Prostate cancer (PCa) ranks as the second most prevalent malignancy among men worldwide. Early diagnosis, personalized treatment, and prognosis prediction of PCa play a crucial role in improving patients' survival rates. The advancement of artificial intelligence (AI), particularly the utilization of deep learning (DL) algorithms, has brought about substantial progress in assisting the diagnosis, treatment, and prognosis prediction of PCa. The introduction of the foundation model has revolutionized the application of AI in medical treatment and facilitated its integration into clinical practice. This review emphasizes the clinical application of AI in PCa by discussing recent advancements from both pathological and imaging perspectives. Furthermore, it explores the current challenges faced by AI in clinical applications while also considering future developments, aiming to provide a valuable point of reference for the integration of AI and clinical applications.
Humans ; Prostatic Neoplasms/diagnosis* ; Male ; Artificial Intelligence ; Deep Learning ; Prognosis

OBJECTIVES: To analyze the differentially expressed exosomal miRNAs in patients with chronic heart failure (CHF) complicated by hyperuricemia (HUA) and explore their potential as novel diagnostic molecular markers and their target genes. METHODS: This study was conducted among 30 CHF patients with HUA (observation group) and 30 healthy volunteers (control group) enrolled between September, 2020 and September, 2023. Peripheral blood samples were collected from 6 CHF patients with HUA for analyzing exosomal miRNAs by high-throughput sequencing, and the results were validated in the remaining 24 patients using qRT-PCR. GO and KEGG enrichment analyses were performed to predict the the target genes of the identified differential miRNAs. We also validated the differentially expressed miRNAs by animal experiment. RESULTS: A total of 42 differentially expressed exosomal miRNAs were detected in observation group by high-throughput sequencing; among them, miR-27a-5p was significantly upregulated (P=0.000179), and miR-139-3p was significantly downregulated (P=0.000058). In the 24 patients with both CHF and PUA, qRT-PCR validated significant upregulation of miR-27a-5p (P=0.004) and downregulation of miR-139-3p (P=0.005) in serum exosomes. When combined, miR-27a-5p and miR-139-3p had a maximum area under the curve (AUC) of 0.899 (95% CI: 0812-0.987) for predicting CHF complicated by HUA. GO and KEGG enrichment analyses suggested that the differential expressions of miR-27a-5p and miR-139-3p was associated with the activation of the AMPK-mTOR signaling pathway to activate the autophagic response. We obtained the same conclusion from animal experiment. CONCLUSIONS Upregulated exosomal miR-27a-5p combined with downregulated exosomal miR-139-3p expression can serve as a novel molecular marker for diagnosis of CHF complicated by HUA, and their differential expression may promote autophagy in cardiomyocytes by activating the AMPK-mTOR signaling pathway.
Humans ; Hyperuricemia/diagnosis* ; Heart Failure/genetics* ; MicroRNAs/metabolism* ; Exosomes/metabolism* ; Chronic Disease ; Male ; Female ; Middle Aged ; Animals

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Pain is a prevalent symptom in both cancer and non-cancer end-stage diseases, often being the most feared by patients and significantly impacting their quality of life.Hospice care aims to address physical, psychological, spiritual, and other needs of patients and their families during this stage, with a focus on alleviating pain and discomfort.Effective pain management is a crucial component of hospice care, particularly given the increasing prevalence of cancer and chronic diseases in China and the growing elderly population.To provide analgesic management for hospice patients, a thorough assessment of pain is essential to identify its type and characteristics.Treatment approaches may include etiological interventions, pharmacotherapy, interventional therapy, physiotherapy, psychotherapy, and comfort care, all aimed at achieving comprehensive pain management.The use of opioid should be carefully guided by scientific principles to minimize adverse effects and optimize pain relief, ultimately enhancing patients' end-of-life quality of life.

Traditional in vitro models have inevitable limitations and there are significant differences in assessing drug efficacy and side effects as compared to human trials.Organ-on-a-chip technology simulates human organs in a physiological environment and functional chip with a high fidelity physiological or pathophysiological level,offering great innovative prospects for drug development.This paper mainly introduces the research progress and application of organ chip from the perspective of various systems in vivo.At the same time,the limitations of the current devel-opment process of organ chip and the future development direction are proposed.

More and more in-depth tumor mechanism research and clinical precision treatment have put forward higher requirements for the technology for the establishment of tumor models.More and more tumor organoids have been applied.This model is able to reproduce the genomic,transcriptome,proteome and other omics features of pa-rental tumors without heterogeneity found in cell line models.Based on these characteristics,tumor organoids have gradually become a representative preclinical model,facilitating the translation of new research results and precision treatment of patients.This article summarizes the latest progress of tumor organoids on R&D of technology and appli-cation,focusing on the current methods of establishing tumor organoids,opportunities and challenges in clinical and research application.

Objective To establish breast cancer organoids for a long time and to characterize their molecular ex-pression and test their sensitivity to chemotherapy drugs.Methods Breast cancer specimens were digested with col-lagenase to release cancer cells for organoid culture.The organoids were characterized by morphology and ER,PR,HER-2,CK expression by technology of histoimmunofluorescence.Among them,three were tested for paclitaxel,doxorubicin and cisplatin sensitivity.Results A total of 44 cases of breast cancer organoids were established,all of which showed dense spherical-like growth and ER,PR,HER-2,CK,matching their clinical counterpart.Breast cancer organoids were sensitive to chemotherapy drugs paclitaxel,doxorubicin and cisplatin.Conclusions Organoid model,as a new in vitro may reproduce the pathophysiology features with heterogeneity.

