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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.

Full article
Review Article Open Access
World Health Organization Reporting System for Soft Tissue Cytopathology: A Concise Review with a Practical Diagnostic Approach
Marilyn M. Bui
Published online June 24, 2025
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2025.00016
Abstract
Soft tissue cytopathology plays a vital role in the diagnosis and management of soft tissue neoplasms, necessitating a standardized classification system to improve diagnostic accuracy [...] Read more.

Soft tissue cytopathology plays a vital role in the diagnosis and management of soft tissue neoplasms, necessitating a standardized classification system to improve diagnostic accuracy and guide clinical decision-making. This article provides a concise review of the World Health Organization (WHO) Reporting System for Soft Tissue Cytopathology and presents a practical diagnostic approach to soft tissue cytopathology.

The WHO Reporting System is reviewed in conjunction with relevant literature. The reporting system employs a six-category framework: non-diagnostic, benign, atypical, soft tissue neoplasm of uncertain malignant potential, suspicious for malignancy, and malignant. Each category is associated with a corresponding risk of malignancy and recommended clinical management guidelines. This classification aligns with the WHO Classification of Soft Tissue and Bone Tumours (5th edition) and incorporates cytomorphologic features, ancillary studies, and clinical correlation to enhance diagnostic reproducibility and communication among pathologists and clinicians.

The system supports a probabilistic approach to risk stratification, enabling more consistent diagnostic and therapeutic strategies.

As molecular diagnostics and immunocytochemistry continue to advance, this framework provides a robust foundation for the interpretation of soft tissue fine-needle aspiration biopsies and optimized patient care.

Full article
Review Article Open Access
Potential of Phytomedicine in Benefiting Both Long COVID and Acute Coronary Syndromes: A State-of-the-art Review
Xiao Jiang, Yiran Lu, Yu Ding, Yuanyuan Liu, Zhen Zhao, Peizhong Liu, Chuangpeng Li, Song He, Qing Zhang, Rongyuan Yang, Qing Liu
Published online April 30, 2025
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00043
Abstract
Acute coronary syndrome (ACS) in patients with SARS-CoV-2 infection is primarily driven by inflammation-induced myocardial injury through both direct and indirect mechanisms. Effective [...] Read more.

Acute coronary syndrome (ACS) in patients with SARS-CoV-2 infection is primarily driven by inflammation-induced myocardial injury through both direct and indirect mechanisms. Effective clinical management requires a dual approach: addressing cardiovascular lesions while also mitigating virus-induced local and systemic inflammation. This comprehensive approach is essential for improving the diagnosis and treatment of SARS-CoV-2-associated ACS. Emerging evidence highlights the potential of myocardial protective agents, including angiotensin-converting enzyme 2-modulating drugs and traditional Chinese medicine, which not only stabilize plaques and improve endothelial function but also confer cardioprotective effects. Furthermore, advancements in nanotechnology offer promising strategies for targeted therapy—particularly through angiotensin-converting enzyme 2 receptor modulation—by enhancing the precision and efficacy of herbal medicine delivery. This review explores the complex interplay between SARS-CoV-2 infection and ACS pathogenesis, and evaluates the therapeutic potential of pharmacological, herbal, and nanotechnology-based interventions in managing this multifaceted condition.

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Editorial Open Access
Welcome to the New Era of Neurosurgical Subspecialization
Hong-Yang Zhao, Wai-Sang Poon
Published online March 30, 2025
Neurosurgical Subspecialties. doi:10.14218/NSSS.2025.00013
Original Article Open Access
The Development of a Risk Prediction Model to Predict Patients’ Likelihood of Completing Human Papillomavirus Vaccination
Amanda F. Petrik, Eric S. Johnson, Raj Mummadi, Matthew Slaughter, Matthew Najarian, Gloria D. Coronado
Published online December 25, 2024
Cancer Screening and Prevention. doi:10.14218/CSP.2024.00026
Abstract
Human papillomavirus (HPV) infection is the primary cause of cervical, anogenital, and oropharyngeal cancers in the United States. These cancers are preventable through HPV vaccination. [...] Read more.

Human papillomavirus (HPV) infection is the primary cause of cervical, anogenital, and oropharyngeal cancers in the United States. These cancers are preventable through HPV vaccination. Research is critically needed to identify effective strategies for promoting HPV vaccination among high-risk groups. This study develops a risk prediction model to identify patients who are unlikely to complete HPV vaccination, with the goal of using the model to direct resources and increase vaccination rates.

We assessed vaccination status along with patient, provider, and clinic characteristics that predict vaccination completion. We then developed a predictive model to assess the likelihood of completing HPV vaccination, which can be used to target interventions based on patient needs. We used a retrospective cohort from a large integrated delivery system in Oregon. Using logistic regression with data available in the electronic health record, we created a risk model to determine the likelihood of vaccination completion among patients aged 11–17 years.

