[This corrects the article DOI: 10.3389/fpubh.2025.1631442.].

BACKGROUND Bilateral multilobular hepatocellular carcinoma (HCC) complicated by HCC-derived biliary tumor thrombus is classified as an advanced-stage disease. Owing to the heavy tumor burden, obstructive jaundice, and other issues, the prognosis with conventional treatment is extremely poor, and most patients lose the opportunity for radical resection. The advent of immune-combined targeted conversion therapy has brought new hope for such patients. CASE SUMMARY A 36-year-old man with >= 10-year history of hepatitis B was admitted for upper abdominal distension and pain. Imaging demonstrated bilateral multifocal HCC with a left HCC-derived biliary tumor thrombus (Chinese Liver Cancer stage IIIa, Barcelona Clinic Liver Cancer stage C), obstructive jaundice, and cirrhosis. The tumor was initially considered unresectable. The patient received conversion therapy with camrelizumab, apatinib mesylate, and radiofrequency ablation. After five cycles, both the tumors and thrombus regressed, and tumor marker levels decreased markedly. The response was assessed as partial response according to mRECIST 1.1 criteria. Liver function improved from Child-Pugh class B to class A, allowing radical surgical resection with negative margins. Postoperative maintenance therapy was administered for 1 year. No recurrence was detected during follow-up. CONCLUSION For advanced bilateral multi-lobular HCC complicated by HCC-derived biliary tumor thrombus, immune-targeted therapy combined with local ablation reduces tumor burden, eliminates thrombus, converts unresectable disease to resectable status, and achieves effective short-term disease control.

Esophageal squamous cell carcinoma (ESCA) remains a lethal disease with few reliable biomarkers for early diagnosis or treatment selection. In this study, we combined bulk RNA-seq (TCGA-ESCA, GSE53625) and single-cell RNA-seq (GSE196756) data to derive and characterize an exosome-related gene signature. Using LASSO-Cox regression on 121 literature-curated exosomal genes, we established a nine-gene risk model that stratified ESCA patients into high- and low-risk groups with significantly different overall survival. This signature was validated computationally in two independent bulk cohorts and shown to correlate with established clinical parameters. Functional assays for one model component, HAPLN3, confirmed its tumor-suppressive role: HAPLN3 overexpression inhibited ESCA cell proliferation and promoted apoptosis. To explore immunotherapy relevance, we analyzed anti-PD-L1 response in the IMvigor210 bladder cancer cohort-chosen because of shared squamous histology and PD-L1 pathways-to show that low-risk patients exhibited higher response rates and longer survival. Finally, single-cell analysis mapped each signature gene to specific tumor microenvironment compartments, and integrative genomic profiling linked risk scores to copy number variation and DNA methylation changes. Together, our findings define a functionally informed exosomal biomarker panel for ESCA prognosis and suggest its potential to guide immunotherapy, with further validation in ESCA-specific immunotherapy cohorts underway.

