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Original Article Open Access
Adjuvant Chemotherapy Improves Survival in Resected Early-onset Pancreatic Cancer after Neoadjuvant Therapy: A Retrospective Cohort Study Based on the SEER Database
Ning Pu, Taochen He, Wenchuan Wu, Hanlin Yin, Joseph R. Habib, Qiangda Chen, Zhihang Xu, Zhenlai Jiang, Yun Jin, Wenhui Lou, Liang Liu
Published online June 6, 2025
Oncology Advances. doi:10.14218/OnA.2025.00008
Abstract
The incidence of early-onset pancreatic cancer (EOPC) is rising, yet optimal treatment strategies remain unclear. While adjuvant chemotherapy (ACT) has shown survival benefits in [...] Read more.

The incidence of early-onset pancreatic cancer (EOPC) is rising, yet optimal treatment strategies remain unclear. While adjuvant chemotherapy (ACT) has shown survival benefits in pancreatic ductal adenocarcinoma, its specific role in EOPC patients following neoadjuvant chemotherapy (NACT) and surgery remains underexplored. This study aimed to assess the clinical benefit of ACT in EOPC patients after NACT.

This retrospective cohort study analyzed pancreatic ductal adenocarcinoma patients from the SEER database (2006–2019) who received NACT followed by curative resection. Propensity score matching (1:1) was used to balance covariates such as tumor, lymph node, metastasis stage, chemotherapy, and radiotherapy. Overall survival (OS) and cancer-specific survival (CSS) were compared between patients with EOPC (<50 years) and average-onset pancreatic cancer (AOPC, ≥50 years). Multivariate Cox regression analysis was performed to identify prognostic factors.

After propensity score matching (124 EOPC vs. 124 AOPC), EOPC patients had significantly longer median OS (41.0 vs. 29.0 months, P = 0.042) and CSS (48.0 vs. 30.0 months, P = 0.016). ACT was an independent prognostic factor for EOPC (OS: hazard ratio = 0.495, 95% confidence interval 0.271–0.903, P = 0.022; CSS: hazard ratio = 0.419, 95% confidence interval 0.219–0.803, P = 0.009), but not for AOPC (P > 0.05). Subgroup analysis revealed that EOPC patients with tumor, lymph node, metastasis stage II disease or those receiving ACT derived the greatest survival benefit.

EOPC patients exhibit superior survival following NACT and surgical resection compared to AOPC, with ACT further enhancing outcomes in this subgroup. These findings support the use of tailored ACT for EOPC and underscore the need for prospective validation.

Full article
Review Article Open Access
Folate-biopterin Crosstalk in Human Disease
Mark D. Lucock, Robert J. Leeming
Published online July 4, 2025
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2025.00020
Abstract
The importance of putative folate-biopterin metabolic interactions lies in the role they may play in the expression of several clinically relevant phenotypes. However, to date, [...] Read more.

The importance of putative folate-biopterin metabolic interactions lies in the role they may play in the expression of several clinically relevant phenotypes. However, to date, clinical studies on folate-biopterin interactions have been limited. The purpose of this article was to highlight the close relationship between these two cofactors, which share structural similarities and exhibit overlapping metabolic pathways. This folate-biopterin crosstalk has generated several ideas and hypotheses that are critical to advancing the biochemical understanding of several important and seemingly disparate clinical and/or biologically important phenotypes. These phenotypes include melanization/pigmentation, phenylketonuria, autism, neural tube defects, affective disorders, and vascular disease. This review provides a timely, integrated overview of this important area of biochemistry, which is under-represented in the literature and would benefit from further scientific and clinical investigation using improved metabolite-specific analytical methodologies applied to clinically relevant questions.

Full article
Review Article Open Access
Decoding High-grade Endometrial Cancer: A Molecular-histologic Integration using the Cancer Genome Atlas Framework
Himani Kumar, Akansha Deshwal, Sneha Datwani, Zaibo Li
Published online July 21, 2025
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2025.00021
Abstract
High-grade endometrial carcinoma (HGEC) is an aggressive tumor with increasing incidence and mortality. Traditional classifications, such as Bokhman’s dualistic model and the World [...] Read more.

