA website showed that BLVRA expression was significantly increased in HCC tissues, and high expression of BLVRA resulted in worse prognosis of HCC patients. Results from western blot showed that BLVRA expression was obviously increased in HCC cell lines. Moreover, HepG2 and Hep3B cells in si-BLVRA-1 or si-BLVRA-2 group displayed an obvious reduction in its proliferation, cell cycle, invasion and migration compared to those in the si-control group. Additionally, si-BLVRA-1 or si-BLVRA-2 transfection significantly reduced the protein levels of Vimentin, Snail1 and Snail2, as well as decreased Bcl-2 expression and increased Bax and cleaved-caspase 3 expression. Furthermore, si-BLVRA treatment inhibited the protein levels of c-MYC, β-catenin, and Cyclin D1. After IWP-4 (Wnt/β-catenin inhibitor) treatment, the proliferation ability of HCC cells was significantly reduced. BLVRA expression was significantly increased in HCC tissues and cell lines, and knocked down of BLVRA could suppress the proliferation, invasion and migration in HCC cell lines, as well as induce cell apoptosis. Moreover, si-BLVRA transfection blocked the activation of Wnt/β-catenin pathway.

Background Hepatocellular carcinoma (HCC) is one of the leading causes of death from cancer worldwide. The histopathological features, risk factors, and prognosis of HCC caused by nonalcoholic fatty liver disease (NAFLD) appear to be significantly different from those of HCC caused by other etiologies of liver disease. Objective This article explores the shared gene and molecular mechanism between NAFLD and HCC through bioinformatics technologies such as weighted gene co-expression network analysis (WGCNA), so as to provide a reference for comprehensive understanding and treatment of HCC caused by NAFLD. Methods NAFLD complementary deoxyribonucleic acid microarrays (GSE185051) from the Gene Expression Omnibus database and HCC ribonucleic acid (RNA)-sequencing data (RNA-seq data) from The Cancer Genome Atlas database were used to analyze the differentially expressed genes (DEGs) between NAFLD and HCC. Then, the clinical traits and DEGs in the two disease data sets were analyzed by WGCNA to obtain W-DEGs, and cross-W-DEGs were obtained by their intersection. We performed subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) enrichment analyses of the cross-W-DEGs and established protein–protein interaction networks. Then, we identified the hub genes in them by Cytoscape and screened out the final candidate genes. Finally, we validated candidate genes by gene expression, survival, and immunohistochemical analyses. Results The GO analysis of 79 cross-W-DEGs showed they were related mainly to RNA polymerase II (RNAP II) and its upstream transcription factors. KEGG analysis revealed that they were enriched predominantly in inflammation-related pathways (tumor necrosis factor and interleukin-17). Four candidate genes (JUNB, DUSP1, NR4A1, and FOSB) were finally screened out from the cross-W-DEGs. Conclusion JUNB, DUSP1, NR4A1, and FOSB inhibit NAFLD and HCC development and progression. Thus, they can serve as potential useful biomarkers for predicting and treating NAFLD progression to HCC. None. None. All the basic data involved in the analysis of this paper have been uploaded as Supplementary Files (SF), including the GSE185051 data set and the TCGA database gene expression matrix (SF 1, 2), and their differential gene matrix (SF 3, 4). The clinical phenotype information of the samples corresponding to the gene matrix (SF 5, 6) and the cross-W-DEGs of NAFLD and HCC (SF 7) were also included. KEGG, GO, PPI, and CytoHubba analysis results of cross-W-DEGs (SF 8, 9, 10, 11), the expression level validation results (SF 12, 13, 14), and the survival analysis results (SF 15, 16, 17, 18) of the candidate genes were also uploaded in the Supplementary Files. Z.X. realized the conception, data collection, and analysis in the article. H.J. performed the writing and editing. The remaining authors provided editing and writing assistance. All authors contributed to this article and read the submitted final version. ^# These authors contributed equally to this work. Article published online: 10 July 2023 © 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/) Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Background and aim: Hepatocellular carcinoma (HCC) is one of the ten most common malignant tumors in the world, and it is a major problem in the world. Traditional Chinese medicine (TCM) has many advantages in the prevention and treatment of HCC, but its complicated mechanism of action is difficult to clarify, which limits its research and development. The continuous development of bioinformation technology provides new methods and opportunities for the research of traditional Chinese