Background: Breast phyllodes tumor (PT) is a biphasic tumor and constitutes about 0.3% to 1% of all breast tumors. The PT is histologically classified as benign, borderline, and malignant subtypes. Unlike epithelial breast cancers, PT is derived from breast fibroepithelial tissues, and the genomic information of PT subtypes is still limited. Objectives: The objectives were to gain a deeper understanding of genomic changes in the progression of PTs from benign and borderline to malignant. Design: In this study, we used an Affymetrix OncoScan Array to analyze the genome-wide copy number variations (CNVs) and nucleotide point mutations from 3 benign PTs, 3 borderline PTs, and 3 malignant PTs collected from the First Affiliated Hospital of Zhengzhou University. Methods: DNA was extracted from formalin-fixed paraffin-embedded (FFPE) specimens using the TIANamp FFPE DNA Kit. The DNA was profiled for genome-wide CNV using the Affymetrix OncoScan Array and analyzed using the Nexus Express Chromosome Analysis Suite. Results: Our in silico variation analysis indicated copy number loss in Xp11.22 to q22.1 of all benign PTs (χ 2 = 9, P = .0027) and 22q11.23 and Xq23 in all malignant PTs (χ 2 = 12, P = .0005). A copy number gain was observed in 1p13.3 of all borderline PTs (χ 2 = 9, P = .0027) and 7p11.2 of all malignant PTs (χ 2 = 9, P = .0027). We also found consistent loss of heterozygosity (LOH) in 32 loci of benign PTs, 32 loci of borderline PTs, and 23 loci of malignant PTs. Among the 87 LOH, there were 15 overlapping loci across all PT subtypes. We observed missense mutations of NRAS , KRAS , IDH2 , TP53 , and a frameshift deletion in PTEN of sequenced PT samples, irrespective of their subtype. Interestingly, a point mutation in EGFR/EGFR-AS1 was only observed in malignant PTs. Conclusions: Our data suggested that CNV at 7p11.2, 22q11.23, and Xq23 together with a point mutation in EGFR / EGFR-AS1 uniquely presented in malignant PTs may correlate with the progression of PTs.

Gastrointestinal polyps are observed and treated under endoscopy, so there presents significant challenges to advance endoscopy imaging segmentation of polyps. Current methodologies often falter in distinguishing complex polyp structures within diverse (mucosal) tissue environments. In this paper, we propose the Frequency Attention-Embedded Network (FAENet), a novel approach leveraging frequency-based attention mechanisms to enhance polyp segmentation accuracy significantly. FAENet ingeniously segregates and processes image data into high and low-frequency components, enabling precise delineation of polyp boundaries and internal structures by integrating intra-component and cross-component attention mechanisms. This method not only preserves essential edge details but also refines the learned representation attentively, ensuring robust segmentation across varied imaging conditions. Comprehensive evaluations on two public datasets, Kvasir-SEG and CVC-ClinicDB, demonstrate FAENet’s superiority over several state-of-the-art models in terms of Dice coefficient, Intersection over Union (IoU), sensitivity, and specificity. The results affirm that FAENet’s advanced attention mechanisms significantly improve the segmentation quality, outperforming traditional and contemporary techniques. FAENet’s success indicates its potential to revolutionize polyp segmentation in clinical practices, fostering diagnosis and efficient treatment of gastrointestinal polyps.

The invasion of bacteria and inflammation impeded infected wounds heal. Here, a hyaluronan-based scaffold (HAG-g-C) was designed by cross-linking with gallic acid-modified gelatin to provide a protein microenvironment and decorated with cathelicidin-BF (CBF), a natural antimicrobial peptide, to remove bacterial infections and reverse the inflammatory environment. In vitro, HAG-g-C presented an antibacterial effect on Staphylococcus aureus and Escherichia coli. Meanwhile, it could drive the phenotypic switch of macrophage from M1 to M2 to accelerate tissue remodeling. In a mouse model of S. aureus-infected total skin defects, HAG-g-C inhibited the process of infection at the beginning of the wound and then regulated the M1 macrophage transformed to M2 phenotype on day 12. In addition, HAG-g-C induced collagen deposition, and reduced the expression of TNF-α, thereby significantly accelerating the reconstruction of infected wounds.

