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Research Letter Open Access
Development and Validation of a Novel Noninvasive Model to Predict Liver Fibrosis Staging in Untreated Patients with Chronic Hepatitis B
Jianhua Hu, Xiaoli Zhang, Zhibo Zhou, Fangfang Geng, Hongyu Jia, Linfeng Jin, Weixiang Zhong, Guodong Yu, Xue Wen, Hainv Gao, Yida Yang
Published online July 7, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00175
Original Article Open Access
ATOX1 Promotes Hepatocellular Carcinoma Carcinogenesis via Activation of the c-Myb/PI3K/AKT Signaling Pathway
Qin Ouyang, Siyu Jia, Qianyu Zhu, Yanmeng Li, Huaduan Zi, Sisi Chen, Pingping He, Hengcheng Tang, Yanling Li, Anjian Xu, Bei Zhang, Xiaomin Wang, Xiaojuan Ou, Donghu Zhou, Jian Huang
Published online July 7, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00422
Abstract
Despite advancements in diagnostic and therapeutic strategies, hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality. Antioxidant-1 (ATOX1) has been [...] Read more.

Despite advancements in diagnostic and therapeutic strategies, hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality. Antioxidant-1 (ATOX1) has been implicated in oncogenic processes across various cancer types; however, its specific role in HCC remains unclear. This study aimed to investigate the function of ATOX1 and its underlying molecular mechanisms in HCC.

Immunohistochemical analysis was conducted to assess ATOX1 expression in HCC tissues. Cell Counting Kit-8, colony formation, Transwell migration, flow cytometry, and reactive oxygen species (ROS) assays were employed to evaluate the malignant behaviors of tumor cells. A xenograft mouse model was employed to assess the effects of ATOX1 knockdown on tumor growth in vivo. DCAC50 treatment was performed to inhibit the copper transport function of ATOX1. RNA sequencing was conducted to explore the potential molecular mechanisms of ATOX1 in HCC.

ATOX1 expression was significantly elevated in HCC tumor tissues. ATOX1 promoted cell proliferation, colony formation, and migration. Knockdown of ATOX1 suppressed tumor growth in vivo. Mechanistically, ATOX1 activated c-Myb, and thus enhanced the malignant phenotype of HCC cells via activation of the PI3K/AKT signaling pathway. Additionally, ATOX1 reduced intracellular copper accumulation and inhibited ROS production and apoptosis. Inhibition of ATOX1 by DCAC50 decreased cell proliferation while increasing ROS levels and apoptosis in HCC cells. Notably, acetylcysteine reversed the reduction in c-Myb expression induced by ATOX1 knockdown.

ATOX1 may promote HCC carcinogenesis through the activation of the c-Myb/PI3K/AKT pathway and the inhibition of copper accumulation and oxidative stress.

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Original Article Open Access
Cumulative Hepatitis B Surface Antigen/Hepatitis B Virus DNA Ratio in Immune-tolerant Hepatitis B Patients: A 10-year Follow-up Study
Dawu Zeng, Yanfang Huang, Sheng Lin, Naling Kang, Yanxue Lin, Jiaji Jiang, Yueyong Zhu, Qi Zheng, Jiming Zhang
Published online July 4, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00205
Abstract
Patients with chronic hepatitis B virus (HBV) infection in the immune-tolerant phase may still experience hepatic inflammation and disease progression, and could benefit from early [...] Read more.

Patients with chronic hepatitis B virus (HBV) infection in the immune-tolerant phase may still experience hepatic inflammation and disease progression, and could benefit from early antiviral treatment. This study aimed to investigate changes in the cumulative hepatitis B surface antigen (HBsAg)/HBV DNA ratio in immune-tolerant patients during the transition to the immune-active phase, and to evaluate its potential in predicting the risk of disease progression.

This longitudinal study included 127 untreated immune-tolerant patients, who were followed for up to 10 years. An independent cohort of 109 subjects was retrospectively enrolled for external validation. The relationship between the cumulative HBsAg/HBV DNA ratio and the duration of immune tolerance or transition to the immune-active phase was examined. The predictive value of the ratio was assessed and validated.

