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Study Protocol Open Access
A Real-world Study Protocol for Treating COVID-19 Convalescent Patients with Traditional Chinese Medicine Based on Syndrome Differentiation
Qingping Deng, Zilian Ye, Xiaotu Xi, Xing Zeng, Qing Liu, Rongyuan Yang
Published online October 23, 2025
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2025.00003
Abstract
COVID-19 has resulted in significant long-term sequelae in convalescent patients, impacting overall quality of life. Traditional Chinese medicine (TCM) has shown promise in managing [...] Read more.

COVID-19 has resulted in significant long-term sequelae in convalescent patients, impacting overall quality of life. Traditional Chinese medicine (TCM) has shown promise in managing post-COVID-19 symptoms through syndrome differentiation. This study aimed to evaluate the efficacy and safety of TCM in COVID-19 convalescent patients in a real-world setting.

This prospective, real-world study will be conducted at Guangdong Provincial Hospital of Traditional Chinese Medicine. A total of 528 COVID-19 convalescent patients will be recruited and divided into two groups: a control group receiving routine Western medical treatment and an intervention group receiving additional TCM treatment based on syndrome differentiation. Patients will be assessed for three major TCM syndromes: Lung-Spleen Qi Deficiency, Qi-Yin Deficiency, and Cold Phlegm Obstructing the Lung, with corresponding TCM prescriptions administered accordingly. The primary outcome measure will be the improvement in clinical symptom scores based on a TCM symptom scoring system. Secondary outcomes will include changes in laboratory tests, imaging studies, heart function classification, and quality of life scores. Safety will be assessed through liver and kidney function tests and adverse event monitoring.

The study is expected to demonstrate that TCM treatment, based on syndrome differentiation, can significantly improve clinical symptoms and overall health in COVID-19 convalescent patients compared to routine Western medical treatment. These findings will provide evidence for integrating TCM into post-acute COVID-19 care.

This study will contribute to the evidence supporting TCM as an effective treatment for post-COVID-19 syndrome, enhancing patient outcomes and informing comprehensive recovery strategies.

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Review Article Open Access
Nutrient-stimulated Hormone-based Therapies: A New Frontier in the Prevention and Management of MASH-associated Hepatocellular Carcinoma
Richard Phillips, Yuk Ting Ma, Wasim Hanif, Tahir Shah, Shivan Sivakumar
Published online October 22, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00303
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the most common chronic liver disease in the Western world, driven by obesity, insulin resistance, and systemic [...] Read more.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the most common chronic liver disease in the Western world, driven by obesity, insulin resistance, and systemic inflammation. Its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), can culminate in cirrhosis and hepatocellular carcinoma (HCC). While lifestyle modification remains central to MASLD management, there is growing interest in pharmacological interventions, particularly nutrient-stimulated hormone-based therapies (NuSHs), such as GLP-1 receptor agonists. NuSHs exert metabolic and anti-inflammatory effects primarily via weight loss and improved insulin sensitivity. Emerging clinical data support their efficacy in resolving MASH without worsening fibrosis. However, benefits in cirrhotic patients are less evident, suggesting greater utility in early intervention. Observational studies and clinical trials suggest a reduction in liver-related morbidity with GLP-1 receptor agonist use, though fibrosis regression remains inconsistent. Preclinical models indicate that NuSHs may also reduce MASH-related HCC incidence and tumor burden, likely through systemic metabolic improvements rather than direct antineoplastic action. Observational human data following bariatric surgery reinforce this link, suggesting that weight loss itself plays a key preventive role. Herein, we propose that NuSHs are promising candidates for MASH-related HCC prevention. We provide mechanistic suggestions for how this may occur. Furthermore, incorporating NuSHs into the post-locoregional treatment pathway for HCC may delay the need for systemic anti-cancer therapies, improve immunotherapy synergy and transplant eligibility, and even slow disease progression through reversal of carcinogenic drivers. Future studies are needed to target oncological endpoints and clarify immunometabolic mechanisms to guide the integration of NuSHs into MASLD treatment algorithms.