medicine. This study uses modern network pharmacology and bioinformatic methods to explore the possible molecular mechanism of the Chinese herbal compound Fuzheng Xiaoliu Granule (FZXLG) to treat HCC, to provide a theoretical basis for their clinical application and basic research, to promote the modernization of traditional Chinese medicine and to promote its worldwide application. Methods: The active ingredients of FZXLG were collected and screened through TCMSP, BATMAN-TCM, and other databases. The targets of FZXLG were predicted by PubChem and SwissTargetPrediction; HCC disease-related targets were obtained by GeneCards, OMIM, and other disease databases, and the potential gene targets of FZXLG for HCC treatment were screened. The "Prescription-TCMs-Ingredients-Targets" network for FZXLG for the treatment of HCC was constructed, along with the screening of core effective components. The differentially expressed genes(DEGs) of HCC tumor and non-tumor adjacent tissues combined with clinical data in the TCGA database were analyzed to obtain the prognostic genes of HCC. Then, FZXLG genes affecting HCC prognosis were screened, and further screening the core target genes. The correlation between core gene expression with prognosis, immune cell infiltration, and immunohistochemical changes in HCC patients was studied. KEGG enrichment analysis and GO enrichment analysis of the FZXLG genes affecting HCC prognosis were performed by using DAVID database. AutoDockTools software was then used for molecular docking verification. Results: The ten core effective ingredients of FZXLG for HCC treatment included multiple flavonoids ingredients such as quercetin, luteolin, and formononetin. 11 core targets of FZXLG affecting the prognosis of HCC were screened, among which ESR1 and CAT were favorable prognostic factors, while EGF, MMP9, CCNA2, CCNB1, CDK1, CHEK1, and E2F1 were adverse prognostic factors. MMP9 and EGF were positively correlated with six TIIC subsets. The different expression levels of CAT, PLG, AR, MMP9, CCNA2, CCNB1, CDK1, and E2F1 were correlated with the immunohistochemical staining changes in normal liver and liver cancer. KEGG pathway enrichment analysis yielded 33 pathways including cell cycle, p53, hepatitis B, and other signaling pathways. Molecular docking verified that the main core components had good binding to the protective prognostic core targets ESR1 and CAT. Conclusions: FZXLG may treat HCC through multiple ingredients, multiple targets, and multiple pathways, affecting the prognosis, immune microenvironment, and immunohistochemical changes of HCC. Relevance for patients: FZXLG is a Chinese herbal compound for the treatment of hepatocellular carcinoma, with significant clinical efficacy. However, the mechanism of action is unclear and lacks theoretical support, which limits its popularization application. This study preliminarily revealed its molecular mechanism, providing a theoretical basis for its clinical application, which can better guide its clinical popularization application, and also provide a new strategy for the treatment of HCC.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer associated with a poor prognosis. ICC accounts for about 10% of primary liver malignancies but with increasing incidence in recent years. Recently, some studies suggested that minimally interventional therapy can be used in the treatment of ICC. However, there are few references on interventional therapy for the clinical treatment of ICC. Herein we reported a case of a 48-year-old man who suffered from ICC. The patient was diagnosed with ICC by computerized tomography scan and pathological biopsy. The patient was completely cured by minimally interventional therapy with iodine-125 seed implantation. These results provide an important reference for the treatment option of ICC.

Hypoxia‑inducible‑factor 1α (HIF‑1α) is a marker for poor prognosis in the majority of the cancer types, and it has been revealed to be essential for maintaining cancer stem cells (CSCs). In the present study, it was determined that the expression of HIF‑1α and CSC‑related genes under hypoxic conditions was upregulated. Stable knockdown of HIF‑1α significantly inhibited cell proliferation, migration and tumour growth in vivo in oesophageal squamous cell carcinoma (ESCC). A previous study revealed that the Wnt/β‑catenin pathway may play a key role in maintenance and progression of CSCs. Therefore, it was also revealed that stable knockdown of HIF‑1α reduced the formation of spheroid body cells, the expression of CSC‑related genes and Wnt/β‑catenin pathway‑related target genes, as well as the activity of the Wnt/β‑catenin pathway. Collectively, the present results indicated that HIF‑1α may regulate the stemness of ESCC by activating the Wnt/β‑catenin pathway.