High-grade endometrial carcinoma (HGEC) is an aggressive tumor with increasing incidence and mortality. Traditional classifications, such as Bokhman’s dualistic model and the World Health Organization histopathological system, have limitations due to tumor heterogeneity and interobserver variability. This review provides a comprehensive understanding of how integrating histopathological and molecular data, particularly The Cancer Genome Atlas (TCGA) classification, advances risk stratification and personalized treatment in HGEC. It highlights current challenges and identifies future directions to improve diagnostic accuracy and patient outcomes through precision medicine.

A literature review was conducted focusing on the epidemiology, histopathology, and molecular profiling of HGEC, with an emphasis on TCGA and next-generation sequencing studies.

TCGA molecular classification stratifies HGEC into four subgroups with distinct prognoses which includes POLE-ultramutated (POLE), microsatellite instability hypermutated, copy number high and copy number low. The next-generation sequencing enhances diagnostic precision and guides personalized treatment. However, diagnostic challenges persist in clinical practice.

Integrating histopathology with TCGA-based molecular profiling refines HGEC classification, enabling improved risk stratification and targeted therapies. Continued efforts to improve diagnostic accuracy are essential to advance patient care.

Full article
Review Article Open Access
Emerging Serum Biomarkers for Chronic Hepatitis B: Focus on Serum HBV RNA and HBcrAg
Yike Tian, Haibo Yu, Juan Chen
Published online July 22, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00064
Abstract
Chronic hepatitis B virus (HBV) infection remains a major cause of liver diseases, including cirrhosis and hepatocellular carcinoma. Reliable biomarkers for assessing viral replication, [...] Read more.

Chronic hepatitis B virus (HBV) infection remains a major cause of liver diseases, including cirrhosis and hepatocellular carcinoma. Reliable biomarkers for assessing viral replication, liver damage, and predicting clinical outcomes are essential for effective patient management. This review focuses on two promising biomarkers: serum HBV RNA and hepatitis B core-related antigen, both of which show strong correlations with viral replication and disease progression. Serum HBV RNA levels reflect the quantity and transcriptional activity of intrahepatic covalently closed circular DNA, providing insights into viral replication. They also correlate with other markers of replicative activity and have predictive value for key clinical outcomes, including hepatitis B e antigen and hepatitis B surface antigen seroconversion, relapse after therapy cessation, and liver fibrosis. Similarly, hepatitis B core-related antigen is closely associated with covalently closed circular DNA levels, correlates with markers of viral replication, and shows promise in predicting liver fibrosis, cirrhosis, and the risk of hepatocellular carcinoma. This review highlights the potential of both biomarkers for monitoring disease progression and guiding therapeutic decisions, particularly in the context of personalized treatment strategies and risk assessment for liver-related complications.

Full article
Original Article Open Access
Prognostic and Clinicopathological Significance of circPVT1 in Solid Tumors: A Systematic Review and Meta-analysis
Menglan Li, Kai Qian, Zhixian Zhu, Yajing Deng, Pengfei Li
Published online April 30, 2025
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00042
Abstract
circPVT1 has emerged as a key regulator in disease progression and clinical outcomes. However, its prognostic relevance and association with clinicopathological parameters in solid [...] Read more.

circPVT1 has emerged as a key regulator in disease progression and clinical outcomes. However, its prognostic relevance and association with clinicopathological parameters in solid malignancies remain to be fully elucidated. To address this, we conducted a meta-analysis to elucidate the clinical significance of circPVT1 in solid tumors.

A comprehensive literature search was conducted across multiple databases, including PubMed, Web of Science, Embase, the Cochrane Library, and CNKI, with a cutoff date of December 31, 2024. Statistical analyses were conducted using STATA 12.0 to calculate pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs), assessing the impact of circPVT1 expression on overall survival (OS) and its association with clinicopathological characteristics.