Abstract Purpose Previous studies have shown that fibrinogen and albumin are closely related to sepsis. However, the role of fibrinogen (FIB) to albumin (ALB) ratio (FAR) in sepsis was still unclear, especially in neonates. Thus, this study is aimed at investigating whether FAR could independently predict the presence and severity of sepsis in neonates. Methods In this paper, clinical and laboratory data of 1292 neonates were retrospectively collected and divided them into three groups according to clinical diagnosis: control group (n = 555), mild sepsis group (n = 312), and severe sepsis group (n = 425). Neonates with sepsis were further divided into mild sepsis and severe sepsis group according to the severity of sepsis. All statistical analyses were performed using the statistical package SPSS 26.0, as appropriate. Results FAR levels were higher in neonates with sepsis. The prevalence of neonates with overall sepsis, mild sepsis and severe sepsis increased significantly from FAR tertile 1 to tertile 3. Multiple logistic regression analysis showed that FAR was an independent risk factor for the presence of sepsis (OR = 8.641, 95% CI 5.708–13.080, P < 0.001) and severe sepsis (OR = 2.817, 95% CI 1.701–4.666, P < 0.001). ROC curve analysis showed that FAR had a well discriminatory power in predicting sepsis (AUC = 0.67,95% CI 0.64–0.70, P < 0.001) and severe sepsis (AUC = 0.60, 95% CI, 0.57–0.64, P = 0.018). Conclusion In the current study, we demonstrated that FAR was an independent predictor for the presence and severity of neonatal sepsis.

患者 男性，49岁，主因“右上腹间断隐痛2个月余”于2020年2月28日收入我院。2个月前患者无明显诱因出现右上腹间断隐痛，无放射痛。自行口服“消炎利胆片”，其间症状加重，至当地医院行上腹增强CT检查，结果提示肝实性占位，考虑肝癌；实验室检查诊断乙肝，予口服恩替卡韦片（0.5 mg/d）抗病毒治疗。为进一步治疗就诊于我院。既往史无特殊。母亲曾患肝硬化，因“肝病”去世。入院后体检未见明显阳性体征。实验室检查：甲胎蛋白>1 210.00 μg/L，癌胚抗原及CA19-9均在正常范围，乙肝表面抗原、表面e抗体、核心抗体阳性，乙肝病毒DNA定量检测549 IU/ml。肝功能Child-Pugh分级为A级。入院行腹部增强MRI检查结果提示肝右叶占位，大小约10.3 cm×10.7 cm×14.3 cm，动脉期不均匀强化，静脉期及延迟期强化减退，腔静脉、肝右静脉、肝门静脉右支及主干多发栓子形成；肝硬化、脾大（图1）。根据《原发性肝癌诊疗指南（2019年版）》，初步诊断为：（1）原发性肝癌，中国肝癌分期Ⅲa期；巴塞罗那肝癌临床分期为C期；（2）慢性乙肝；（3）肝硬化；（4）脾大、脾功能亢进。

Background: The alterations in metabolic profile of tumors have been identified as one of the prognostic hallmarks of cancers, including osteosarcoma. These alterations are majorly controlled by groups of metabolically active genes. However, the regulation of metabolic gene signatures in tumor microenvironment of osteosarcoma has not been well explained. Objectives: Thus, we investigated the sets of previously published metabolic genes in osteosarcoma patients and normal samples. Methods: We applied computational techniques to identify metabolic genes involved in the immune function of tumor microenvironment (TME) and survival and prognosis of the osteosarcoma patients. Potential candidate gene PAICS (phosphoribosyl aminoimidazole carboxylase, phosphoribosyl aminoimidazole succino carboxamide synthetase) was chosen for further studies in osteosarcoma cell lines for its role in cell proliferation, migration and apoptosis. Results: Our analyses identified a list of metabolic genes differentially expressed in osteosarcoma tissues. Next, we scrutinized the list of genes correlated with survival and immune cells, followed by clustering osteosarcoma patients into three categories: C1, C2, and C3. These analyses led us to choose PAICS as potential candidate gene as its expression showed association with poor survival and negative correlation with the immune cells. Furthermore, we established that loss of PAICS induced apoptosis and inhibited proliferation, migration, and wound healing in HOS and MG-63 cell lines. Finally, the results were supported by constructing and validating a prediction model for prognosis of the osteosarcoma patients. Conclusion: Here, we conclude that metabolic genes specifically PAICS play an integral role in the immune cell infiltration in osteosarcoma TME, as well as cancer development and metastasis.

