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Review Article Open Access
Advances in Novel Drug Therapy for Metabolic Dysfunction-associated Steatohepatitis Cirrhosis
Syed Alishan Nasir, Anjali Mangla, Vikas Taneja, Triston Berger, Deep Pandya, Vikas Gupta, Joseph K. Lim
Published online March 17, 2025
Journal of Translational Gastroenterology. doi:10.14218/JTG.2024.00040
Abstract
Metabolic dysfunction-associated steatotic liver disease has emerged as a leading cause of chronic liver disease and cirrhosis in the Western world. With rising rates of obesity, [...] Read more.

Metabolic dysfunction-associated steatotic liver disease has emerged as a leading cause of chronic liver disease and cirrhosis in the Western world. With rising rates of obesity, the prevalence of metabolic dysfunction-associated steatohepatitis (MASH)-related cirrhosis is expected to increase. MASH is associated with chronic hepatic inflammation and progressive liver fibrosis, and significant research is focused on developing pharmacological therapies to reverse these downstream complications. Recent trials have explored various therapeutic targets across metabolic, inflammatory, and fibrogenic pathways aimed at decreasing liver triglycerides, inflammation, lipotoxicity, and fibrosis. Some of these drugs show promise in reversing biomarkers and/or histologic markers of steatohepatitis and fibrosis, although most have been primarily studied in non-cirrhotic patients. However, in the context of the significant unmet medical need of patients with MASH-associated cirrhosis, growing interest in targeting compensated cirrhosis has prompted renewed investment in numerous early clinical and late-stage programs evaluating novel investigational agents in this population. This review summarizes current therapies under evaluation in phase 2 and 3 clinical trials for MASH-related cirrhosis, highlighting drug mechanisms, outcomes, and future research directions.

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Review Article Open Access
Molecular Testing of FLT3 Mutations in Hematolymphoid Malignancies in the Era of Next-generation Sequencing
Shunsuke Koga, Wei Du, Guang Yang, Linsheng Zhang
Published online March 30, 2025
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2025.00008
Abstract
FMS-like tyrosine kinase 3 (FLT3) mutations are among the most common genetic alterations in acute myeloid leukemia (AML) and play a pivotal role in leukemogenesis. The two primary [...] Read more.

FMS-like tyrosine kinase 3 (FLT3) mutations are among the most common genetic alterations in acute myeloid leukemia (AML) and play a pivotal role in leukemogenesis. The two primary mutation types, internal tandem duplications (ITDs) and tyrosine kinase domain point mutations, serve as key prognostic markers and therapeutic targets. Advances in next-generation sequencing (NGS) have revolutionized FLT3 mutation detection by providing precise insights into mutation architecture, enhancing risk stratification, and enabling personalized treatment strategies. Additionally, these advancements have facilitated molecular minimal residual disease (MRD) testing, which is instrumental in guiding post-remission management. This review summarizes the molecular characteristics, diagnostic approaches, and therapeutic implications of FLT3 mutations in hematologic malignancies.

A narrative review of the current literature on FLT3 mutations was conducted, incorporating data from original research articles, clinical trials, and recent reviews. Relevant studies were identified through a PubMed literature search and manually curated.

FLT3 mutations are detected in approximately 30% of AML cases and occur at lower frequencies in myelodysplastic syndromes, chronic myelomonocytic leukemia, acute lymphoblastic leukemia, and mixed phenotype acute leukemia. NGS enables comprehensive mutation profiling, revealing rare variants and subclonal complexity while supporting MRD detection with high analytic sensitivity. FLT3-ITD-based MRD positivity is strongly associated with relapse and poor survival in AML. Clinical trial data support FLT3 inhibitors, including midostaurin, gilteritinib, and quizartinib, in FLT3-mutated AML. Additionally, MRD-guided therapy and combination treatment strategies are promising approaches to overcoming resistance.

FLT3 mutations play a central role in the pathogenesis and treatment of AML and related malignancies. NGS-based testing and MRD monitoring transform clinical decision-making by refining risk stratification and enabling personalized therapeutic interventions. Establishing standardized testing protocols and the broader integration of FLT3-targeted therapies will be essential for optimizing patient outcomes.

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Review Article Open Access
The Emerging Role of Flavonoids in the Treatment of Type 2 Diabetes Mellitus: Regulating the Enteroendocrine System
Daifen Wen, Mingrui Li
Published online January 16, 2025
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00055
Abstract
Type 2 diabetes mellitus (T2DM) is a prevalent yet complex metabolic disorder that has shown a rising incidence over the past few decades. Recent research has identified flavonoids [...] Read more.

