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Review Article Open Access
Zhicheng Yang, Yongle Zhao, Honglin Chen, Han Zhang, Maoting Tan, Xianliu Li, Lingling Tao, Hongyun Zhao
Published online July 29, 2025
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00124
Abstract
Actively identifying the risk factors and predictive indicators associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) can enable early diagnosis and treatment, which [...] Read more.

Actively identifying the risk factors and predictive indicators associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) can enable early diagnosis and treatment, which is of great significance for prolonging the survival of patients with LC. Hemodynamic disturbances, advanced LC, vascular endothelial injury, and mutations in thrombophilic genetic factors are established risk factors for PVT-LC. Venous dilatation and decreased blood flow velocity contribute to hemodynamic disturbances. The severity of LC can be assessed by the degree of portal hypertension, liver metabolic function biomarkers, and validated liver scoring systems. Iatrogenic interventions, endotoxemia, and metabolic syndrome may induce vascular endothelial injury and hypercoagulability, the latter of which can be quantified via coagulation-anticoagulation-fibrinolysis biomarkers. Mutations in thrombophilic genetic factors, such as Factor V Leiden, MTHFR C667T, and JAK2 V617F, disrupt coagulation-anticoagulation homeostasis and predispose patients to PVT-LC. This review specifically focuses on comprehensively delineating established risk factors and predictive indicators for PVT-LC, thereby providing a theoretical foundation for the construction of clinically applicable PVT predictive models to guide early interventions and improve the prognosis. Future research should further validate the associations between recently proposed risk factors and PVT-LC, while simultaneously establishing cutoff values for indicators with robust predictive value to construct a clinically applicable PVT prediction framework.

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Original Article Open Access
Silpa Choday, Anne Jarvis, William Graham, Paul Kang, Justin Reynolds
Published online August 1, 2025
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Journal of Translational Gastroenterology. doi:10.14218/JTG.2025.00019
Abstract
While metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with obesity, the cause of its rapidly rising prevalence is not well understood. In this study, [...] Read more.

While metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with obesity, the cause of its rapidly rising prevalence is not well understood. In this study, we aimed to examine the association between arsenic exposure and MASLD in humans.

Urinary inorganic arsenic data from the National Health and Nutrition Examination Survey, 2011–2020, were used. These were combined with death certificate data from the National Death Index of the National Center for Health Statistics to ascertain mortality rates. Weighted linear regression and chi-squared analysis were performed.

The analysis included 6,386 participants after exclusions. The mean urinary arsenic level was 5.92 µg/L in participants with MASLD versus 5.59 µg/L in those without. Alanine aminotransferase levels exhibited a statistically significant increasing trend across both continuous arsenic levels and arsenic quintiles. A statistically significant upward trend was observed for the income-to-poverty ratio and body mass index but not for education status. MASLD prevalence was highest among the white population, while an increasing trend was observed in the Hispanic population over the years (p < 0.001). The proportion of Mexican Americans increased to 12.6% in the MASLD group versus 8.09% in the non-MASLD cohort (p < 0.001). There was a statistically significant increase in the odds of MASLD across arsenic exposure levels, with individuals in the highest quintile having a 32% greater likelihood compared to those in the lowest quintile (p-trend = 0.002). The odds further increased to 55% in the highest quintile (odds ratio 1.55, 95% confidence interval: 1.19–2.03; p-trend < 0.001). MASLD was more prevalent in females than males (57.9% vs. 47.6%; p < 0.001), and the mean age increased from 46.9 years to 49.9 years (p = 0.016).

Our findings reveal a positive association between urinary arsenic exposure and MASLD, with increasing trends particularly observed among Hispanics and those with higher income-to-poverty ratios and body mass index.

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Original Article Open Access
Sellappan Mohan, Arumugam Nagarajan
Published online November 11, 2024
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Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2023.00005
Abstract
The polymer’s slow hydrolysis facilitates the sustained release of the immunogen, stabilizing the antigen encapsulated within the microspheres. As a result, microspheres ranging [...] Read more.

The polymer’s slow hydrolysis facilitates the sustained release of the immunogen, stabilizing the antigen encapsulated within the microspheres. As a result, microspheres ranging from 40 µm to 70 µm in diameter can be formed. This innovative microsphere formulation allows for efficient uptake by macrophages and other antigen-presenting cells. This study aimed to use biocompatible polymethyl methacrylate microspheres for the controlled delivery of antigens.

