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Review Article Open Access
Metabolomic Characteristics and Clinical Implications in Pathological Subtypes of Lung Cancer
Weixin Chen, Yuan Xu, Hongsheng Liu
Published online June 30, 2025
Cancer Screening and Prevention. doi:10.14218/CSP.2025.00005
Abstract
Lung cancer remains the leading cause of cancer-related mortality worldwide, with marked phenotypic differences observed among its major histological subtypes, adenocarcinoma (ADC), [...] Read more.

Lung cancer remains the leading cause of cancer-related mortality worldwide, with marked phenotypic differences observed among its major histological subtypes, adenocarcinoma (ADC), squamous cell carcinoma (SCC), and small cell lung cancer (SCLC), in both clinical presentation and therapeutic response. In recent years, metabolomics has emerged as a powerful tool for studying cancer metabolic reprogramming, providing new insights into the metabolic distinctions among lung cancer subtypes. This review summarizes recent research advances in the metabolomics of ADC, SCC, and SCLC. Studies have revealed that ADC and SCC display distinct metabolic profiles in lipid metabolism, amino acid metabolism, and cell membrane synthesis, while SCLC demonstrates a unique metabolic pattern. Through metabolomic technologies, particularly mass spectrometry and liquid chromatography, it is possible to effectively differentiate lung cancer subtypes and identify potential biomarkers for early diagnosis and personalized treatment. This review also explores the clinical potential of metabolomics in lung cancer, emphasizing its critical role in early diagnosis and subtype stratification. These methodological advances establish a robust foundation for precision oncology paradigms in thoracic malignancies.

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Original Article Open Access
Centrifugation Liver Support Using Regional Mesylate Anticoagulation is Safe for Liver Failure Patients with High Risk of Bleeding
Xin-Fang Zhu, Hong-Yuan Xue, Fei Sun, Qi Zhang, Bing-Yao Wang, Quan-Bao Zhang, Rui-Dong Li, Jian-Ming Zheng, Rong Xia
Published online March 17, 2025
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00036
Abstract
Patients with acute liver failure (ALF) or acute-on-chronic liver failure (ACLF) are at high risk of bleeding with traditional artificial liver support systems. To address the bleeding [...] Read more.

Patients with acute liver failure (ALF) or acute-on-chronic liver failure (ACLF) are at high risk of bleeding with traditional artificial liver support systems. To address the bleeding risk in liver failure patients, the safety of regional mesylate anticoagulation (RMA) in centrifugation artificial liver support systems (cALSS) is proposed for study.

In this prospective single-arm study, ALF and ACLF patients were treated with cALSS using RMA. Coagulation function was monitored, and the predictors of mesylate dose were analyzed using the area under the curve (AUC). Blood ammonia, model for end-stage liver disease scores, and survival rates at 28 and 90 days were assessed.

All 57 patients showed no new bleeding within 24 h post-cALSS. Most disseminated intravascular coagulation indicators improved at 0.5 h and 24 h post-cALSS. Thromboelastography showed hypocoagulability at 0.5 h post-cALSS. Univariate and multivariate analyses identified pre-R and pre-MA as key factors for R exceeding 10 m at 0.5 h post-cALSS, with odds ratios of 0.91 (95% confidence interval (CI): 0.84–0.98) and 2.03 (95% CI: 1.05–3.90), respectively, P < 0.05. The predictive values were pre-MA ≤ 38 mm (AUC = 0.817, 95% CI [0.690–0.907], P < 0.001) and pre-R > 6.3 m (AUC = 0.790, 95% CI [0.661–0.888], P < 0.001). Patients showed improvements in blood ammonia and model for end-stage liver disease scores after the last session, especially those with high initial levels (>80 µmol/L and >30). The 28-day and 90-day survival rates of ALF patients were similar to those of ACLF patients.

cALSS with RMA is safe for liver failure patients with a high risk of bleeding. Adjusting the mesylate dose based on pre-R and pre-MA enhances safety.

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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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Original Article Open Access
FTO Promotes Hepatocellular Carcinoma Progression by Mediating m6A Modification of BUB1 and Targeting TGF-βR1 to Activate the TGF-β Signaling Pathway
Lin Zhang, Li Gan, Yuru Lin, Zhechuan Mei, Shengtao Liao
Published online April 18, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00007
Abstract
Fat mass and obesity-associated protein (FTO) has been linked to various cancers, though its role in hepatocellular carcinoma (HCC) remains unclear. This study aimed to investigate [...] Read more.

Fat mass and obesity-associated protein (FTO) has been linked to various cancers, though its role in hepatocellular carcinoma (HCC) remains unclear. This study aimed to investigate FTO expression, its clinical relevance, functional role in HCC progression, and the underlying molecular mechanisms.