The relationship between the cumulative HBsAg/HBV DNA ratio and disease progression risk showed a non-linear pattern: below a ratio of 1.791, the risk of disease progression decreased rapidly as the ratio increased; above 1.791, the risk plateaued. The area under the curve for predicting disease progression was 0.67, 0.64, and 0.85 for cumulative HBsAg, HBV DNA, and the HBsAg/HBV DNA ratio, respectively. Multivariable Cox regression analysis revealed the cumulative HBsAg/HBV DNA ratio as an independent predictor of disease progression, with higher ratios associated with a lower risk. Prediction models incorporating this ratio were developed and externally validated, demonstrating strong performance and clinical utility.

The cumulative HBsAg/HBV DNA ratio is an independent factor influencing the duration of immune tolerance and shows superior predictive performance. It may serve as a valuable marker for assessing the risk of disease progression in patients with chronic HBV infection.

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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.

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Original Article Open Access
Clinical, Microbiological, and Antibiotic Treatment Characteristics of Bacterial Infections in Patients with Liver Cirrhosis in China: A Multicenter Study
Xiuding Zhang, Haoda Weng, Qinzhi Deng, Min Deng, Xuwei Wu, Zuxiong Huang, Shourong Liu, Rui Wu, Chunlian Ma, Yao Xu, Jianfeng Zhong, Jie Yang, Yinxia Wu, Huajiang Shen, Feng Ding, Fang Wang, Xuezhen Zhai, Chunxian Peng, Haotang Ren, Jie Jin, Xiangfei Xu, Xiaofei Li, Xiaoting Ye, Guoqing Qian, Shuilin Sun, Xuebing Yao, Haifeng Miao, Qianggu Xiao, Shaoheng Ye, Qing Zhang, Xinyi Xu, Xia Yu, Yue Yu, Yan Lan, Huilan Tu, Xianbin Xu, Xinrong Zhang, Rui Huang, Xiaohan Qian, Qiao Yang, Jifang Sheng, Yu Shi
Published online July 3, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00211
Abstract
Epidemiological data on bacterial infections in cirrhosis in China remain limited. Therefore, we aimed to conduct a multicenter study to investigate the characteristics and outcomes [...] Read more.

Epidemiological data on bacterial infections in cirrhosis in China remain limited. Therefore, we aimed to conduct a multicenter study to investigate the characteristics and outcomes of patients with cirrhosis and bacterial infections in China.

We retrospectively enrolled 1,438 hospitalized adult patients with cirrhosis and bacterial or fungal infections from 24 hospitals across China between January 2018 and September 2024. Data on demographics, clinical features, microbiology, treatment, and outcomes were collected.

A total of 1,783 infection episodes were recorded, including 1,668 first infections and 115 second infections. Most infections were community-acquired (86.6%). Pneumonia was the most common infection type (26.7%), followed by spontaneous bacterial peritonitis (19.5%) and spontaneous bacteremia (14.1%). Among 754 pathogens isolated from 620 patients, Klebsiella pneumoniae (20.1%) was nearly as common as Escherichia coli (21.7%). Multidrug-resistant (MDR) organisms accounted for 41.0% of all isolates, with extended-spectrum β-lactamase-producing Escherichia coli being the most prevalent MDR strain (8.9% of patients). Adherence to empirical antibiotic treatment guidelines from the European Association for the Study of the Liver was significantly lower in this cohort compared to the global study (21.5% vs. 61.2%, P < 0.001), accompanied by a lower clinical resolution rate (63.5% vs. 79.8%, P < 0.001).

The clinical and microbiological characteristics of bacterial infections in patients with cirrhosis in China differ substantially from those reported in other regions. These findings highlight the need for region-specific management and prevention strategies, particularly in light of the changing microbiological landscape, high MDR prevalence, and suboptimal antibiotic practices.

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Review Article Open Access
The Link Between Immune Aging and Type 2 Diabetes: A Review of Mechanisms and Implications
Swarup K. Chakrabarti, Dhrubajyoti Chattopadhyay
Published online July 1, 2025
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2025.00018
Abstract
Type 2 diabetes (T2D) is a metabolic disorder characterized by insulin resistance (IR), inflammation, and dysregulation in glucose metabolism. The disease is spreading globally, [...] Read more.