Type 2 diabetes mellitus (T2DM) is a prevalent yet complex metabolic disorder that has shown a rising incidence over the past few decades. Recent research has identified flavonoids as compounds capable of both preventing and managing T2DM through various mechanisms. These mechanisms include enhancing insulin sensitivity, stimulating insulin secretion, modulating intestinal microbiota, inhibiting glucose absorption, and reducing gluconeogenesis. Moreover, numerous studies have suggested that flavonoids may influence gut hormones. Therefore, we propose that flavonoids could serve as effective therapeutic agents for T2DM by modulating intestinal hormone levels. This review aimed to elucidate the potential pathways through which flavonoids may impact T2DM, with a particular emphasis on their role in regulating the enteroendocrine system.

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Review Article Open Access
Hyperuricemia: Current State and Prospects
Weizheng Zhang
Published online January 2, 2025
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00199
Abstract
Hyperuricemia (HU), characterized by elevated uric acid (UA) levels in the blood, is a global health concern associated with various conditions, including cardiovascular diseases, [...] Read more.

Hyperuricemia (HU), characterized by elevated uric acid (UA) levels in the blood, is a global health concern associated with various conditions, including cardiovascular diseases, gout, hypertension, metabolic syndrome, renal dysfunction, and neurodegenerative diseases. Recent studies highlight the multifaceted origins of HU, implicating genetic predisposition, dietary patterns, lifestyle choices, and environmental influences. Genetic variations affecting enzymes and transporters involved in purine metabolism and UA excretion have been identified, paving the way for personalized treatment strategies. Advances in diagnostic imaging and omics technologies provide enhanced precision in detecting and evaluating risks. While pharmacological interventions remain central to managing HU, persistent challenges such as treatment resistance necessitate the exploration of novel drug targets and lifestyle modifications. Chinese herbal medicines present a potential alternative with fewer side effects. Emerging research on the impact of gut microbiota on UA metabolism opens new therapeutic avenues. Despite progress, challenges such as optimizing treatment duration and understanding long-term effects remain. Collaborative efforts are essential to address these challenges and advance our comprehension of HU. Integrating precision medicine and holistic patient care approaches holds promise for improving outcomes and enhancing the quality of life for individuals with HU. This review provided a contemporary analysis of HU, covering its causes, associated health risks, diagnosis, treatment, and future outlook.

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Opinion Open Access
Original Article Open Access
Effectiveness and Safety of Tenofovir Amibufenamide in the Treatment of Chronic Hepatitis B: A Real-world, Multicenter Study
Yaping Li, Yongmei Lin, Guoe Gou, Dandan Cui, Xiaohong Gao, Guanghua Xu, Hongmei Zu, Shuangsuo Dang
Published online January 2, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00364
Abstract
Chronic hepatitis B (CHB) remains a significant global health challenge, and effective antiviral therapies are essential for long-term management. This study aimed to evaluate the [...] Read more.

Chronic hepatitis B (CHB) remains a significant global health challenge, and effective antiviral therapies are essential for long-term management. This study aimed to evaluate the real-world effectiveness and safety of tenofovir amibufenamide (TMF) in a cohort of patients with chronic hepatitis B (CHB).

In this multicenter, prospective, real-world cohort study, 194 CHB patients were recruited from four hospitals between August 2021 and August 2022. Patients were divided into treatment-naïve (TN, n = 123) and treatment-experienced (TE, n = 71) groups. The TN group was further subdivided into TMF (n = 63) and tenofovir disoproxil fumarate (TDF, n = 60) subgroups. In the TE group, patients transitioned from prior antiviral therapies (entecavir or TDF) to TMF after meeting criteria for poor virological response or safety concerns. Treatment response was evaluated in terms of virological effectiveness and alanine transaminase normalization rates. Virological response (VR), ALT normalization rates, renal function markers, and lipid profiles were monitored.

In the TN cohort, VR rates at 24 and 48 weeks were 42.86% and 90.48% for TMF, and 60.00% and 83.33% for TDF. ALT normalization rates at 24 and 48 weeks for TMF were 56.82% and 70.45% (according to AASLD 2018 standards). In the TE group, VR rates at 24 and 48 weeks were 83.1% and 91.55%, respectively. ALT normalization rates were 86.67% and 93.33% (local standards), and 66.67% and 76.67% (AASLD 2018 standards) (z = −2.822, P = 0.005). Additionally, TMF showed improved renal safety over TDF, with no significant differences in lipid concentrations.

TMF is comparable to TDF in terms of CHB treatment effectiveness, with better renal safety and no impact on lipid levels. In TE patients, transitioning to TMF therapy does not affect antiviral treatment outcomes.

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Review Article Open Access
Unraveling the Role of the Wnt Pathway in Hepatocellular Carcinoma: From Molecular Mechanisms to Therapeutic Implications
Zixin Liang, Shanshan Li, Zhiyu Wang, Junting Zhou, Ziyue Huang, Jiehan Li, Haolin Bao, Judy Wai Ping Yam, Yi Xu
Published online January 14, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00401
Abstract
Hepatocellular carcinoma (HCC) is one of the deadliest malignant tumors in the world, and its incidence and mortality have increased year by year. HCC research has increasingly [...] Read more.