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Original Article Open Access
DysUFMylation of SREBP1 Promotes the Progression of Hepatocellular Carcinoma by Reprogramming Lipid Metabolism
Xukang Gao, Zeping Han, Min Xu, Zhutao Wang, Guoqiang Sun, Hao Xiao, Dai Zhang, Shuangjian Qiu, Ning Ren, Chenhao Zhou, Yong Yi
Published online October 22, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00318
Abstract
Sterol regulatory element-binding protein 1 (SREBP1), a key regulator of lipogenesis, is highly expressed in tumors, but the mechanisms sustaining its elevated levels remain unclear. [...] Read more.

Sterol regulatory element-binding protein 1 (SREBP1), a key regulator of lipogenesis, is highly expressed in tumors, but the mechanisms sustaining its elevated levels remain unclear. The role of UFMylation, a posttranslational modification, in modulating SREBP1 stability and tumor progression has not been explored. This study aimed to investigate the role of UFMylation in the progression of liver cancer.

Liquid chromatography-tandem mass spectrometry was employed to investigate the interacting proteins of ubiquitin-fold modifier 1-specific ligase 1 (UFL1). Knockdown of UFL1 and DDRGK domain-containing protein 1 (DDRGK1) was performed to assess SREBP1 stability. In vitro and in vivo models of hepatocellular carcinoma (HCC) were used to evaluate tumor progression. Clinical correlations between UFL1/DDRGK1 and SREBP1 levels were analyzed in HCC patient samples.

SREBP1 undergoes UFMylation, which synergizes with ubiquitination to reduce its stability. Depletion of UFL1 or DDRGK1 increased SREBP1 stability, driving HCC progression. Clinically, UFL1 and DDRGK1 levels were reduced in HCC tissues and inversely correlated with SREBP1 expression. Fatostatin (an SREBP1 inhibitor) enhanced the therapeutic effect of Lenvatinib in HCC models with low UFL1 expression.

UFMylation is a critical posttranslational modification that destabilizes SREBP1, and its dysregulation contributes to HCC progression. Targeting the UFMylation-SREBP1 axis, particularly through Fatostatin and Lenvatinib combination therapy, represents a novel therapeutic strategy for HCC.

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Short Communication Open Access
Reporting Quality of Trend Analyses Published in Leading Medicine and Oncology Journals during 2008-2018
Xiaoling Yuan, Fei Deng, Yating Wang, Lanjing Zhang
Published online October 21, 2025
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2025.00039
Abstract
Reporting quality in clinical research is critical for evidence-based medicine and reproducibility of clinical studies. Previous work has mostly focused on the reporting quality [...] Read more.

Reporting quality in clinical research is critical for evidence-based medicine and reproducibility of clinical studies. Previous work has mostly focused on the reporting quality of clinical trials and observational longitudinal studies. However, few studies have examined the reporting quality of trend analyses. Moreover, the reporting of recommended statistical metrics in trend analyses remains largely unclear. Therefore, we assessed the reporting quality of trend analyses based on reporting of recommended statistical metrics. We systematically searched the PubMed for the trend-analysis articles published in 10 leading medicine and oncology journals over an 11-year period (2008–2018). Studies published after 2019 were excluded due to a sudden, significant increase in publication numbers during and immediately after the COVID-19 pandemic. Only original articles, research letters, and meta-analyses/systematic reviews were included. We scored the reporting quality of these articles based on whether they reported p-values, effect sizes, beta/coefficient/slope/annual-percentage-change (APC). 297 articles met the inclusion criteria. Among these, 193 (66.0%) reported p-values and 216 (72.7%) reported effect sizes. Only 13 (5.8%) analyses reported neither p-values/effect sizes nor beta/coefficient/slope/APC. In multivariable regression models, authors affiliated with epidemiology departments were less likely to report effect sizes, whereas those from statistics departments were more likely to do so. Interestingly, U.S.-based senior authors (versus non-U.S.) more likely reported p-values. No factors were independently associated with reporting APC. Overall, the reporting quality of trend analyses in leading medicine and oncology journals appears moderate and warrants improvement. We thus call for increased awareness and further research on reporting quality in trend analyses in oncology research and beyond.

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Original Article Open Access
Inflammation and Mitochondrial Dysfunction in Cirrhotic Cardiomyopathy: Therapeutic Implications
Yijie Ding, Chengfeng Huang, Guannan Yang, En Liu, Zhongxin Wang, Yong Su, Chaoliang Ge
Published online October 20, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00237
Abstract
Cirrhotic cardiomyopathy (CCM) is a significant complication of cirrhosis, but its progression and underlying mechanisms remain incompletely understood. This study aimed to investigate [...] Read more.

