IntroductionHepatocellular carcinoma (HCC) remains a significant global public health risk, and its mortality rate remains high. Tetrandrine (TET) inhibits tumor growth, but its combination with anti-PD-1 immunotherapy has not been fully elucidated.MethodsSTING was knocked down in HCC cells, and CD8+ T cells were extracted and activated from peripheral blood. CD8+ T cells were co-cultured with HCC cells, and TET was added. This study evaluated TET’s effects on HCC malignant behavior and CD8+ T cell activation in the co-culture system. γ-H2AX and dsDNA were detected through immunofluorescence and Western blot. The interaction between TET and the proteins of STING/TBK1/IRF3 pathway was predicted by molecular docking, and the activation of this pathway was analyzed by Western blot. Subcutaneous and orthotopic HCC models were established in mice. The therapeutic effects of TET+anti-PD-1 were evaluated by tumor volume measurement, histopathological analysis and immunohistochemistry, and serum biochemical indicators were detected for safety evaluation.ResultsTET significantly inhibited HCC growth and induced apoptosis. It also promoted CD8+ T cell activation, proliferation and cytotoxicity, and enhanced their ability to secrete IFN-γ and TNF-α. TET also induced DNA damage and dsDNA accumulation, and activated STING/TBK1/IRF3 signal. STING knockdown experiments confirmed that this pathway was central for TET anti-cancer effects. In addition, TET and anti-PD-1 produced a significant synergistic anti-tumor effect, effectively inhibited HCC growth, increased CD8+ T cell infiltration, and significantly improved liver and kidney function indicators. No obvious toxic reaction was observed.DiscussionBy activating STING/TBK1/IRF3 signaling, TET enhanced CD8+ T cell-mediated anti-tumor immunity, thereby markedly enhancing anti-PD-1 therapy efficacy in HCC.

Introduction:Accurate classification of colonoscopic images is essential for early detection and characterization of colorectal diseases. Recent advances in deep learning, particularly transformer-based architectures and graph neural networks (GNNs), provide alternative strategies for modeling global contextual information and relational structures in image representations. This study evaluates transformer-based and graph-based frameworks under a unified experimental protocol for endoscopic colon disease classification. Methods:Experiments were conducted on the Kvasir V2 dataset using two primary paradigms: (i) a Vision Transformer (ViT) with selective fine-tuning and learning-rate scheduling, and (ii) a CNN-GNN pipeline integrating image embeddings with graph construction strategies (cosine similarity, k-nearest neighbors, and epsilon-radius graphs) and multiple GNN architectures. Performance was evaluated using accuracy, precision, recall, and macro-F1 score, with Grad-CAM used for qualitative interpretability analysis. Results:The selectively fine-tuned Vision Transformer achieved 94.6% accuracy with a macro-F1 score of 0.94. The best graph-based configuration (ViT embeddings with epsilon graph and GIN aggregation) achieved 92% accuracy and 0.92 macro-F1 score. Discussion:Transformer-based contextual modeling provides strong discriminative capability for image-level colon disease classification, while graph-based relational modeling offers competitive performance when paired with high-quality embeddings.