The potency of various formulations containing encapsulated tetanus toxoid (TT) with polymethyl methacrylate polymer microspheres was assessed using the toxin neutralization and challenge methods. The neutralization test was conducted on pooled sera two weeks after the initial immunization and weekly for four weeks following the booster dose administration. Scanning electron micrographs of the microspheres revealed drug leaching from spherical granular matrices.

The injection site showed a higher distribution of smaller microparticles, resulting in depot release. The polymer coating’s thickness was significantly lower compared to the 25% polymer microspheres. Concentrations ranging from 0.00024 mL to 0.00030 mL caused significant tetanic paralysis. Two weeks after the initial immunization, the antigenic activity of TT was below the minimum threshold, possibly due to insufficient levels of antigenic TT within the system within seven days post-immunization. The polymethacrylate microsphere elicited a notable immune response, but only the polymer concentration of 25% w/v met the I.P. requirements; lower polymer concentrations were ineffective.

The polymer’s slow hydrolysis facilitates the sustained release of the immunogen, stabilizing the antigen encapsulated within microspheres. Consequently, microspheres ranging from 40 µm to 70 µm in diameter can be assembled. This innovative microsphere formulation allows for efficient uptake by macrophages and other antigen-presenting cells.

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Original Article Open Access
Samuel T. Adeleke, Christopher Igbeneghu, Sina Iyiola
Published online May 26, 2025
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Cancer Screening and Prevention. doi:10.14218/CSP.2025.00004
Abstract
Histopathology is the gold standard in cancer diagnosis. However, attenuated total reflectance (ATR)-Fourier transform infrared (FTIR) spectroscopy has shown diagnostic potential [...] Read more.

Histopathology is the gold standard in cancer diagnosis. However, attenuated total reflectance (ATR)-Fourier transform infrared (FTIR) spectroscopy has shown diagnostic potential in other settings. Therefore, this study aimed to investigate the sensitivity and specificity of the ATR-FTIR spectroscopy in evaluating breast lesions.

This study was conducted on formalin-fixed, paraffin-embedded biopsy blocks received at Ladoke Akintola University of Technology Teaching Hospital between 2022 and 2023. The blocks were categorized into 10 normal (from benign breast tissue), 15 benign, and 31 malignant samples. Tissue sections of 15 µm were obtained during block trimming and floated onto FTIR slides. An additional 4 µm tissue sections were stained with hematoxylin and eosin for tumor diagnosis and to identify suitable areas on the FTIR slide. Spectrometer readings were taken within the range of 4,000–600 cm−1, 32 scans, and 16 cm−1 resolution, using the average of 10 preprocessed spectra per slide. Biomarkers were calculated by ratioing peak intensities for A1632/A1543, A1632/A2922, A1632/A1080, A1080/A1543, A1237/A1080, and A1043/A1543, which represent protein, diagnostic marker, cytoplasm-nucleus ratio, carcinogenesis marker, phosphate, and glycogen, respectively. The receiver operating characteristic curve was used to determine sensitivity, specificity, and the area under the curve (AUC).

The AUC analysis showed that cytoplasm-nucleus ratio values of 0.99 and 0.95 effectively distinguished normal from malignant tissue, and benign from malignant tissue, respectively (p < 0.0001). Additionally, protein marker (AUC = 0.73), diagnostic marker (AUC = 0.85), and cytoplasm-nucleus ratio marker (AUC = 0.94) were able to discriminate normal from benign tissue. Overall, the receiver operating characteristic analysis showed 100% sensitivity and specificity ranging from 54% to 87%. Glycogen (AUC = 1.00) exhibited 100% sensitivity in discriminating fibroadenoma from fibrocystic changes.

ATR-FTIR spectroscopy demonstrates high diagnostic accuracy in differentiating normal, benign, and malignant breast tissues using specific spectral biomarkers. Among these, the cytoplasm-nucleus ratio marker showed strong potential as a reliable spectral indicator for distinguishing various types of breast tumors. The cytoplasm-nucleus ratio marker demonstrated strong potential as a reliable spectral indicator for distinguishing various types of breast tumors.