Cirrhotic cardiomyopathy (CCM) is a significant complication of cirrhosis, but its progression and underlying mechanisms remain incompletely understood. This study aimed to investigate dynamic changes in cardiac function, pathology, inflammation, and mitochondrial damage in a mouse model of CCM, and to compare echocardiographic characteristics in patients with cirrhosis.

Bile duct ligation was performed in male C57BL/6J mice to induce cirrhosis. Longitudinal analyses were conducted over eight weeks. Cardiac function was assessed using serum biomarkers, echocardiography, and electrocardiography. Pathology was examined with hematoxylin and eosin, Masson’s trichrome, Sirius Red, and wheat germ agglutinin staining. Western blotting and immunohistochemistry were used to detect markers of inflammation, fibrosis, apoptosis, and mitochondrial function. Cardiac and liver function markers were also evaluated in patients with cirrhosis.

Mice subjected to bile duct ligation developed progressive cardiac dysfunction, including reduced cardiac output and diastolic dysfunction (end-diastolic interventricular septal thickness, left ventricular internal diameters, stroke volume, and left ventricular end-diastolic volume decreased, whereas ejection fraction and fractional shortening increased), as well as cardiac atrophy. Myocardial apoptosis, inflammation (elevated tumor necrosis factor, interleukin-6, and p65), and fibrosis worsened over time. Mitochondrial injury was characterized by reduced carnitine palmitoyltransferase 1A and peroxisome proliferator-activated receptor alpha, with increased hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A. In patients with cirrhosis, impaired cardiac function and elevated brain natriuretic peptide levels correlated with total bilirubin.

The progression of CCM is closely associated with cirrhosis severity and appears to be driven by myocardial atrophy, apoptosis, inflammation, fibrosis, and mitochondrial dysfunction.

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Research Letter Open Access
Screening for Mutations Causing ACOX2 Deficiency-associated Hypertransaminasemia in Patients with Cryptogenic Liver Injury
Elisa Herraez, Maria J. Monte, Marta Alonso-Peña, Jesus Prieto, Luis Bujanda, Milagros Muñoz-Chimeno, Ana Avellon, Jose J.G. Marin
Published online October 17, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00329
Review Article Open Access
Unlocking the Hidden Contagions: A Deep Dive into the History, Transmission, and Prevention of Laboratory-acquired Infections
Moiz Ahmed Khan, Nida Jawaid, Sana Munir
Published online October 17, 2025
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2025.00003
Abstract
Laboratory-acquired infections (LAIs) have been documented since the first report of typhoid fever in 1885 and continue to endanger laboratory professionals despite decades of biosafety [...] Read more.

Laboratory-acquired infections (LAIs) have been documented since the first report of typhoid fever in 1885 and continue to endanger laboratory professionals despite decades of biosafety advances. This review provides a comprehensive overview of LAIs, emphasizing their history, modes of transmission, and strategies for prevention.

A systematic review of historical records, case series, and biosafety guidance (1885–2025) identified documented LAIs, their transmission routes, and preventive measures. Data were extracted on pathogen spectrum, geographic distribution, incident outcomes, and the effectiveness of biosafety interventions.

Historical analysis identified 50 laboratory-acquired typhoid infections with six deaths from 1885 to 1915, largely due to mouth pipetting and aerosol exposure. A sharp decline in fatal bacterial infections was observed following the introduction of Class II biosafety cabinets in the 1960s. From 2000 to 2021, 309 LAIs were reported across 94 studies, most commonly Salmonella enterica (56.6%), vaccinia virus (4.2%), and Brucella species (3.9%), with Brucella responsible for over half of hospital-laboratory cases (60 per 100,000 personnel-years). In Canada during 2023, 63 exposure events occurred, including three confirmed infections despite adherence to biosafety level protocols. Environmental persistence studies underscored surface-borne risks. The most effective preventative measures included abolishing mouth pipetting, mandatory use of gloves and eye/face protection, routine Class II biosafety cabinet use for aerosol-generating procedures, surface disinfection with 0.5% sodium hypochlorite, and annual competency-based biosafety training with incident reporting.