Purpose: Pancreatic cancer has the worst prognosis of all common cancers worldwide. Cadherin plays important roles in cancer cell invasion and metastasis. This study investigated the role and mechanism of Cadherin 23 (CDH23) action in the viability of pancreatic cancer cells. Methods: We examined CDH23 expression in 70 surgical pancreatic cancer samples and examined relationships among the level of CDH23 expression, clinicopathological characteristics, and the prognosis of the pancreatic cancer patients. Furthermore, we silenced CDH23 expression in pancreatic cancer cell lines (Panc-1, SUIT-2, MIA PaCa-2, CFPAC-1, and Capan-2) and assessed the viability of these cells. CDH23 expression in pancreatic cancer patients and cell lines was examined using immunohistochemistry and western blotting. Results: High levels of CDH23 in pancreatic cancer patients led to shorter overall survival and correlated with local recurrence and distance metastasis. The viability of pancreatic cancer cells in floating culture conditions decreased sharply when CDH23 was silenced. The viability and migration of pancreatic cancer cells in monolayer culture conditions did not change when CDH23 was silenced. The level of phosphorylated AKT was significantly decreased in the CDH23 knockdown cells in floating culture conditions. Conclusion: High levels of CDH23 expression are correlated with a poor prognosis in pancreatic cancer and may serve as a novel prognostic marker.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterized by high metastatic potential and a stroma-rich tumor microenvironment (TME). Dihydroartemisinin (DHA) has shown antitumor potential in various cancers, but its therapeutic effects on the TME of PDAC are not yet understood. METHODS: DHA-related differentially expressed genes (DEGs) were identified by high-throughput RNA sequencing in PDAC cells and utilized to explore the biological functions of DHA. The clinical value of DHA was examined by constructing a prognostic risk model using the TCGA dataset. We identified SERPINB5 as a downstream target of DHA involved in TME remodeling through cancer-associated fibroblast (CAF) regulation. The clinical value of SERPINB5 was validated through prognostic risk modeling and immunohistochemistry staining. RESULTS: Our findings indicate that DHA may affect CAF-mediated TME remodeling. Prognostic risk modeling indicates that DHA was associated with PDAC prognosis, implying its clinical potential. DHA may improve the prognosis of PDAC patients by downregulating the expression of SERPINB5, which may participate in regulating CAFs. CONCLUSIONS: This study suggests that DHA might improve the prognosis of PDAC patients, and it may influence the PDAC TME by downregulating SERPINB5, offering new insights into DHA’s antitumor mechanisms and its potential clinical applications in PDAC treatment.

Tumor-stromal interactions and stromal heterogeneity in the tumor microenvironment are critical factors that influence the progression, metastasis, and chemoresistance of pancreatic ductal adenocarcinoma (PDAC). Here, we used spatial transcriptome technology to profile the gene expression landscape of primary PDAC and liver metastatic PDAC after bioactive black phosphorus nanomaterial (bioactive BP) treatment using a murine model of PDAC (LSL-Kras(G12D/+); LSL-Trp53(R172H/+); and Pdx-1-Cre mice). Bioinformatic and biochemical analyses showed that bioactive BP contributes to the tumor-stromal interplay by suppressing cancer-associated fibroblast (CAF) activation. Our results showed that bioactive BP contributes to CAF heterogeneity by decreasing the amount of inflammatory CAFs and myofibroblastic CAFs, two CAF subpopulations. Our study demonstrates the influence of bioactive BP on tumor-stromal interactions and CAF heterogeneity and suggests bioactive BP as a potential PDAC treatment.

Pancreatic ductal adenocarcinoma (PDAC) is a rapidly progressing malignancy with a poor prognosis. Quercetin is a flavonoid compound with various biological benefits that can be extracted from Chinese herbs or daily foods. Quercetin has anticancer properties in various types of cancers. However, its therapeutic effects and potential mechanisms in PDAC have not been investigated extensively. Here, we confirmed the therapeutic effect of quercetin in PDAC using a mouse model. Based on high-throughput RNA sequencing (RNA-seq) and bioinformatic analysis, we propose that quercetin is involved in stromal infiltration of PDAC. Quercetin attenuates the activation of cancer-associated fibroblasts (CAFs) via tumor-stromal interaction. Meanwhile, we have identified two quercetin-related prognostic models for patients with PDAC. Finally, we proposed a downstream target of quercetin, the ITGB4 gene, which could be a potential therapeutic target for PDAC.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant and lethal human cancers in the world due to its high metastatic potential, and patients with PDAC have a poor prognosis, yet quite little is understood regarding the underlying biological mechanisms of its high metastatic capacity. Baicalein has a dramatic anti-tumor function in the treatment of different types of cancer. However, the therapeutic effects of baicalein on human PDAC and its mechanisms of action have not been extensively understood. In order to explore the biological characteristic, molecular mechanisms, and potential clinical value of baicalein in inhibiting the metastatic capacity of PDAC. We performed several in vitro, in vivo, and in silico studies. We first examined the potential regulation of baicalein in the metastatic capacity of PDAC cells. We showed that baicalein could dramatically suppress liver metastasis of PDAC cells with highly metastatic potential in mice model. The high-throughput sequencing analysis was employed to explore the biological roles of baicalein in PDAC cells. We found that baicalein might be involved in the infiltration of Cancer-Associated Fibroblasts (CAF) in PDAC. Moreover, a baicalein-related risk model and a lncRNA-related model were built by Cox analysis according to the data set of PDAC from TCGA database which suggested a clinical value of baicalein. Finally, we revealed a potential downstream target of baicalein in PDAC, we proposed that baicalein might contribute to the infiltration of CAF via FGFBP1. Thus, we uncovered a novel role for baicalein in regulation of PDAC liver metastasis that may contribute to its anti-cancer effect. We proposed that baicalein might suppress PDAC liver metastasis via regulation of FGFBP1-mediated CAF infiltration. Our results provide a new perspective on clinical utility of baicalein and open new avenues for the inhibition of liver-metastasis of PDAC.

