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Review Article Open Access
Unraveling the Oncogenic Potential of microRNAs in Lung Cancer: A Narrative Review Article
Ali Moradi, Mohammad Bayat, Parvin Pourmasoumi, Sufan Chien
Published online March 19, 2025
Cancer Screening and Prevention. doi:10.14218/CSP.2025.00001
Abstract
Lung cancer (LC) remains the leading cause of cancer-related deaths worldwide, characterized by high mortality rates and limited treatment options. MicroRNAs (miRNAs) are critical [...] Read more.

Lung cancer (LC) remains the leading cause of cancer-related deaths worldwide, characterized by high mortality rates and limited treatment options. MicroRNAs (miRNAs) are critical regulators of gene expression and play significant roles in the development of LC. This review aimed to provide a comprehensive analysis of oncogenic miRNAs involved in LC, focusing on their dysregulation, functional roles, and potential implications for diagnosis and therapy. In this review, we collected data from published literature, specifically selecting English articles closely related to the topic. We conducted a thorough review of studies published between 2013 and 2023, utilizing prominent academic databases such as PubMed, Scopus, and Google Scholar to gather relevant data. Our investigation highlights several oncogenic miRNAs that have been shown to play critical roles in lung cancer biology, including miR-9-5p, miR-21, and miR-31. These miRNAs are known to facilitate various key processes, such as tumor cell proliferation, enhanced migratory capabilities, and the development of resistance to chemotherapeutic agents. Additionally, miRNAs present significant diagnostic and therapeutic potential. In conclusion, the unique roles and regulatory networks of miRNAs in LC warrant extensive further research. Further research is essential to uncover the complex networks of miRNAs and to develop innovative miRNA-based therapies for lung cancer.

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Review Article Open Access
Molecular and Histological Profiles and Relevant Imaging Signatures of Intrahepatic Cholangiocarcinoma
Huizhen Huang, Feng Chen
Published online April 30, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00410
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is the second most prevalent primary liver cancer, characterized by insidious onset and high malignancy. Many patients are diagnosed at an [...] Read more.

Intrahepatic cholangiocarcinoma (iCCA) is the second most prevalent primary liver cancer, characterized by insidious onset and high malignancy. Many patients are diagnosed at an inoperable stage, and the effectiveness of chemotherapy and radiotherapy remains limited. This study aimed to provide a comprehensive review of the histological classification, genetic alterations, molecular subtypes, and corresponding imaging signatures of iCCA, highlighting its heterogeneity and offering insights into targeted therapy and personalized treatment. The heterogeneity of iCCA poses significant challenges to both targeted therapy and immunotherapy, necessitating in-depth exploration at the molecular and subtyping levels. Investigating genetic variations, signaling pathway alterations, and molecular subtypes can aid in patient stratification. Stratifying iCCA patients allows for more precise treatment selection, ultimately improving survival outcomes. Imaging, as a non-invasive tool, holds substantial potential for predicting subtypes and molecular profiles. It is possible to infer histological and molecular features from imaging, or to interpret imaging signatures in light of known histological and molecular data. This integrative approach, combining external imaging with internal molecular insights, fosters a comprehensive understanding of iCCA’s characteristics and enhances clinical management.

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Original Article Open Access
Plasma Extracellular Vesicle-derived MicroRNA Associated with Human Alpha-1 Antitrypsin Deficiency-mediated Liver Disease
Regina Oshins, Zhiguang Huo, Zachary Greenberg, Virginia Clark, Sergio Duarte, Huiping Zhou, Jesse West, Mei He, Mark Brantly, Nazli Khodayari
Published online November 19, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00253
Abstract
Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder associated with liver disease, ranging from fibrosis to hepatocellular carcinoma. The disease remains asymptomatic until [...] Read more.

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder associated with liver disease, ranging from fibrosis to hepatocellular carcinoma. The disease remains asymptomatic until its final stages when liver transplantation is the only available therapy. Biomarkers offer an advantage for disease evaluation. The presence of microRNAs (miRNAs) in plasma extracellular vesicles (EVs) presents a noninvasive approach to assess the molecular signatures of the disease. In this study, we aimed to identify miRNA biomarkers to distinguish molecular signatures of the liver disease associated with AATD in AATD individuals.

Using small RNA sequencing and qPCR, we examined plasma EV miRNAs in healthy controls (n = 20) and AATD patients (n = 17). We compared the EV miRNAs of AATD individuals with and without liver disease, developing an approach for detecting liver disease. A set of miRNAs identified in the AATD testing cohort was validated in a separate cohort of AATD patients (n = 45).

We identified differential expression of 178 EV miRNAs in the plasma of the AATD testing cohort compared to controls. We categorized AATD individuals into those with and without liver disease, identifying 39 differentially expressed miRNAs. Six miRNAs were selected to test their ability to discriminate liver disease in AATD. These were validated for their specificity and sensitivity in an independent cohort of 45 AATD individuals. Our logistic model established composite scores with three- and four-miRNA combinations, achieving areas under the curve of 0.737 and 0.751, respectively, for predicting AATD liver disease.