Anemia is one of the most common manifestations in patients with cancer. Recently, multiple studies have shown a positive correlation between pretreatment anemia and tumor prognosis. Yet, the relationship between pretreatment anemia and the prognosis of soft tissue sarcomas (STS) is unclear.We searched the PubMed and EMBASE databases to identify relevant studies. Eligible studies were included according to the inclusion criteria to assess the relationship between pretreatment anemia and the prognosis of patients with STS. Prognostic significance was determined by studying hazard ratios (HR) and 95% confidence intervals (CIs).A total of 12 studies are included. If there is significant heterogeneity, a random-effects model is used. Pooled data indicated that pretreatment anemia is related to poor overall survival (HR = 2.13; 95%CI = 1.52-2.98), disease-specific survival (HR = 1.53; 95%CI = 1.20-1.96), and disease-free survival (HR = 1.55; 95%CI = 1.10-2.17). The results of the subgroup analysis also support this conclusion.Our results suggest that pretreatment anemia may be a prognostic biomarker for STS.

Background: Anemia is one of the most common manifestations in patients with cancer. Recently, multiple studies have shown a positive correlation between pretreatment anemia and tumor prognosis. Yet, the relationship between pretreatment anemia and the prognosis of soft tissue sarcomas (STS) is unclear. Methods: We searched the PubMed and EMBASE databases to identify relevant studies. Eligible studies were included according to the inclusion criteria to assess the relationship between pretreatment anemia and the prognosis of patients with STS. Prognostic significance was determined by studying hazard ratios (HR) and 95% confidence intervals (CIs). Results: A total of 12 studies are included. If there is significant heterogeneity, a random-effects model is used. Pooled data indicated that pretreatment anemia is related to poor overall survival (HR = 2.13; 95%CI = 1.52-2.98), disease-specific survival (HR = 1.53; 95%CI = 1.20-1.96), and disease-free survival (HR = 1.55; 95%CI = 1.10-2.17). The results of the subgroup analysis also support this conclusion. Conclusion: Our results suggest that pretreatment anemia may be a prognostic biomarker for STS.

骨尤文肉瘤是一种多见于儿童及青少年的原发性骨肿瘤.骨外尤文肉瘤/外周原始神经外胚层肿瘤较为少见,多位于深部软组织,其中位于十二指肠更为罕见,治疗方式多以手术为主,现报道1例患者的治疗经过,供临床参考.

BACKGROUND:Glioma is the central nervous system tumor with the highest incidence rate and the molecular detection of gliomas has been the focus of research. This study aimed to investigate the guiding effect of cluster of differentiation 276 (CD276) expression on the clinical prognosis of glioma.METHODS:The TCGA and CGGA databases were used to study whether CD 276 can be used as an independent prognostic factor for gliomas. Immunohistochemistry was used to detect the expression of CD276, isocitrate dehydrogenase-1 (IDH1), matrix metallopeptidase 9 (MMP9), p53, and Ki-67, and 1p/19q co-deletion was detected by fluorescence in situ hybridization (FISH). The effects of CD276 RNA interference (RNAi) on cell invasion, cell cycle and the expression of β-catenin, tumor necrosis factor receptor 1 (TNFR1), and MMP9 were observed. Furthermore, the biological effects of CD276 gene knockout on intracranial transplanted tumors in nude mice were studied.RESULTS:CD276 expression was positively correlated with the extracellular matrix, collagen decomposition, and cell adhesion molecules. Immunohistochemistry and FISH showed that CD276 expression positively correlated with the glioma grade, p53 mutation, Ki-67 proliferation, and MMP9 expression; however, it negatively correlated with IDH1 mutation, 1p/19q co-deletion, and the survival rate. CD276 RNAi in U87 cells inhibited cell proliferation, migration, and invasion, but had no effect on the cell cycle. CD276 inhibited the expression of β-catenin, TNFR1, and MMP9 in U87 cells at the mRNA and protein levels. In vivo experiments showed that the tumor formation and invasion of the CD276 small interfering RNA glioma cell line in nude mice were reduced and the survival time was prolonged.CONCLUSIONS:The present study demonstrated that high expression of CD276 in gliomas indicates a poor prognosis.