LAIs remain geographically widespread and pathogen-diverse. Quantitative historical trends and contemporary surveillance highlight critical transmission routes, including ingestion, inoculation, mucosal splash, and inhalation, while reinforcing evidence-based prevention strategies. Sustained investment in biosafety infrastructure, real-time exposure reporting, and pathogen-specific training is essential to further reduce LAI incidence and severity in the face of emerging antimicrobial resistance and novel agents.

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Review Article Open Access
Hematological and Biochemical Serum Markers in Breast Cancer: Diagnostic, Therapeutic, and Prognostic Significance
Yanjusha Madhu, Smriti Jain, Priyanka Jain, Nikita Kashyap, Kailash C. Mangalhara, Buddhi Prakash Jain
Published online October 16, 2025
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2025.00022
Abstract
Breast cancer remains one of the most common cancers affecting women globally, with late detection frequently contributing to its high mortality rate. Multiple factors drive these [...] Read more.

Breast cancer remains one of the most common cancers affecting women globally, with late detection frequently contributing to its high mortality rate. Multiple factors drive these delays, including a lack of awareness, financial constraints in low-income countries, and limited access to non-invasive and accurate biomarkers. This review aims to introduce biomarkers, particularly hematological and biochemical serum markers, as essential, non-invasive, and accurate tools for improving the diagnosis, prognosis, and therapeutic management of breast cancer. Hematological markers are measurable blood parameters that reflect physiological and pathological processes such as inflammation, infection, cardiovascular stress, autoimmune conditions, and cancer. Routinely measured hematological markers, such as the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and red blood cell indices, are typically obtained from standard tests like the complete blood count. Regular monitoring through complete blood count is essential during cancer treatment to evaluate changes in blood cell counts and detect potential adverse effects. Because of their affordability, minimal infrastructure requirements, and broad accessibility, hematological parameters have been increasingly studied for their association with high-risk factors in breast cancer, particularly in resource-limited settings. Their utility underscores their critical role in improving patient outcomes across diverse healthcare environments. This review summarizes the clinical value of various hematological and serum-based biochemical markers in the screening and diagnosis of breast cancer. Prediction methods that incorporate hematological and serum-based biochemical parameters can support screening, diagnosis, and staging. Overall, individual or combined blood indicators hold significant potential to enhance diagnostic accuracy and effectiveness.

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Research Letter Open Access
Original Article Open Access
Gene–environment Interaction of GWAS Loci and Reproductive History in Uterine Fibroid Risk: A Case-control Study
Liubov Ponomareva, Ekaterina Barysheva, Anna Dorofeeva, Ksenia Kobzeva, Olga Bushueva
Published online October 14, 2025
Gene Expression. doi:10.14218/GE.2025.00056
Abstract
Uterine fibroids (UFs) are common hormone-dependent tumors with a complex etiology involving both genetic and environmental factors. This study aimed to investigate, for the first [...] Read more.

Uterine fibroids (UFs) are common hormone-dependent tumors with a complex etiology involving both genetic and environmental factors. This study aimed to investigate, for the first time, the associations between loci from genome-wide association studies (GWAS) and environmental risk factors in UF development, with a particular focus on gene–environment interactions.

DNA samples from 737 women with UF and 451 healthy controls were genotyped for ten UF-associated GWAS single nucleotide polymorphisms (SNPs) using probe-based polymerase chain reaction in this case-control study.

SNP rs66998222 (LOC102723323, G/A) was associated with decreased UF risk in the total sample (odds ratio (OR) = 0.81, p = 0.038) and in patients with a history of induced abortion (OR = 0.70, p = 0.009). SNP rs11031731 (THEM7P, WT1, G/A) increased UF risk overall (OR = 1.39, p = 0.01), and in women with abortion history (OR = 1.60, p = 0.008) or without pelvic inflammatory disease (OR = 1.43, p = 0.02). SNPs rs641760 (PITPNM2, C/T) and rs2553772 (LOC105376626, G/T) showed protective effects depending on abortion history. SNP rs1986649 (FOXO1, C/T) was associated with later UF onset (p = 0.049) and slower growth (p = 0.017). GWAS loci influence UF-related genes involved in proliferation, inflammation, and hormone metabolism, underscoring their pathogenic role.

Induced abortions and inflammation modify the effects of GWAS-identified UF risk loci, with allele-specific impacts on hormonal, inflammatory, and repair pathways. Replication in diverse cohorts is needed to validate these population-specific effects.

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