Hepatocellular carcinoma (HCC) is one of the deadliest malignant tumors in the world, and its incidence and mortality have increased year by year. HCC research has increasingly focused on understanding its pathogenesis and developing treatments.The Wnt signaling pathway, a complex and evolutionarily conserved signal transduction system, has been extensively studied in the genesis and treatment of several malignant tumors. Recent investigations suggest that the pathogenesis of HCC may be significantly influenced by dysregulated Wnt/β-catenin signaling. This article aimed to examine the pathway that controls Wnt signaling in HCC and its mechanisms. In addition, we highlighted the role of this pathway in HCC etiology and targeted treatment.

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Review Article Open Access
Current Status and Future Perspectives on Early Detection and Diagnosis of Colorectal Cancer in China
Zhongxue Han, Qingzhou Kong, Yanqing Li
Published online December 23, 2024
Cancer Screening and Prevention. doi:10.14218/CSP.2024.00023
Abstract
Colorectal cancer (CRC) is the second most commonly diagnosed cancer in China. Early detection and diagnosis of CRC are essential for improving survival rates. However, socioeconomic [...] Read more.

Colorectal cancer (CRC) is the second most commonly diagnosed cancer in China. Early detection and diagnosis of CRC are essential for improving survival rates. However, socioeconomic factors such as regional disparities, economic conditions, and varying levels of awareness impact the uptake of screening programs. Recently, rapid advancements in non-invasive tests, including high-quality fecal immunochemical tests and the emergence of stool and blood biomarkers for CRC, have facilitated improvements in early detection and diagnosis. Additionally, image-enhanced endoscopy, a group of advanced imaging technologies, has been developed to assist in the early identification of colorectal lesions, including narrow band imaging and linked-color imaging. The emergence of artificial intelligence also offers promising opportunities to improve early diagnosis and treatment of CRC. This review mainly introduces screening technologies and the current status of CRC screening in China, provides an overview of CRC early detection and diagnosis, and discusses the limitations and future prospects.

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Review Article Open Access
Exploring the Therapeutic Potential of TGF-β Inhibitors for Liver Fibrosis: Targeting Multiple Signaling Pathways
Wanchun Zhu, Yu Cui, Jiahao Qiu, Xin Zhang, Yueqiu Gao, Zhi Shang, Lingying Huang
Published online July 15, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00029
Abstract
Liver fibrosis is a pathological process resulting from various chronic liver injuries that lead to the formation of liver fibrous scars. It can further progress to cirrhosis and [...] Read more.

Liver fibrosis is a pathological process resulting from various chronic liver injuries that lead to the formation of liver fibrous scars. It can further progress to cirrhosis and even liver cancer. Currently, there are no effective drugs specifically approved for the treatment of liver fibrosis; etiological therapy remains the main treatment strategy. Therefore, it is necessary to develop anti-fibrotic drugs targeting different pathways involved in liver fibrosis. Transforming growth factor-beta (TGF-β) is a key driver of fibrosis, and targeting TGF-β can effectively reduce liver fibrosis. In this review, we discussed the anti-liver fibrosis effects of TGF-β inhibitors through different signaling pathways, including the application of certain active ingredients from Traditional Chinese Medicine.

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Review Article Open Access
Comparative Analysis of Bioactive Ingredients and Medicinal Functions of Natural and Cultivated Ophiocordyceps sinensis (Berk.)
Zhangwen Ma, Qinghua Liu, Yongxuan Hong, Jie Chen, Jiawei Tang, Yurong Tang, Liang Wang
Published online December 23, 2024
Future Integrative Medicine. doi:10.14218/FIM.2024.00047
Abstract
The Chinese caterpillar fungus Ophiocordyceps sinensis (Berk.) is a valuable traditional medicine, also known throughout Asia by its Tibetan name དབྱར་རྩྭ་དགུན་འབུ (Yartsa Gunbu), [...] Read more.

The Chinese caterpillar fungus Ophiocordyceps sinensis (Berk.) is a valuable traditional medicine, also known throughout Asia by its Tibetan name དབྱར་རྩྭ་དགུན་འབུ (Yartsa Gunbu), meaning “summer grass, winter worm”. The mature fungus O. sinensis contains abundant active biological components, including polysaccharides, alkaloids, amino acids, inorganic elements, and others. Studies have previously confirmed that O. sinensis possesses multiple pharmacological activities. Therefore, it holds high value in the commercial market and is in increasing demand. However, the unique formation process and harsh growth environment contribute to the preciousness and scarcity of the species. To meet market demand, multiple mycelium types have been isolated from natural O. sinensis and cultivated artificially using fermentation technology. Currently, both natural and cultivated O. sinensis products are available as healthy Chinese herbal medicines on the market. However, there is a lack of comparative reviews on the two types of O. sinensis in terms of their compositions and medicinal functions. This mini-review will focus on the bioactive ingredients and medicinal functions of both natural and cultivated O. sinensis, intending to elucidate their medical values as traditional Chinese medicines for human use.

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