病人,女,29岁,已婚.因上腹疼痛不适15天,发现肝占位7天于2019年2月12日入院.15天前无明显诱因出现上腹疼痛不适,伴有纳差、乏力,行彩超检查提示:肝内多发稍高回声团.随后行上腹部平扫MRI检查提示:肝内多发占位,考虑不典型肝细胞肝癌可能性大;肝右叶胆管细胞癌并肝内转移,转移瘤暂不除外.既往体健,无吸烟、饮酒史,否认结核、疟疾等传染病病史,无既往手术史,无输血、献血史,乙肝、丙肝等病毒性肝炎病史不详.

Propranolol has a significant anti-cancer effect towards various cancers. Our study aimed at investigating the underlying mechanism of Propranolol's therapeutic effect towards ovarian cancer. Specifically, Propranolol significantly reduced the viability of human ovarian cancer cell lines SKOV-3 and A2780 in a dose- and time-dependent manner. Flow cytometry analysis revealed that Propranolol induced the cell cycle arrest at G2/M phase therefore leading to apoptosis. Moreover, autophagy inhibitor 3-MA markedly enhanced the Propranolol-induced apoptosis. In addition, reactive oxygen species (ROS) increased dramatically after Propranolol treatment and Propranolol activated the phosphorylation of JNK. What is more, p38 inhibitor SB203580 and JNK inhibitor SP600125 attenuated the upregulated expression of LC3-II and cleaved-caspase-3 by the effect of Propranolol. ROS exclusive inhibitor antioxidant N-acetyl cysteine (NAC) weakens the phosphorylation of JNK proteins induced by Propranolol. In summary, these results suggested that Propranolol induced cell apoptosis and protective autophagy through the ROS/JNK signaling pathway in human ovarian cancer cells.

Background: Glioblastoma (GBM) is one of the most deadly primary malignant brain tumors in adults. R132H mutation of isocitrate dehydrogenase 1 (IDH1) predicts a better prognosis of GBM. IDH1-R132H is associated with increased hypoxia-inducible factor-1α (HIF-1α) expression in GBM tumors. However, the molecular mechanism underlying IDH1-R132H-HIF-1α signaling in GBM is still unclear. Aim: We aimed to investigate the molecular pathway of IDH1-R132H-HIF-1α in the regulation of GBM. Materials and Methods: U87 and U251 GBM cells and xenograft tumor mice were used. Results: We found that overexpression of IDH1-R132H decreased cell proliferation, increased apoptosis, decreased migration and invasion, enhanced temozolomide (TMZ)-induced cytotoxicity, and reduced tumor growth in xenograft mice. Overexpression of IDH1-R132H increased the expression of HIF-1α and downregulation of HIF-1α suppressed IDH1-R132H-induced effect on GBM. Reactive oxygen species (ROS) level was increased by IDH1-R132H over expression and the use of antioxidant inhibited IDH1-R132H-induced increase of HIF-1α expression. FAT Atypical Cadherin 1 (FAT1) expression was increased by IDH1-R132H over expression. Knockdown of FAT1 blocked IDH1-R132H-induced reduction of tumor growth in xenograft mice. Down regulation of FAT1 decreased HIF-1α expression and inhibited IDH1-R132H-induced increase of ROS level. Conclusions: Our findings provide new insights into IDH1-R132H-regulated downstream signaling in GBM and highlight the importance of IDH1-R132H-FAT1-ROS-HIF-1α signaling pathway in potential therapeutic intervention of GBM.