Quantitative reverse-transcription polymerase chain reaction and immunohistochemical analysis were used to assess FTO expression in HCC. Functional assays, including proliferation, invasion, and epithelial-mesenchymal transition studies, were conducted using HCC cell lines with FTO knockdown. N6-methyladenosine (m6A) RNA immunoprecipitation and RNA stability assays further elucidated the role of FTO in BUB1 mRNA methylation and stability. Co-immunoprecipitation studies were employed to confirm the interaction between BUB1 and TGF-βR1. In vivo studies in nude mice were conducted to evaluate tumor growth following FTO knockdown.

FTO was significantly upregulated in HCC tissues compared to normal liver tissues, with higher expression observed in advanced tumor-node-metastasis stages and metastatic HCC. Elevated FTO correlated with poor overall survival in patients. Silencing FTO decreased HCC cell proliferation, colony formation, invasion, epithelial-mesenchymal transition, and tumor growth in nude mice. Mechanistically, FTO downregulation led to increased m6A modification of BUB1 mRNA, thereby promoting its degradation via the YTH domain family 2-dependent pathway and reducing BUB1 protein levels. Additionally, BUB1 physically interacted with TGF-βR1, activating downstream TGF-β signaling.

FTO is overexpressed in HCC and is associated with poor clinical outcomes. Mechanistically, FTO promotes HCC progression by stabilizing BUB1 mRNA through an m6A-YTH domain family 2–dependent pathway, which activates TGF-β signaling. Targeting the FTO–BUB1–TGF-βR1 regulatory network may offer a promising therapeutic strategy for HCC.

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Case Report Open Access
Angiosarcoma as Homologous Mesenchymal Component of Ovarian Malignant Mixed Mullerian Tumor: A Case Study
Serena Wong, Natalia Buza, Pei Hui
Published online May 26, 2025
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2025.00005
Abstract
Malignant mixed Müllerian tumor (MMMT) or carcinosarcoma of the female genital tract is a rare but highly aggressive malignancy. We report a unique case of primary ovarian [...] Read more.

Malignant mixed Müllerian tumor (MMMT) or carcinosarcoma of the female genital tract is a rare but highly aggressive malignancy.

We report a unique case of primary ovarian MMMT with poorly differentiated angiosarcoma as its homologous sarcomatous component in a 53-year-old woman with a known germline BRCA1 mutation who presented with a pelvic mass. She underwent staging cytoreduction surgery including total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and pelvic and para-aortic lymph node dissections. The removed right ovarian tumor formed a 2.5 cm nodular to cystic mass replacing the entire organ. Microscopic examination revealed two distinct tumor components: high-grade serous carcinoma and poorly differentiated angiosarcoma. The proliferating sarcomatous cells were diffusely positive for CD31 and Factor VIII, but were negative for 100, SOX10 and cytokeratin. Both the serous carcinoma and angiosarcoma components demonstrated aberrant strong and diffuse p53 nuclear positivity. KRAS mutation analysis revealed guanine-adenine-thymine point mutation at codon 12 in both tumor components. Metastatic tumor was found involving the contralateral left ovary with the cellular composition of pure angiosarcomatous component.

This is the first report of an ovarian MMMT with angiosarcoma as its homologous sarcoma component. The presence of aberrant p53 expression and identical KRAS mutation in both the serous carcinoma and angiosarcoma components supports the theory of malignant mesenchymal transition/metaplasia in the development of MMMT.

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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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Original Article Open Access
Thyroid-stimulating Hormone and Thyroid Hormones in Women with Breast Cancer: Effects of Neoadjuvant Chemotherapy and Menopausal Status
María Jesús Ramírez-Expósito, María Pilar Carrera-González, Cristina Cueto-Ureña, José Manuel Martínez-Martos
Published online March 19, 2025
Oncology Advances. doi:10.14218/OnA.2024.00033
Abstract
The development and progression of breast cancer may be influenced by thyroid hormone levels. In this study, we investigated thyroid function in pre- and postmenopausal women with [...] Read more.

The development and progression of breast cancer may be influenced by thyroid hormone levels. In this study, we investigated thyroid function in pre- and postmenopausal women with breast cancer, with and without neoadjuvant chemotherapy (NCh).

The study included 198 women diagnosed with infiltrating ductal carcinoma: 83 did not receive NCh (39 premenopausal and 44 postmenopausal), while 115 underwent NCh before surgery (63 premenopausal and 52 postmenopausal). Additionally, 78 healthy volunteers, aged 28 to 69 years, served as the control group. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3) were quantified using chemiluminescent immunoassays.