Type 2 diabetes (T2D) is a metabolic disorder characterized by insulin resistance (IR), inflammation, and dysregulation in glucose metabolism. The disease is spreading globally, partly due to aging, which can damage the immune system and speed up the progression of the metabolic disorder. This review primarily delves into the triggers for T2D within the framework of the ominous octet, which emphasizes 8 principal factors under the “ominous octet” framework that contribute to high blood glucose and associated metabolic disorders. The article studies the interplay of hyperinsulinemia, mitochondrial dysfunction (MD), and endoplasmic reticulum (ER) stress with immune aging in driving disease progression affecting each component of the octet. MD and ER stress can result in defects in insulin signaling, ultimately leading to β-cell death. Chronic inflammation associated with aging, also known as inflammaging, especially affects older adults by worsening IR and glucose regulation, which creates a continuous sequence of metabolic problems. Thus, the “ominous octet” framework provides fundamental knowledge to develop personalized treatment approaches that target metabolic dysfunction together with ER stress, MD, and immune system imbalances. These strategies show promising potential to improve treatments for T2D and may lead to better health outcomes for older adults dealing with this condition.

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Review Article Open Access
Polygenic Architecture of Dental Caries: Single Nucleotide Polymorphisms in Genetic Epidemiology
Luiz Alexandre Chisini, Luana Carla Salvi, Rodrigo Varella de Carvalho, Francine dos Santos Costa, Flávio Fernando Demarco, Marcos Britto Correa
Published online July 1, 2025
Gene Expression. doi:10.14218/GE.2025.00018
Abstract
This review presents the latest evidence on the link between genetic single nucleotide polymorphisms and dental caries, highlighting key genes and pathways involved, introducing [...] Read more.

This review presents the latest evidence on the link between genetic single nucleotide polymorphisms and dental caries, highlighting key genes and pathways involved, introducing foundational concepts, and discussing essential methodological considerations for future research. Several genes have been identified as significantly associated with caries experience, including those related to tooth mineral tissues, taste perception, salivary composition and flow, and immune response. Epistatic interactions appear to be crucial in explaining genetic influence. Inconsistencies in the literature are attributed to variations in caries classification, age groups, ethnic backgrounds, limited statistical power, and linkage disequilibrium. Population stratification often confounds results, and few studies adequately control for genetic ancestry. Ensuring Hardy-Weinberg equilibrium and accounting for linkage disequilibrium are essential to avoid bias. Bonferroni corrections for multiple comparisons are fundamental but rarely applied, contributing to inconsistent findings. In conclusion, genetic epidemiology studies suggest that dental caries has a genetic component, accounting for significant individual differences in disease risk.

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Original Article Open Access
Disrupted Connectivity of the Brainstem Ascending Reticular Activating System Nuclei-left Parahippocampal Gyrus Could Reveal Mechanisms of Delirium Following Basal Ganglia Intracerebral Hemorrhage
Jun Zhang, Pengfei Fu, Qiang Yuan, Weijian Yang, Zhuoyin Du, Meihua Wang, Xiangru Ye, Gang Wu, Jin Hu
Published online June 30, 2025
Neurosurgical Subspecialties. doi:10.14218/NSSS.2025.00030
Abstract
Delirium, commonly observed in critically ill patients following intracerebral hemorrhage (ICH), is an acute neuropsychiatric disorder characterized by disturbances in attention, [...] Read more.

Delirium, commonly observed in critically ill patients following intracerebral hemorrhage (ICH), is an acute neuropsychiatric disorder characterized by disturbances in attention, consciousness, and cognition. The underlying brain network mechanisms remain poorly understood. This study aimed to explore the functional connectivity (FC) of the ascending reticular activating system (ARAS) in delirium patients with basal ganglia ICH and to identify potential biomarkers for predicting delirium onset.

In this cross-sectional study, brain networkomics techniques were used to examine the FC within the ARAS in ICH patients with and without delirium. A two-sample t-test compared differences in ARAS connectivity between delirium and non-delirium groups, identifying abnormal brain regions and their corresponding FC values. Receiver operating characteristic curve analysis was then performed to evaluate the predictive value of FC for delirium onset.

A significant disruption in FC between the brainstem ARAS nuclei and the left parahippocampal gyrus was observed in ICH patients with delirium. The FC strength between these regions was a reliable predictor of delirium occurrence, with an area under the curve of 0.893, indicating high predictive accuracy.

The disruption of FC between the brainstem ARAS nuclei and the left parahippocampal gyrus may represent a key mechanism underlying delirium pathogenesis. The strength of this connectivity could serve as a potential biomarker for predicting delirium onset. Future research should focus on strategies to restore this connectivity as a potential treatment for early reversal of delirium.