In a cohort of 61,788 patients, 40,570 (65.7%) had received at least one dose of the HPV vaccine. The full model included 17 demographic, clinical, provider, and community characteristics, achieving a bootstrap-corrected C-statistic of 0.67 with adequate calibration. The reduced model, which retained five demographic and clinical characteristics (age, language, race, ethnicity, and prior vaccinations), had a bootstrap-corrected C-statistic of 0.65 and adequate calibration.

Our findings suggest that a risk prediction model can guide the implementation of targeted interventions and the intensity of those interventions based on the likelihood of vaccination completion.

Full article
Original Article Open Access
Proteogenomic Analysis of Healthy and Cancerous Prostate Tissues Using SILAC and Mutation Databases
Giullia de Souza Santos, Rafaela Marie Melo da Cunha, Ricardo Alves da Silva, Thauan Costa da Silva, Thiago Antonio Costa do Nascimento, Lucas Marques da Cunha
Published online March 30, 2025
Oncology Advances. doi:10.14218/OnA.2024.00032
Abstract
Prostate cancer is the second most diagnosed cancer in men worldwide and a significant cause of cancer-related death. Proteogenomic analysis offers insights into how genomic mutations [...] Read more.

Prostate cancer is the second most diagnosed cancer in men worldwide and a significant cause of cancer-related death. Proteogenomic analysis offers insights into how genomic mutations influence protein expression and can identify novel biomarkers. This study aimed to investigate the impact of missense mutations on protein abundance in prostate cancer versus healthy tissues using SILAC-based quantitative proteomics.

Mass spectrometry data from prostate tumors and adjacent healthy tissues were analyzed using stable isotope labeling. Peptides were classified based on their abundance into RefSeq and Variant Abundant groups. Missense mutations were mapped via RefSeq and dbPepVar databases. Protein intensity metrics were compared, and Spearman’s correlation was used to evaluate the relationship between mutation presence and protein abundance.

Functional enrichment revealed that RefSeq Abundant proteins are involved in normal metabolic and structural functions, while Variant Abundant proteins are enriched in tumor-related pathways such as immune evasion and apoptosis suppression. A significant negative correlation was found between protein intensity difference and ratio (p < 0.05), indicating that missense mutations contribute to altered protein expression. Mutation hotspot analysis identified recurrent alterations in genes such as PPIF and ACTB. PROVEAN was used to evaluate the functional impact of variants, identifying several as deleterious to protein stability and function.

Missense mutations are associated with altered protein abundance and may promote oncogenic processes in prostate cancer. These findings enhance the understanding of genome-proteome interactions and could support the development of targeted biomarkers and therapies.

Full article
Original Article Open Access
Global Trends and Cross-country Inequalities of Acute Hepatitis E in the Elderly, 1990–2021: A Comprehensive Analysis
Deliang Huang, Jinyan Jiang, Jinghan Peng, Zhibin Zhu, Yuanyuan Chen, Siyu Zhang, Huiyi Lai, Hong Yu, Qi Zhao, Yanna Wu, Yanping Chen, Jun Chen
Published online May 30, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00101
Abstract
Acute hepatitis E (AHE) in the elderly can lead to severe complications including liver failure and mortality, yet the epidemiological landscape remains poorly characterized. This [...] Read more.

Acute hepatitis E (AHE) in the elderly can lead to severe complications including liver failure and mortality, yet the epidemiological landscape remains poorly characterized. This study aimed to assess the burden, trends, and health inequalities of AHE among the elderly over the past three decades, and to further predict its changes by 2030.

Data on AHE in the elderly were obtained from the Global Burden of Disease 2021. The burden of AHE was analyzed by trends, decomposition, cross-country inequalities, and predictive analysis.

In 2021, the global incidence and Disability-Adjusted Life Years (DALYs) for AHE among the elderly were recorded as 1,130,013.35 and 20,084.77, respectively. Although there were significant differences in the incidence and DALYs across countries, the number of incident cases increased from 1990 to 2021, with a slight rise in age-standardized rates, while the number and age-standardized rate of DALYs showed a declining trend. Decomposition analysis revealed that population growth and aging are the drivers of changes in incidence, while epidemiological changes somewhat offset the increases in DALYs driven by population growth. Low socio-demographic index countries bear a disproportionate burden of elderly AHE, although inequality gaps have narrowed over time. Notably, up to 2030, the number of incident cases and DALYs will continue increasing. The burden in elderly women was more pronounced than in men.

The burden of elderly AHE, as a major public health issue, remains substantial. While cross-country inequities have been alleviated over time, the pressure on lower socio-demographic index countries to control the disease remains high. AHE in elderly women requires further attention. This emphasizes the significant challenges faced in controlling and managing elderly AHE.