This analysis included 27 clinical studies encompassing a total of 2,219 patients. Elevated circPVT1 expression was significantly associated with poorer OS in patients with solid tumors (HR = 1.68, 95% CI: 1.39–2.02, P < 0.001). This association was particularly notable in lung cancer (HR = 2.08, 95% CI: 1.51–2.88, P < 0.001) and osteosarcoma (HR = 1.65, 95% CI: 1.38–1.97, P < 0.001), with similar trends observed in hepatocellular carcinoma, colorectal cancer, and papillary thyroid carcinoma. Furthermore, the increased circPVT1 level was correlated with larger tumor size (OR = 1.36, 95% CI: 1.11–1.67, P = 0.004), lymph node metastasis (OR = 1.56, 95% CI: 1.22–2.00, P < 0.001), distant metastasis (OR = 1.80, 95% CI: 1.10–2.92, P = 0.017), and advanced tumor-node-metastasis stage (OR = 1.84, 95% CI: 1.50–2.25, P < 0.001).

Aberrant circPVT1 expression is associated with adverse OS and unfavorable clinicopathological features in solid tumors, underscoring its potential utility as a prognostic biomarker and indicator of tumor aggressiveness.

Full article
Original Article Open Access
Interrater Reliability of the Nancy Histologic Index in Assessing Histologic Remission in Treated Ulcerative Colitis Biopsies: A Multi-institutional Experience Among Gastrointestinal Pathologists in the United States
Krithika D. Shenoy, Jiannan Li, Daniela Allende, Samuel J. Ballentine, Kathleen Byrnes, Parakkal Deepak, Alicia G. Dessain, Ashwini K. Esnakula, Raul S. Gonzalez, Xianyong Gui, Hwajeong Lee, Jingmei Lin, Shivani Mattay, Namrata Setia, Hanlin L. Wang, Zhaohai Yang, Xuchen Zhang, Xiuli Liu, on behalf of the SPARC-IBD Investigators
Published online June 26, 2025
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2025.00022
Abstract
Histologic remission is recommended as an adjunctive treatment target in ulcerative colitis, and scoring systems have been proposed to enhance reproducibility. The Nancy Histologic [...] Read more.

Histologic remission is recommended as an adjunctive treatment target in ulcerative colitis, and scoring systems have been proposed to enhance reproducibility. The Nancy Histologic Index (NHI) is increasingly used in clinical trials; however, its performance in real-world settings is not fully established. This study aimed to assess the interrater reliability (IRR) of the NHI among gastrointestinal pathologists in the United States.

Thirty-seven whole-slide images of colorectal biopsies from 34 treated ulcerative colitis patients enrolled in a multicenter adult cohort were independently reviewed by 12 gastrointestinal pathologists. Each biopsy was reviewed twice, five months apart, and graded using the NHI. Prior to the second review, pathologists completed an online tutorial on the NHI.

The NHI showed substantial IRR in both reviews [intraclass correlation coefficient (ICC) = 0.79; 95% confidence interval (CI), 0.70–0.87 at Review 1; ICC = 0.78; 95% CI, 0.69–0.86 at Review 2]. However, considerable variability was observed in individual grade assignments, with the lowest IRR for Grade 2 (ICC = 0.24; 95% CI, 0.15–0.37; P < 0.001, and ICC = 0.23; 95% CI, 0.14–0.36; P < 0.001 for Reviews 1 and 2, respectively), followed by Grade 4 (ICC = 0.41; 95% CI, 0.29–0.55; P < 0.001, and ICC = 0.47; 95% CI, 0.35–0.61; P < 0.001). Grade 1 showed the highest IRR (ICC = 0.79; 95% CI, 0.70–0.87; P < 0.001, and ICC = 0.78; 95% CI, 0.69–0.86; P < 0.001). When Grades 2, 3, and 4 (i.e., active disease) were grouped together, the IRR remained substantial across both reviews (ICC = 0.76; 95% CI, 0.66–0.85; P < 0.001).