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Original Article Open Access
Opportunities and Challenges of Multimodal Electroencephalography and Functional Near Infrared Spectroscopy in Neurological Disorders: A Bibliometric Analysis from 2005 to 2024
Nan Wang, Juanning Si, Yifang He, Sipeng Zhu, Xiaoke Chai, Tianqing Cao, Qiheng He, Yitong Jia, Yi Yang, Jizong Zhao
Published online June 30, 2025
Neurosurgical Subspecialties. doi:10.14218/NSSS.2025.00020
Abstract
Multimodal applications combining electroencephalogram (EEG) and functional near-infrared spectroscopy (fNIRS) are widely used in cognitive neuroscience and have progressively been [...] Read more.

Multimodal applications combining electroencephalogram (EEG) and functional near-infrared spectroscopy (fNIRS) are widely used in cognitive neuroscience and have progressively been applied to clinical applications, such as the joint diagnosis of amyotrophic lateral sclerosis, Alzheimer’s disease, and pediatric epilepsy. This study conducted a bibliometric analysis of EEG-fNIRS synchronization techniques over the past 20 years. The aim was to clarify their diagnostic and therapeutic value in clinical applications, particularly in the neurological system, and to guide future research and development trends.

This study utilized the Web of Science Core Collection database to analyze documents published between January 1, 2005, and May 13, 2024. CiteSpace and VOSviewer were employed for visual analyses of co-author relationships, keywords, citation patterns, and journal distributions. By overlaying dual-map diagrams and analyzing annual publication trends, the study identified research hotspots, development trends, and the evolution of EEG-fNIRS technology.

A total of 645 articles and reviews from 55 countries were analyzed. The USA contributed the most publications. The team led by Michela Balconi at the Catholic University of the Sacred Heart published the highest number of papers. Frontiers in Human Neuroscience had the greatest number of publications, while NeuroImage had the highest citation impact. Recent research has primarily focused on the application of neuroimaging and neurophysiological techniques (e.g., EEG, fNIRS, functional magnetic resonance imaging), brain activation, and brain-computer interface.

This study highlights the applications and developmental trends of dual-modality EEG-fNIRS technology. Specifically, this approach can assist in diagnosing neurological disorders, assessing activation and connectivity within functional brain regions, and evaluating therapeutic neuromodulation in clinical neurology. Overall, multimodal fusion is poised to advance neuroscience research significantly.

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Consensus Open Access
The Second Beijing Consensus on Holistic Integrative Medicine for the Management of Helicobacter pylori-associated “Disease-Syndrome”
Guibin Yang, Shuo Feng, Jianxiang Liu, Fulian Hu, The National Consensus Group on Holistic Integrative Medicine for the Management of Helicobacter pylori-associated “Disease-Syndrome”
Published online June 30, 2025
Cancer Screening and Prevention. doi:10.14218/CSP.2025.00009
Abstract
Helicobacter pylori (H. pylori) infection plays a pivotal role in gastric carcinogenesis and poses a significant burden on global public health. Eradicating H. pylori infection [...] Read more.

Helicobacter pylori (H. pylori) infection plays a pivotal role in gastric carcinogenesis and poses a significant burden on global public health. Eradicating H. pylori infection is an important strategy for the primary prevention of gastric cancer but remains a challenge. This consensus, an update of The First Beijing Consensus on Holistic Integrated Medicine (HIM) Combining Traditional Chinese with Western Medicine for the Management of Helicobacter pylori-associated “Disease-Syndrome” released in 2018, aims to further incorporate the HIM perspective and the latest research advances into the management of H. pylori-associated “disease-syndrome”. Forty-three experts from 29 medical institutions were selected to vote and reach a consensus. The consensus consists of five sections addressing 19 key questions with corresponding statements. These cover the current status and challenges of managing H. pylori infection in China, refractory H. pylori infection, the role of HIM in H. pylori management, holistic and individualized assessment/treatment for refractory infections, and the integration of traditional Chinese medicine in treating H. pylori-associated “disease-syndrome”. Finally, three therapeutic schemes for traditional Chinese medicine in treating H. pylori-associated “disease-syndrome” were proposed. Taken together, this consensus incorporates the principles of HIM along with advanced medical knowledge and clinical practice into individualized treatment strategies. It is recommended as a guideline for the management of H. pylori-associated “disease-syndrome” in China.

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