We observed a significant increase in serum TSH and fT4 levels in both pre- and postmenopausal women with breast cancer, regardless of NCh treatment, compared to control subjects. However, postmenopausal women with breast cancer who received NCh showed lower fT4 levels than their untreated counterparts. Notably, fT3 levels increased only in premenopausal women with breast cancer who underwent NCh, compared to both the premenopausal control group and untreated premenopausal breast cancer patients.

Altered thyroid function was observed in both pre- and postmenopausal women with breast cancer, characterized by increased TSH and fT4 levels. Neoadjuvant chemotherapy appeared to attenuate the rise in fT4 levels in postmenopausal women while elevating fT3 levels in premenopausal women. These findings highlight the importance of monitoring thyroid hormone profiles in women with breast cancer, considering menopausal status, given their potential influence on tumor progression and chemotherapy effectiveness.

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Review Article Open Access
Protein Induced by Vitamin K Absence or Antagonist II in Primary Liver Cancer: Basic Research Insights and Clinical Applications
Xin Zhang, Rong Wang, Bin Niu, Liaoyun Zhang
Published online October 28, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00377
Abstract
Hepatocellular carcinoma (HCC) is the most common subtype of primary liver cancer and continues to be a major cause of cancer-related mortality, particularly in regions of China [...] Read more.

Hepatocellular carcinoma (HCC) is the most common subtype of primary liver cancer and continues to be a major cause of cancer-related mortality, particularly in regions of China with a high hepatitis B virus prevalence. Early-stage diagnosis remains challenging due to its asymptomatic onset and the limited sensitivity of conventional biomarkers, which together contribute to delayed detection, suboptimal therapeutic outcomes, and poor prognosis. These limitations underscore the urgent need for reliable, sensitive, and specific biomarkers to enable timely detection and targeted intervention. Protein induced by vitamin K absence or antagonist-II, an abnormal prothrombin variant generated under vitamin K deficiency or antagonism, has emerged as a promising candidate with diagnostic and therapeutic relevance in HCC. This review critically examines the molecular and biological characteristics of protein induced by vitamin K absence or antagonist-II, evaluates its clinical utility in HCC diagnosis and management, and delineates the current limitations hindering its broader application. Furthermore, future perspectives are proposed to guide translational research and clinical implementation. Collectively, this review aims to provide a comprehensive theoretical framework to advance precision diagnosis and individualized treatment strategies for HCC.

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Original Article Open Access
Upper Gastrointestinal Manifestations in Adult Egyptian Patients with Ulcerative Colitis: A Cross-sectional Study
Omar Elwakil, Reda Elwakil, Waleed Abdel-Aty Hamed, Ola Hassan Nada, Amal Saad-Hussein, Dalia Ghoraba, Ethar M Badran
Published online March 19, 2025
Journal of Translational Gastroenterology. doi:10.14218/JTG.2025.00001
Abstract
This study investigates upper gastrointestinal tract (UGIT) involvement in patients with ulcerative colitis (UC), a condition traditionally considered limited to the colon. Although [...] Read more.

This study investigates upper gastrointestinal tract (UGIT) involvement in patients with ulcerative colitis (UC), a condition traditionally considered limited to the colon. Although extra-colonic manifestations of UC are well recognized, UGIT issues have received less attention. This research aimed to document the clinical, endoscopic, and histopathological UGIT findings in adults with UC and assess their association with disease severity and extent.

This descriptive cross-sectional study was conducted at Ain Shams University over one year. A total of 78 UC patients underwent comprehensive clinical evaluations, including assessments of gastrointestinal complaints, medication history, disease progression, surgeries, and physical examinations. Endoscopic assessments of both the UGIT and colon were performed, accompanied by biopsies for histopathological analysis.

The study population had a mean age of 35.26 years, with a nearly equal gender distribution. Endoscopic findings revealed significant UGIT involvement: 64% of patients had esophagitis and/or gastroesophageal reflux disease, 93% had gastritis, and 80% had duodenitis. Histopathological findings showed notable inflammation, basal cell hyperplasia, and ulcerations in the esophagus, with 51.3% of patients exhibiting chronic gastritis and 38.5% testing positive for Helicobacter pylori infection. Statistical analysis demonstrated a strong association between colonic disease severity and UGIT endoscopic (p < 0.0001 and p < 0.001 in the esophagus and stomach, respectively) and histopathological (p < 0.004, p < 0.001, and p <0.005 in the esophagus, stomach, and duodenum, respectively) findings, particularly in patients with UGIT symptoms.

This study concludes that UGIT endoscopic and histopathological changes are prevalent among Egyptian UC patients, suggesting a significant link between UC and these UGIT findings.

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Original Article Open Access
Diagnostic Performance of ATR-FTIR Spectroscopy in Discriminating Normal Breast Tissue and Breast Tumors
Samuel T. Adeleke, Christopher Igbeneghu, Sina Iyiola
Published online May 26, 2025
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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