Background and aim:HF (Heart Failure) is the leading cause of mortality and is a significant clinical problem affecting millions of patients worldwide. To date, the mechanisms of HF remain largely elusive. The effective treatments contributing to HF remain incompletely understood. Therefore, the development of an effective strategy for HF is urgently needed. Experimental procedure:In the present study, we devoted to investigating the effective treatments and sought to systematically decipher the related molecular mechanisms of Guizhigancao Decoction (GZGCD, Cinnamomum cassia Presl and Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle) for treating HF. We examined the therapeutic effect of GZGCD on HF in vivo. An integrative approach combining biomarker examination, echocardiography, myocardial fibrosis and cardiac apoptosis condition using Masson and TUNEL staining was performed to assess the efficacy of GZGCD against HF. Subsequently, comprehensive network pharmacology analyses were performed to explore the mechanisms involved in GZGCD therapeutic effects on HF. Results and conclusions:The results showed that GZGCD could reverse cardiac function in rats with HF by reducing NT-proBNP, increasing EF, decreasing LVESV, LVEDV, LVIDs, LVIDd, increasing running time, and ameliorate myocardial collagen fiber hyperplasia and cardiomyocyte apoptosis. We showed that GZGCD might contribute to HF treatment via oxidative related pathways through bioinformatics. Eventually, promising compound quercetin in GZGCD for HF therapeutics was proposed in database-based analysis. Collectively, our findings indicate that GZGCD has a treatment effect on HF. We proposed that GZGCD might contribute HF treatment via oxidative response-related pathways.

The effects of HNK, I5, and I6 on the expression of protein in hippocampus of depressed mice were studied by isobaric tags for relative and absolute quantitation (iTRAQ) to explore the mechanism of their antidepressant action. HNK, I5, and I6 were administered intragastric administration once a day in the morning for 7 days. The drug was subsequently discontinued for 7 days (without any treatment). On the 15th day, mice in each group were given the drug (1.0, 10.0, 30.0 mg/kg) intragastric stimulation and mouse hippocampal tissues were taken to perform iTRAQ to identify differentially expressed proteins, and bioinformatics was used to analyze the functional enrichment of the differentially expressed proteins. Compared with Ctr group, the number of differentially expressed proteins in HNK, I5, and I6 treatment groups was 158, 88, and 105, respectively. The three groups shared 29 differentially expressed proteins. In addition, compared with HNK group, the number of differentially expressed proteins in I5 and I6 groups was 201 and 203, respectively. A total of 47 and 56 differentially expressed proteins were co-expressed in I5 and I6 groups. Bioinformatics analysis showed that these differentially expressed proteins mainly had the functions of binding, biocatalysis, and transport, and mainly participated in cellular process, biological regulation process, biological metabolism process, and stress reaction process. GO and KEGG pathway analysis found that these differentially expressed proteins were involved long-term potentiation, G13 pathway, platelet activation pathway, and MAPK signaling pathway. HNK, I5, and I6 antidepressants are closely related to sudden stress sensitivity, stress resistance, neurotransmitter, and metabolic pathways. This study provides a scientific basis to further elucidate the mechanism and clinical application of HNK, I5, and I6 antidepressants.

