Design of the distribution of iron oxide (Fe3O4) nano-particle drug in realistic cholangiocarcinoma model and the simulation of temperature increase during magnetic induction hyperthermia.

The prognosis for Cholangiocarcinoma (CCA) is unfavorable, necessitating the development of new therapeutic approach such as magnetic hyperthermia therapy (MHT) which is induced by magnetic nano-particle (MNPs) drug to bridge the treatment gap. Given the deep location of CCA within the abdominal cavity and proximity to vital organs, accurately predict the individualized treatment effects and safety brought by the distribution of MNPs in tumor will be crucial for the advancement of MHT in CCA. The Mimics software was used in this study to conduct three-dimensional reconstruction of abdominal computed tomography (CT) and magnetic reso-nance imaging images from clinical patients, resulting in the generation of a realistic digital geometric model representing the human biliary tract and its adjacent structures. Subsequently, The COMSOL Multiphysics software was utilized for modeling CCA and calculating the heat transfer law resulting from the multi-regional distribution of MNPs in CCA. The temperature within the central region of irregular CCA measured approximately 46°C, and most areas within the tumor displayed temperatures surpassing 41°C. The temperature of the inner edge of CCA is only 39 ∼ 41℃, however, it can be ameliorated by adjusting the local drug concentration through simulation system. For CCA with diverse morphologies and anatomical locations, the multi-regional distribution patterns of intratumoral MNPs and a slight overlap of drug distribution areas synergistically enhance intratumoral temperature while ensuring treatment safety. The present study highlights the practicality and imperative of incorporating personalized intratumoral MNPs distribution strategy into clinical practice for MHT, which can be achieved through the development of an integrated simulation system which incorporates medical image data and numerical calculations.

Regular use of paracetamol and risk of liver cancer: a prospective cohort study.

BACKGROUND: Paracetamol induces hepatotoxicity and subsequent liver injury, which may increase the risk of liver cancer, but epidemiological evidence remains unclear. We conducted this study to evaluate the association between paracetamol use and the risk of liver cancer. METHODS: This prospective study included 464,244 participants free of cancer diagnosis from the UK Biobank. Incident liver cancer was identified through linkage to cancer and death registries and the National Health Service Central Register using the International Classification of Diseases (ICD)-10 codes (C22). An overlap-weighted Cox proportional hazards model was utilized to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the risk of liver cancer associated with paracetamol use. The number needed to harm (NNH) was calculated at 10 years of follow-up. RESULTS: During a median of 12.6 years of follow-up, 627 cases of liver cancer were identified. Paracetamol users had a 28% higher risk of liver cancer than nonusers (HR 1.28, 95% CI 1.06-1.54). This association was robust in several sensitivity analyses and subgroup analyses, and the quantitative bias analysis indicated that the result remains sturdy to unmeasured confounding factors (E-value 1.88, lower 95% CI 1.31). The NNH was 1106.4 at the 10 years of follow-up. CONCLUSION: The regular use of paracetamol was associated with a higher risk of liver cancer. Physicians should be cautious when prescribing paracetamol, and it is recommended to assess the potential risk of liver cancer to personalize the use of paracetamol.

The Association between Long Noncoding RNA over Expression and Poor Prognosis of Liver Cancer: A Meta-Analysis.

Background: Long noncoding RNA (lncRNA) is considered to be a mediator of carcinogenesis, which may be associated with liver cancer survival. However, the relationship remains inconclusive. Meta-analysis was conducted to analytically review the association between the lncRNA expression level and clinicopathological characteristics and prognostic value of hepatic carcinoma. Materials and Methods: Four databases including Embase, PubMed, Web of Science, and the Cochrane Library were searched to collect studies about the relation between lncRNA overexpression and prognosis of liver cancer, dating from the earliest records of these databases to March 2021. Two researchers independently screened the data and literature to perform a stringent evaluation of the quality of material involved in the study. Meta-analysis was performed by Stata 16.0 software on 42 case-control studies with 6293 samples. Results: The outcomes of meta-analysis are presented as follows: lncRNA overexpression patients had later TNM stage (OR = 0.36, 95% CI (0.31, 0.41), P < 0.001), lower histological grade (OR = 0.56, 95%CI (0.49, 0.65), P < 0.001), more vascular invasion (OR = 2.02, 95% CI (1.74, 2.35), P < 0.001), bigger tumor size (OR = 2.28, 95% CI (2.00, 2.60), P < 0.001), more severe liver cirrhosis (OR = 1.39, 95% CI(0.1.16, 1.66), P < 0.001), more likely to metastasize (OR = 1.80, 95%CI(1.49, 2.18), P < 0.001), and more tumor numbers (OR = 0.72, 95% CI (0.62, 0.84), P < 0.05). lncRNA over expression patients had shorter OS (HR = 2.32, 95 CI% (2.08, 2.59), P < 0.01, RFS (HR = 2.19, 95 CI% (1.72, 2.78), P < 0.01), and DFS (HR = 2.01, 95 CI% (1.57, 2.57), P < 0.01). Conclusions: Overexposure of lncRNA is a poor prognostic feature for patients with hepatic carcinoma. The scope of our study was limited because of a lack of relevant research and the poor representativeness and varying quality of the studies involved in the current meta-analysis. Our conclusion still requires higher studies for further validation. This trial is clinically registered with CRD4201920620.