While the substantial IRR for active disease (Grades ≥ 2) in this study underscores the clinical utility of the NHI, refinement of criteria for Grades 2, 3, and 4 will be crucial in reducing variability among observers and enabling more accurate monitoring of treatment endpoints.

Full article
Letter to the Editor Open Access
Review Article Open Access
Safflower Yellow Pigments in Coronary Heart Disease: Mechanisms, Applications, and Future Perspectives
Lu Dong, Xi-Mei Zhang, Jian Chen, Yi-Xin Zhang, Shi-Jun Yue
Published online June 27, 2025
Future Integrative Medicine. doi:10.14218/FIM.2025.00016
Abstract
Coronary heart disease is an ischemic condition characterized by vascular stenosis or obstruction caused by coronary atherosclerosis, resulting in myocardial ischemia, hypoxia, [...] Read more.

Coronary heart disease is an ischemic condition characterized by vascular stenosis or obstruction caused by coronary atherosclerosis, resulting in myocardial ischemia, hypoxia, or necrosis. It is one of the leading causes of death in both urban and rural populations in China. Safflower yellow pigments, the main active components of the traditional Chinese herbal medicine safflower, are primarily composed of quinochalcone compounds, including hydroxysafflor yellow A and anhydrosafflor yellow B—of which hydroxysafflor yellow A is the principal component. Studies have demonstrated that these pigments can improve myocardial ischemia, reduce ischemia-reperfusion injury, alleviate atherosclerotic damage, and address risk factors associated with coronary heart disease. This review aimed to systematically and comprehensively summarize the mechanisms of action of safflower yellow pigments and their active components in the context of coronary heart disease and its related risk factors.

Full article
Letter to the Editor Open Access
Original Article Open Access
Biomarker Discovery for Metabolic Dysfunction-associated Steatotic Liver Disease Utilizing Mendelian Randomization, Machine Learning, and External Validation
Gong Feng, Giovanni Targher, Christopher D. Byrne, Na He, Man Mi, Yi Liu, Hongbin Zhu, Ming-Hua Zheng, Feng Ye
Published online July 16, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00270
Abstract
The causal biomarkers for metabolic dysfunction-associated steatotic liver disease (MASLD) and their clinical value remain unclear. In this study, we aimed to identify biomarkers [...] Read more.

The causal biomarkers for metabolic dysfunction-associated steatotic liver disease (MASLD) and their clinical value remain unclear. In this study, we aimed to identify biomarkers for MASLD and evaluate their diagnostic and prognostic significance.

We conducted a Mendelian randomization analysis to assess the causal effects of 2,925 molecular biomarkers (from proteomics data) and 35 clinical biomarkers on MASLD. Mediation analysis was performed to determine whether clinical biomarkers mediated the effects of molecular biomarkers. The association between key clinical biomarkers and MASLD was externally validated in a hospital-based cohort (n = 415). A machine learning–based diagnostic model for MASLD was developed and validated using the identified molecular biomarkers. Prognostic significance was evaluated for both molecular and clinical biomarkers.

Six molecular biomarkers—including canopy FGF signaling regulator 4 (CNPY4), ectonucleoside triphosphate diphosphohydrolase 6 (ENTPD6), and major histocompatibility complex, class I, A (HLA-A)—and eight clinical biomarkers (e.g., serum total protein (STP)) were identified as causally related to MASLD. STP partially mediated the effect of HLA-A on MASLD (23.61%) and was associated with MASLD in the external cohort (odds ratio = 1.080, 95% confidence interval: 1.011–1.155). A random forest model demonstrated high diagnostic performance (AUC = 0.941 in training; 0.875 in validation). High expression levels of CNPY4 and ENTPD6 were associated with the development of and poorer survival from hepatocellular carcinoma. Low STP (<60 g/L) predicted all-cause mortality (HR = 2.50, 95% confidence interval: 1.22–5.09).

This study identifies six causal molecular biomarkers (e.g., CNPY4, ENTPD6, HLA-A) and eight clinical biomarkers for MASLD. Notably, STP mediates the effect of HLA-A on MASLD and is associated with all-cause mortality.

Full article
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