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Original Article Open Access
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
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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
Ebrahim Hesam, Sahar Fouladi, Mohammad Ali Zeyghami, Somayeh Rahimi, Sara Hosseinzadeh, Abolfazl Amini
Published online March 25, 2025
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Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2024.00033
Abstract
Epileptogenesis involves complex mechanisms, including inflammation and apoptosis. Rosiglitazone, a peroxisome proliferator-activated receptor gamma agonist, possesses anti-inflammatory [...] Read more.

Epileptogenesis involves complex mechanisms, including inflammation and apoptosis. Rosiglitazone, a peroxisome proliferator-activated receptor gamma agonist, possesses anti-inflammatory and neuroprotective properties. This study investigated whether rosiglitazone can prevent pentylenetetrazole (PTZ)-induced kindling in mice by modulating inflammatory cytokines and apoptosis pathways.

Male C57BL/6 mice (n = 8 per group) were assigned to sham, control, or rosiglitazone-treated groups. Kindling was induced with intraperitoneal PTZ (40 mg/kg) every 48 h for 17 days. Rosiglitazone (0.1 mg/kg) was administered 30 m before each PTZ injection. Seizure progression was monitored, and hippocampal tissues were analyzed via immunohistochemistry and Western blotting to assess cytokine levels (interleukin (IL)-10, IL-17A, tumor necrosis factor-alpha, interferon-gamma), caspase-3 activity, and glial fibrillary acidic protein expression.

Rosiglitazone significantly delayed seizure progression, reduced seizure scores, and lowered pro-inflammatory cytokine levels (IL-17A, tumor necrosis factor-alpha, interferon-gamma) while increasing IL-10. Immunohistochemical analysis revealed fewer caspase-3-positive cells and reduced glial fibrillary acidic protein expression in the treatment group compared to controls.

Rosiglitazone exerts neuroprotective effects in PTZ-induced kindling, likely through its anti-inflammatory and anti-apoptotic actions. These findings underscore its potential as a therapeutic agent for mitigating epileptogenesis, warranting further investigation in combination therapies and clinical trials.

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Mini Review Open Access
Yongfeng Lu, Caihong Liu, Cheng Jiang, Chuan Xu
Published online December 25, 2024
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Oncology Advances. doi:10.14218/OnA.2024.00030
Abstract
Liquid biopsy (LB) represents a promising strategy for the early diagnosis and treatment of lung cancer. However, relying solely on single-biomarker immunohistochemistry for predictive [...] Read more.

Liquid biopsy (LB) represents a promising strategy for the early diagnosis and treatment of lung cancer. However, relying solely on single-biomarker immunohistochemistry for predictive purposes has shown limited efficacy, often leading to suboptimal responses in certain patients. LB provides a complementary or alternative approach to immunohistochemistry by aiding in the identification of patients better suited for immunotherapy, thereby improving treatment precision. This review highlights key LB targets, including circulating tumor cells, exosomes, and small protein molecules, and explores the predictive and prognostic value of LB in immunotherapy for lung cancer and other tumors. These biomarkers play complex and multifaceted roles in liquid biopsies. Consequently, researchers have developed numerous targeted detection methods to study and identify key factors among multiple biomarkers in lung cancer and other tumor diseases. In addition, the limitations and future directions of LB are examined, aiming to advance its clinical application and support the development of personalized and precise immunotherapy. The integration of LB with artificial intelligence holds significant clinical potential for guiding immunotherapy and advancing precision medicine in lung cancer and other tumors.

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Original Article Open Access
Vijaya Kadam Maruthi, Tong Sun
Published online August 18, 2025
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Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2025.00023
Abstract
High-grade serous carcinoma is a rare diagnosis in cervical biopsies. Cervical serous carcinoma is no longer recognized as a primary cervical tumor in the 2020 World Health Organization [...] Read more.

High-grade serous carcinoma is a rare diagnosis in cervical biopsies. Cervical serous carcinoma is no longer recognized as a primary cervical tumor in the 2020 World Health Organization classification. This study aimed to characterize the clinicopathologic, immunohistochemical, and molecular features of high-grade serous carcinoma identified in cervical or endocervical biopsies, to assess tumor origin and ensure accurate classification.

Fifty-nine cases originally diagnosed as “serous carcinoma” or “high-grade serous carcinoma” in cervical or endocervical biopsies from 2013 to 2023 were retrospectively reviewed. Clinical data, radiologic findings, and follow-up information were analyzed. Histologic features and immunohistochemical profiles were re-evaluated. Targeted next-generation sequencing was performed on a subset of cases.