Objective To establish human and mouse pancreatic cancer cell strains stably expressing Cas9 protein,green fluorescent protein,red fluorescent proteins,luciferase-tdTomato,and to validate the activity of luciferase and gene editing of Cas9 function for pancreatic cancer research using luciferase and CRISPR/Cas9 system.Methods In human pancreatic cancer cells(AsPC-1,CFPAC-1,HPAC,BxPC-3,HS 766T,MIA PaCa-2,PANC-1,and SW 1990),and mouse pancreatic cancer cell(Pan02),the cells were infected with Cas9-expressing plas-mid pLv-EF1α-Cas9m1.1-Puro,and single-cell clones were selected for culture and expansion.After extracting the total protein,Western blot verified the expression level of Cas9;Infected with fluorescent protein expression plasmids pLv-EF1α-EGFP,pLv-EF1α-mCherry,pLv-EF1α-tdTomato,pLv-EF1α-Luc2-tdT,and selected single cell clones stably expressing fluorescent proteins were cultured and amplified under fluorescence microscope.Cas9 stable expression cell line was selected to be infected with pLv-EF1α-Luc2-tdT,and the mono-clonal culture of stable expression of fluorescent proteins was selected for expansion under fluorescence micro-scope.One of the cell lines were selected to be infected with Lv-EF1a-mCherry,and the mCherry-positive cells were sorted out by flow cytometry,and then the guide RNA of mCherry gene was then infected by lentivirus to tar-get the mCherry gene,and after cell expansion,mCherry knockdown was detected by fluorescence microscope observation and flow cytometry;5 BALB/c Nude mice were subcutaneously inoculated with MIA PaCa-2-Luc2-tdT cells(1.0×107/cells each),and imaged in vivo after 36 days.Results 48 human pancreatic cancer cell strains with stable Cas9 expression were screened(including 23 cells expressing Cas9m1.1,25 cells expressing Cas9m1.1-Luc2-tdT),33 pancreatic cancer cell strains with stable expression of fluorescent proteins were screened(8 cells expressing EGFP,7 expressing mCherry,and 9 each expressing Luc2-tdT and tdTomato).Cells expressing mCherry and Cas9 were infected with mCherry gRNA and mCherry was knocked down.In vivo imaging showed that both bioluminescence and fluorescence luminescence were present in MIA PaCa-2 cells ex-pressing Luc2-tdT.Conclusions 33 pancreatic cancer cell strains with stable expression of fluorescent proteins are successfully established,in which the Luc2-tdT-expressing cell strains have luciferase activity;48 pancreatic cancer cell strains with stable expression of Cas9 are successfully established,and the Cas9 protein has gene edi-ting activity,gene editing activity varies depending on the original cell strains.

Objective:To study the effect of baicalein on the expression of glutamate receptor related protein in PC12 cells injured by Aβ 25-35. Methods:PC12 cells were divided into control group, model group, estradiol group and baicalein group with different concentrations. The survival condition of PC12 cells in each group were detected by thiazole blue (MTT). PC12 cells were divided into control group, model group, estradiol group and baicalein group. The control group and model group were cultured with DMEM medium, and the estradiol group was added with 1×10 -3 μmol/L estradiol DMEM medium, baicalein group was added with 1 μmol/L baicalein DMEM medium. After 2 hours of intervention, 20 μmol/L Aβ 25-35 was added to the model group, estradiol group and baicalein group with induced PC12 cell injury. After 22 hours of intervention, flow cytometry was used to detect the apoptosis of PC12 cells. The expression of estrogen receptor β (ER β), phosphorylated c-Jun N-terminal kinase (p-JNK/JNK) and ionic receptor N-methyl-D-aspartate receptor 1 (NMDAR1), glutamate receptor 2 (GluR2) and calcium/calmodulin dependent protein kinase Ⅱ (CaMK Ⅱ) were detected by Western blot. Results:Compared with model group, 1 μmol/L baicalein significantly increased the proliferation rate [(95.80±2.47)% vs. (64.34±3.84)%]. The apoptosis rate of PC12 cells[(7.83±0.67)% vs. (12.84±0.91)%] was significantly decreased in baicalein group ( P<0.01). The expression of NMDAR1 (0.582±0.012 vs. 0.352±0.012), GluR2(0.538±0.017 vs. 0.355±0.006), ER β (0.362±0.015 vs. 0.262±0.018) in baicalein group were significantly increased ( P<0.01), the expression of p-JNK/JNK (0.476±0.013 vs. 0.752±0.014) and CaMK Ⅱ(0.499±0.019 vs. 0.670±0.016) in baicalein group were significantly decreased ( P<0.01). Conclusions:Baicalein has a protective effect on PC12 cells injured by Aβ 25-35. Its mechanism may be related to the inhibition of p-JNK/JNK activity by activating ERβ and regulating the expression of glutamate receptor related protein.

Hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC) is one of the most frequently occurring cancers. Hepadnaviral DNA integrations are considered to be essential agents which can promote the process of the hepatocarcinogenesis. More and more researches were designed to find the relationship of the two. In this study, we investigated whether HBV DNA integration occurred at sites of DNA double-strand breaks (DSBs), one of the most detrimental DNA damage. An 18-bp I-SceI homing endonuclease recognition site was introduced into the DNA of HepG2 cell line by stable DNA transfection, then cells were incubated in patients' serum with high HBV DNA copies and at the same time, DSBs were induced by transient expression of I-SceI after transfection of an I-SceI expression vector. By using nest PCR, the viral DNA was detected at the sites of the break. It appeared that integration occurred between part of HBV x gene and the I-Scel induced breaks. The results suggested that DSBs, as the DNA damages, may serve as potential targets for bepadnaviral DNA insertion and the integrants would lead to widespread host genome changes necessarily. It provided a new site to investigate the integration.