Pancreatic cancer is a malignant tumor of the digestive system with occult onset, low early diagnosis rate, rapid progression and poor prognosis. Perineural invasion (PNI) of pancreatic cancer is considered as an important factor which leads to the poor prognosis of pancreatic cancer. Neural invasion models of pancreatic cancer can simulate the occurrence and development of neural invasion of pancreatic cancer under the complex tumor microenvironment, which is an important carrier to study the molecular mechanism, early diagnosis and treatment improvement of PNI of pancreatic cancer. The current PNI model could be broadly divided into in vivo model and in vitro model, and in vivo model could further be divided into ectopic model and in situ model. Recently, based on the in vivo and in vitro models, genetically engineered mouse models and patient-derived xenograft models have been applied. Here, the preparation methods, clinical uses and limitations of the commonly used neural invasion in vitro and in vivo models of pancreatic cancer are reviewed.

Background: A growing number of studies have identified that circular RNAs (circRNAs) play a vital role in the progression of various tumors. However, the underlying functions and mechanisms of circRNAs in cervical cancer have not been clarified. Methods: qRT-PCR was used to detect the level of circGSE1 in cervical cancer tissues and matched normal tissues. In vitro cell wound healing, transwell migration and invasion assays were employed to assess the effects of circGSE1 on cell mobility. The pull-down, luciferase reporter, RIP and rescue assays were performed to evaluate the interaction between circGSE1and miR-138-5p and the regulation of miR-138-5p on Vimentin. Results: We found that circGSE1 was significantly higher in cervical cancer tissues than that in matched normal tissues. Further analyses revealed that the level of circGSE1 was positively correlated with tumor differentiation, FIGUREO stage, depth of stromal invasion, lymph node metastasis and infiltration of parauterine organ. Kaplan-Meier survival analysis showed that high circGSE1 predicted worse overall survival and disease-free survival. Down-regulated circGSE1 evidently inhibited cell migration and metastasis of cervical cancer, while up-regulated circGSE1 significantly promoted cell migration and metastasis. The pull-down, luciferase reporter and RIP assays revealed that circGSE1 directly bound to and sponge miR-138-5p. MiR-138-5p inhibited the expression of Vimentin through directly binding to 3'UTR of Vimentin mRNA. In addition, miR-138-5p suppressed cell migration and invasion through inhibiting Vimentin expression, and circGSE1 promoted cell migration and invasion through sponging miR-138-5p and enhancing Vimentin expression. Conclusion: CircGSE1 promotes the progression and may act as a novel diagnostic biomarker for disease progression of cervical cancer.

目的 探讨磁共振扩散张量成像(DTI)对原发性肝癌及肝转移瘤的诊断价值.方法 回顾性分析郑州大学附属肿瘤医院2016年1—12月收治、经病理学诊断证实为原发性肝癌或肝转移瘤的42例病人的磁共振成像(MRI)与DTI资料,统计其各向异性分数(FA)值及平均扩散系数(ADC)值,分析两者在不同类型疾病中的差异性.结果 不同疾病类型的FA值和ADC值有所不同,其中FA值自高而低分别为食管癌肝转移瘤(0.641±0.054)、胰腺癌肝转移瘤(0.602±0.064)、肺癌肝转移瘤(0.525±0.103)、肝癌(0.488±0.041)、直肠癌肝转移瘤(0.301±0.077)和胆囊癌肝转移瘤(0.284±0.059),各个类型之间的差异均有统计学意义(P<0.05);ADC值自高而低分别为胰腺癌肝转移瘤(1.95±0.21)×10-3 mm2/s、结直肠癌肝转移瘤(1.81±0.17)×10-3mm2/s、肝癌(1.68±0.17)×10-3 mm2/s、食管癌肝转移瘤(1.52±0.21)×10-3 mm2/s、肺癌肝转移瘤(1.44±0.14)×10-3 mm2/s、胆囊癌肝转移瘤(1.22±0.09)×10-3 mm2/s,各个类型之间的差异均有统计学意义(P<0.05).结论 肝脏MRI与DTI序列联合检测可获得较全面的信息,有助于肝癌及肝转移瘤的诊断和鉴别诊断.