The majority of tumors (96%) were determined to originate from the endometrium (n = 47) or the tubo-ovarian region (n = 4), with only one case confirmed as a primary cervical carcinoma. Morphologic patterns varied and could mimic human papillomavirus-associated adenocarcinoma. All tumors showed aberrant p53 expression and diffuse p16 positivity. WT-1 was expressed in all tubo-ovarian tumors but in only 12% of endometrial cases. Estrogen receptor and progesterone receptor were frequently positive in endometrial tumors; human epidermal growth factor receptor 2 was positive in 31% of cases. Molecular analysis confirmed tumor protein p53 mutations and other alterations typical of uterine serous carcinoma.

High-grade serous carcinoma identified in cervical biopsies is overwhelmingly secondary to upper genital tract tumors, most commonly of endometrial origin. A small subset of endocervical adenocarcinomas may mimic serous carcinoma. These findings support the exclusion of primary cervical serous carcinoma from the current World Health Organization classification and emphasize the importance of accurate diagnosis for appropriate management.

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Review Article Open Access
Liangjin Zhang, Zhiqiang Zhang, Jiale He, Zhiheng Zhang, Huaixiang Zhou, Youheng Jiang, Xin Zhong, Yanming Yang, Ningning Li, Wu Xu, Yulong He, Qunlong Jin
Published online July 30, 2025
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Oncology Advances. doi:10.14218/OnA.2025.00014
Abstract
Glioblastoma (GBM) is the most prevalent and aggressive form of primary brain malignancy in adults. Despite continuous advancements in standard treatment modalities, the prognosis [...] Read more.

Glioblastoma (GBM) is the most prevalent and aggressive form of primary brain malignancy in adults. Despite continuous advancements in standard treatment modalities, the prognosis for patients remains extremely poor, with a median survival of less than two years. In recent years, chimeric antigen receptor T-cell (CAR-T) therapy has achieved revolutionary success in hematologic malignancies, marking a significant breakthrough in the field of immunotherapy. However, the successful application of CAR-T therapy to GBM still faces dual challenges: antigen heterogeneity and the immunosuppressive tumor microenvironment. This review systematically summarizes these challenges encountered in CAR-T therapy for GBM and the innovative strategies currently under development to address these challenges, providing insights for the future clinical translation of CAR-T therapy in GBM.

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Original Article Open Access
Miaomiao Li, Meng Shi, Changyi Ji, Luyu Wang, Ze Xiang, Ying Wang, Hongtao Wang, Mengmeng Gu, Runing Ji, Jian Wu
Published online May 26, 2025
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00111
Abstract
Gut dysbiosis has been reported in severe liver diseases. However, information on the impact of hepatitis E virus infection on the gut microbiota, and the association between enteric [...] Read more.

Gut dysbiosis has been reported in severe liver diseases. However, information on the impact of hepatitis E virus infection on the gut microbiota, and the association between enteric microbiota disturbances and acute hepatitis E (AHE), is limited, particularly in elderly patients with AHE (AHE-elderly). Our objective was to characterize the AHE-specific microbiome in elderly patients and evaluate its association with clinical outcomes.

Fecal samples and clinical data were collected from 58 AHE-elderly patients (46 self-healing cases, 12 non-self-healing cases) and 30 elderly patients with healthy controls (hereinafter referred to as HCs-elderly). Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Bioinformatic analyses, including alpha diversity and STAMP, were performed. The predictive potential of Bacteroides fragilis was assessed using statistical analysis and receiver operating characteristic curves.

Alpha diversity indices showed no significant differences in microbial diversity between the AHE-elderly and HCs-elderly groups, nor between self-healing and non-self-healing groups among AHE-elderly patients. Nevertheless, a trend toward altered species richness was observed. In the AHE-elderly group, the relative abundance of Firmicutes, Lactobacillales, and Bacilli increased significantly. Meanwhile, compared with the self-healing group, Bacteroidetes were more abundant in the non-self-healing group. At the species level, Bacteroides fragilis was the most abundant in the non-self-healing group, significantly contributing to the divergence in gut microbiota between the two groups.

The relative abundance of Bacteroidetes significantly distinguished AHE-elderly patients from healthy controls and could more accurately predict recovery outcomes in elderly AHE patients. These findings suggest new strategies for preventing and managing AHE recurrence in the elderly patients.

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