目的 探讨高仿真腹腔镜模拟教学培训体系在普外科临床教学中的应用价值.方法 选取2020年10月至2021年10月于深圳大学总医院普外科实习的60名本科生作为研究对象,采用随机数字表法将其分为对照组与研究组,每组各30名.对照组实习生接受常规教学培训模式,研究组实习生接受高仿真腹腔镜模拟教学培训体系.比较两组实习生的考核成绩、教学满意度、学习兴趣、学习自主性评分.结果 研究组培训后的切割、钉转移、双手动作得分高于对照组,打结用时、连接缝合用时短于对照组,差异有统计学意义(P＜0.05).研究组的教学满意度高于对照组,差异有统计学意义(P＜0.05).两组培训前的学习兴趣、学习自主性评分比较,差异无统计学意义(P＞0.05);研究组培训后的学习兴趣、学习自主性评分高于对照组,差异有统计学意义(P＜0.05).结论 对普外科本科实习生,采取高仿真腹腔镜模拟教学培训体系可促进实习生专业技能提升,加强实习生学习积极性与主动性,改善实习生对教学方法满意度,具备一定价值.

The strong tumorigenic capacity and treatment resistance made hepatocellular carcinoma (HCC) a huge threat to public health. ZNF165, the kruppel family of zinc-finger-containing transcription factors, is expressed in HCC; however, its specific role in HCC and the molecular mechanism are yet to be elucidated. In this study, we observed that ZNF165 was overexpressed in liver cancer tissues and the immune microenvironment; higher ZNF165 expression was correlated with lower overall survival in liver cancer patients. The ZNF165 knockdown in Bel7402 cells revealed the impairment of the tryptophan/kynurenine/AhR/CYP1A1 axis. Moreover, the knockdown of CYP1A1 significantly inhibited the proliferation and migration of HCC cells, and ZNF165 promoted the transcriptional activity of AhR by facilitating the nuclear translocation of CYP1A1. In conclusion, the present study argued that ZNF165 was highly expressed in liver tissues and the immune microenvironment. ZNF165 promoted the proliferation and migration of HCC cells by activating the tryptophan/kynurenine/AhR/CYP1A1 axis and promoting the expression of CYP1A1.

Colon cancer (COAD) is a leading cause of cancer mortality in the world. Most patients with COAD die as a result of cancer cell metastasis. However, the mechanisms underlying the metastatic phenotype of COAD remain unclear. Instead, particular features of the tumor microenvironment (TME) could predict adverse outcomes including metastasis in patients with COAD, and the role of TME in governing COAD progression is undeniable. Therefore, exploring the role of TME in COAD may help us better understand the molecular mechanisms behind COAD progression which may improve clinical outcomes and quality of patients. Here, we identified a Specific TME Regulatory Network including AEBP1, BGN, POST, and FAP (STMERN) that is highly involved in clinical outcomes of patients with COAD. Comprehensive in silico analysis of our study revealed that the STMERN is highly correlated with the severity of COAD. Meanwhile, our results reveal that the STMERN might be associated with immune infiltration in COAD. Importantly, we show that dihydroartemisinin (DHA) potentially interacts with the STMERN. We suggest that DHA might contribute to immune infiltration through regulating the STMERN in COAD. Taken together, our data provide a set of biomarkers of progression and poor prognosis in COAD. These findings could have potential prognostic and therapeutic implications in the progression of COAD.