Full article
Research Letter Open Access
Complete Resolution of Refractory Ascites and Pleural Effusion with Sustained Improvement in Urinary Sodium Excretion in a Cirrhotic Patient Treated with Empagliflozin
Wei Qin, Yunyi Gao, Yuanyuan Zhao, Ning Bian, Weiguang Fan, Wei Wang, Yuan Gao, Zhongjie Hu
Published online June 19, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00172
Original Article Open Access
Inhibition of Postmenopausal Osteoporosis in Ovariectomized Mice by Huo Xue Tong Luo Capsule Using Network Pharmacology-based Mechanism Prediction and Pharmacological Validation
Qiangqiang Zhao, Feihong Che, Hongxiao Li, Rihe Hu, Liuchao Hu, Qiushi Wei, Liangliang Xu, Yamei Liu
Published online March 25, 2025
Future Integrative Medicine. doi:10.14218/FIM.2024.00049
Abstract
Huo Xue Tong Luo Capsule (HXTL) has been clinically used to treat osteonecrosis of the femoral head, osteoporosis, and other bone and joint diseases with promising effects. Our [...] Read more.

Huo Xue Tong Luo Capsule (HXTL) has been clinically used to treat osteonecrosis of the femoral head, osteoporosis, and other bone and joint diseases with promising effects. Our previous study has shown that HXTL can promote osteogenesis in mesenchymal stem cells by inhibiting lncRNA-Miat expression through histone modifications. However, the mechanism by which HXTL treats postmenopausal osteoporosis (PMOP) remains unclear. In this study, we used network pharmacology-based mechanism prediction, molecular docking, and pharmacological validation to investigate the mechanism of HXTL in treating PMOP.

The key candidate targets and relevant signaling pathways of HXTL for PMOP treatment were predicted using network pharmacology and molecular docking analysis. RAW264.7 cells were used for Western blot to validate the predicted mechanistic pathways. The ovaries of mice were surgically removed to simulate PMOP. The effect of HXTL on PMOP was evaluated using tartrate-resistant acid phosphatase staining and immunohistochemical assays in vivo.

Network pharmacology analysis suggested that HXTL interacted with 215 key targets linked to PMOP, primarily affecting the PI3K-AKT signaling pathway. Molecular docking showed that the main components of HXTL exhibited strong binding affinity to NFATc1, p-PI3K, and p-AKT1. Furthermore, our in vitro results confirmed that HXTL suppressed the PI3K-AKT signaling pathway. In vivo, HE and tartrate-resistant acid phosphatase staining results showed that HXTL inhibited osteoclast formation and protected bone mass.

This research demonstrated that HXTL could inhibit osteoclast formation and prevent bone loss induced by ovariectomy in mice by inhibiting the PI3K-AKT signaling pathway. These findings provide important evidence for the clinical application of HXTL in treating PMOP.

Full article
Original Article Open Access
Assessment of Metabolic Dysfunction-associated Steatotic Liver Disease and Liver Fibrosis: A Cross-sectional Study in Asymptomatic Individuals in Greater Vancouver
Nicholas W. Tjandra, David M.P. Di Fonzo, Tianyi Wen, Kirby Lau, Peter Kwan, Eric M. Yoshida, Daljeet Chahal
Published online June 23, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00109
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of hepatic fibrosis, yet its prevalence in asymptomatic populations remains unclear. This study [...] Read more.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of hepatic fibrosis, yet its prevalence in asymptomatic populations remains unclear. This study aimed to assess the prevalence of steatosis and significant fibrosis in asymptomatic individuals without known liver disease in the Greater Vancouver Area.

Interested individuals voluntarily registered online via the Canadian Liver Foundation website or by telephone. Inclusion criteria included age ≥ 19 years, no known liver disease, and low alcohol intake (<30 g/day for men, <20 g/day for women). Demographic and clinical data were collected, and all participants underwent transient elastography after a 3-h fast. The study aimed to collect 4,500 analyzable scans while reflecting the region’s ethnic diversity.

A total of 4,193 participants were analyzed. The median age was 62 years, the median body mass index was 25.4, and 45% were male. Asian individuals comprised 42% of the cohort. Steatosis was present in 59.6% of participants, and 45.7% met diagnostic criteria for MASLD. Significant fibrosis (F2–F4) was found in 8.6%. Age, male sex, ethnicity, cardiac disease, diabetes, hypertension, and obesity were significantly associated with fibrosis. Logistic regression analysis confirmed age, weight, diabetes, dyslipidemia, hypertension, and obesity as independent predictors.

A substantial proportion of asymptomatic individuals in Greater Vancouver have undetected MASLD and significant fibrosis. Early identification of high-risk groups may support broader implementation of transient elastography screening. This study provides one of the first North American population-based estimates of MASLD and fibrosis stratified by ethnicity, offering new insights into liver disease distribution among Caucasian, Chinese, and South Asian populations.

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