Japanese Society for Cancer of the Colon and Rectum (JSCCR) guideline 2019 recommended that lymph node dissection for advanced rectal cancer should include the lymphatic adipose tissue at the root of the inferior mesenteric vessels, but the ligation site of the inferior mesenteric artery (IMA) was not determined, and the NCCN guideline did not indicate clearly whether to retain the left colonic artery (LCA). Controversy over whether to retain LCA is no more than whether it can reduce the incidence of anastomotic complications or postoperative functional damage without affecting the patients' oncological outcome. Focusing on the above problems, this paper reviews the latest research progress. In conclusion, it is believed that the advantages of retaining LCA are supported by most studies, which can improve the blood supply of the proximal anastomosis, and technically can achieve the same range of lymph node dissection as IMA high ligation. However, whether it affects the survival of patients, reduces the incidence of anastomotic leakage, and improves the quality of life of patients, more high-quality evidence-based medical evidence is still needed.

Introduction: Pancreatic adenocarcinoma (PAAD) is an aggressive malignancy, with a major mortality resulting from the rapid progression of metastasis. Unfortunately, no effective treatment strategy has been developed for PAAD metastasis to date. Thus, unraveling the mechanisms involved in PAAD metastatic phenotype may facilitate the treatment for PAAD patients. Objectives: PIK3CB is an oncogene implicated in cancer development and progression but less is known about whether PIK3CB participates in PAAD metastasis. Therefore, the objective of this study is to explore the mechanism(s) of PIK3CB in PAAD metastasis. Methods: In our study, we examined the PIK3CB expression pattern using bioinformatic analysis and clinical material derived from patients with PAAD. Subsequently, a series of biochemical experiments were conducted to investigate the role of PIK3CB as potential mechanism(s) underlying PAAD metastasis in vivo using nude mice and in vitro using cell lines. Results: We observed that PIK3CB was involved in PAAD progression. Notably, we identified that PIK3CB was involved in PAAD metastasis. Downregulation of PIK3CB significantly reduced PAAD metastatic potential in vivo. Furthermore, a series of bioinformatic analyses showed that PIK3CB was involved in cell adhesion in PAAD. Notably, PIK3CB depletion inhibited invasion potential specifically via suppressing cell adhesion to collagen I in PAAD cells. Conclusion: Collectively, our findings indicate that PIK3CB is involved in PAAD metastasis through cell-matrix adhesion. We proposed that PIK3CB is a potential therapeutic target for PAAD therapy.

Megaduodenum is a clinical syndrome which is characterized by the remarkable expansion of duodenum. Megaduodenum can be caused by mechanical or functional chronic duodenal obstruction. Functional chronic duodenal obstruction of megaduodenum in children is a clinical syndrome characterized by non-mechanical obstruction of the duodenum and marked expansion. It is an extremely rare congenital disease. Our paper report a 1-year-old girl with functional chronic duodenal obstruction caused by megaduodenum.

Abstract Introduction Pancreatic adenocarcinoma (PAAD) is an aggressive malignancy, with a major mortality resulting from the rapid progression of metastasis. Unfortunately, no effective treatment strategy has been developed for PAAD metastasis to date. Thus, unraveling the mechanisms involved in PAAD metastatic phenotype may facilitate the treatment for PAAD patients. Objectives PIK3CB is an oncogene implicated in cancer development and progression but less is known about whether PIK3CB participates in PAAD metastasis. Therefore, the objective of this study is to explore the mechanism(s) of PIK3CB in PAAD metastasis. Methods In our study, we examined the PIK3CB expression pattern using bioinformatic analysis and clinical material derived from patients with PAAD. Subsequently, a series of biochemical experiments were conducted to investigate the role of PIK3CB as potential mechanism(s) underlying PAAD metastasis in vivo using nude mice and in vitro using cell lines. Results We observed that PIK3CB was involved in PAAD progression. Notably, we identified that PIK3CB was involved in PAAD metastasis. Downregulation of PIK3CB significantly reduced PAAD metastatic potential in vivo. Furthermore, a series of bioinformatic analyses showed that PIK3CB was involved in cell adhesion in PAAD. Notably, PIK3CB depletion inhibited invasion potential specifically via suppressing cell adhesion to collagen I in PAAD cells. Conclusion Collectively, our findings indicate that PIK3CB is involved in PAAD metastasis through cell-matrix adhesion. We proposed that PIK3CB is a potential therapeutic target for PAAD therapy.

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Rationale: Pancreatic cancer is one of the most difficult cancers to manage and its poor prognosis stems from the lack of a reliable early disease biomarker coupled with its highly metastatic potential. Liver metastasis accounts for the high mortality rate in pancreatic cancer. Therefore, a better understanding of the mechanism(s) underlying the acquisition of the metastatic potential in pancreatic cancer is highly desirable. Methods: Microarray analysis in wild-type and highly liver metastatic human pancreatic cancer cell lines was performed to identify gene expression signatures that underlie the metastatic process. We validated our findings in patient samples, nude mice, cell lines and database analysis. Results: We identified a metastasis-related gene, laminin subunit alpha 4 (LAMA4), that was upregulated in highly liver metastatic human pancreatic cancer cell lines. Downregulation of LAMA4 reduced the liver metastatic ability of pancreatic cancer cells in vivo. Furthermore, LAMA4 expression was positively correlated with tumor severity and in silico analyses revealed that LAMA4 was associated with altered tumor microenvironment. In particular, our in vitro and in vivo results showed that LAMA4 expression was highly correlated with cancer-associated fibroblasts (CAFs) level which may contribute to pancreatic cancer metastasis. We further found that LAMA4 had a positive effect on the recruitment and activity of CAFs. Conclusions: These data provide evidence for LAMA4 as a possible biomarker of disease progression and poor prognosis in pancreatic cancer. Our findings indicate that LAMA4 may contribute to pancreatic cancer metastasis via recruitment or activation of CAFs.

Dysregulated expression of the cell surface protein, CD146, has been implicated in various types of cancer in humans, including in lung cancer. The present study aimed to clarify the mechanism underlying abnormal CD146 expression in human pulmonary large cell neuroendocrine carcinoma (LCNEC) cell lines (NCI-H460 and NCI-H810). The functions of CD146 were investigated by measuring cell migration and viability following CD146 knockdown or overexpression via small interference RNA and plasmid transfection. The findings demonstrated that decreased protein expression of CD146 could inhibit migration and viability in LCNEC cells. Furthermore, CD146 was determined to influence the expression of epithelial-mesenchymal transition markers (epithelial cadherin, vimentin and Snail) and promoted AKT phosphorylation. The present results imply CD146 may function in the migration and proliferation of pulmonary LCNEC cells.

Objective To study the effect of DNA methyltransferase (DNMT1) on Marveld1 in hepatocellular Carcinoma (HCC), and explore its role in the molecular mechanism of HCC occurrence and development. Methods The expression level of Dnmt1 and Marveld1 genes was detected by RT-PCR in the intraoperative pathological specimens. The human hepatoma Bel7402 and SMMC7721 cell lines down-regulated by DNMT1 gene expression were constructed by SiRNA transfection. The methylation level of Marveld1 promoter region was detected after RT-PCR and West-blot verification. The expression of Marveld1 gene, cell proliferation, invasion and change of cell cycle were detected by RT-PCR and West-blot. The expressions of P53, CyclinD1, P21 and P16 protein were detected by West-blot method. Results The expression of DNMT1 gene in human hepatocarcinoma tissues was higher than that in adjacent tissues. The methylation level of the Marveld1 gene promoter region in human hepatoma cell line down-regulated by DNMT1 gene expression was decreased, the expression level of Marveld1 gene was increased, and the proliferation and invasion ability of cells were weakened. The cell cycle was showed as G1-S phase arrest; P53 and P16 protein expressions were up-regulated, and CyclinD1 and P21 protein expressions were down-regulated. Conclusions Dnmt1 gene is highly expressed in human hepatocarcinoma tissues. Down-regulation of DNMT1 gene expression can decrease the methylation level of Marveld1 promoter region, up-regulate Marveld1 gene and human P53 and P16 proteins expressions, and down-regulate CyclinD1 and P21 proteins expressions, inhibit the proliferation and invasion of human hepatoma cells and can cause cell cycle G1-S arrest.