We introduce plasma EV-derived miRNAs as potential biomarkers for evaluating AATD liver disease. Plasma EV-associated miRNAs may represent a molecular signature of AATD liver disease and could serve as valuable tools for its detection and monitoring.

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Original Article Open Access
Burden of Liver Cancer Attributable to Hepatitis B and Alcohol Globally, in China, and for Five Sociodemographic Index Regions from 1990 to 2021: A Population-based Study
Xiuxiu Deng, Hui Li, Yuru Zhong, Haibo Wang, Lixin Ke, Zhifei Wang, Alexios-Fotios A. Mentis, Yangqin Xun, Qiang Zhang, Cuncun Lu
Published online November 11, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00351
Abstract
Liver cancer is a digestive system malignancy that poses a significant public health challenge globally. This study aimed to analyze and compare the epidemiological trends of liver [...] Read more.

Liver cancer is a digestive system malignancy that poses a significant public health challenge globally. This study aimed to analyze and compare the epidemiological trends of liver cancer attributed to hepatitis B (LCHB) and alcohol use (LCAL) over the past 32 years.

Data on mortality and disability-adjusted life years for LCHB and LCAL in China, globally, and across five sociodemographic index regions were obtained from the Global Burden of Disease 2021 database and comprehensively analyzed.

In 2021, the global and Chinese death counts and disability-adjusted life years attributed to LCHB and LCAL showed substantial increases compared to 1990. China had the highest number of deaths from LCHB and LCAL among 204 countries and regions. Gender and age disparities were notable, with males and those aged 40–75 years bearing a higher burden than females and other age groups. Global age-period-cohort analysis revealed an escalating risk of death from LCHB with age, alongside a lower risk in younger cohorts and more recent periods. The mortality risk for LCAL also increased with age but exhibited distinct cohort and period effects compared to LCHB. Decomposition analysis indicated that shifts in the global burden of LCHB and LCAL were influenced by population growth, with population aging playing a crucial role in China.

A significant burden of LCHB and LCAL persists, highlighting the need for tailored prevention, screening, and control strategies to mitigate their incidence, as well as the identification of advanced therapeutics to reduce mortality.

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Review Article Open Access
Lipid Metabolic Reprogramming and the Tumor Immune Microenvironment: A New Strategy for Early Diagnosis and Cancer Prevention
Xiaoshuang Liu, Lihua Ren, Ruihua Shi
Published online March 30, 2025
Cancer Screening and Prevention. doi:10.14218/CSP.2025.00002
Abstract
Reprogramming of lipid metabolism has emerged as a significant characteristic of malignancy during tumor development. Research indicates a critical link between lipid metabolism [...] Read more.

Reprogramming of lipid metabolism has emerged as a significant characteristic of malignancy during tumor development. Research indicates a critical link between lipid metabolism and the tumor immune microenvironment. This relationship not only facilitates cancer progression by remodeling the tumor microenvironment but also influences the functionality of immune cells. Alterations in lipid metabolism regulate the function and status of immune cells within the microenvironment, impacting immune evasion and the therapeutic efficacy of tumors. Consequently, targeting lipid metabolism is a viable strategy for intervening in tumorigenesis and tumor development. This review examines the roles of key lipid molecules, such as fatty acids and cholesterol, within the tumor microenvironment, highlighting how aberrant lipid metabolism can alter immune cell function. By investigating the interactions between lipid metabolism and immune cells in this setting, the review offers novel insights into early diagnosis, screening, and immunotherapy of malignant tumors. Furthermore, lipid metabolic reprogramming may act as a biomarker for monitoring early immune escape from tumors and predicting therapeutic outcomes, thereby enhancing early diagnosis and personalized cancer treatment.

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Original Article Open Access
Relationship between Concentrations of Oxygen and Levels of Oxidative Stress in Patients Receiving Oxygen Therapy for Severe COVID-19 Pneumonia
Salih Özenç, Pınar Yıldız Gülhan, Merve Alpay, Şule Yıldız, Nevra Ezgi Yaşlı, Peri Meram Arbak
Published online November 14, 2024
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00015
Abstract
Severe COVID-19 pneumonia often requires high concentrations of oxygen, which can potentially lead to oxidative stress and lung injury. This study aimed to investigate the impact [...] Read more.

Severe COVID-19 pneumonia often requires high concentrations of oxygen, which can potentially lead to oxidative stress and lung injury. This study aimed to investigate the impact of different oxygen therapy modalities on oxidative stress by comparing malondialdehyde (MDA) levels, an oxidative stress marker, and glutathione (GSH), an antioxidant marker, in patients with severe COVID-19 pneumonia.

This study included 50 patients with COVID-19 pneumonia who received oxygen therapy using a reservoir mask at ≥15 L/m, high-flow oxygen therapy at 60 L/m, or oxygen therapy with noninvasive mechanical ventilation at fraction of inspired O2 (FiO2) levels of ≥60%. GSH and MDA levels were measured 48 h after starting oxygen therapy at FiO2 ≥ 60% and 48 h after switching to nasal cannula oxygen therapy at 2–4 L/m.

Overall, 60% (n = 30) of the patients were men, and 40% (n = 20) were women. In patients with accompanying hypertension, MDA levels, which were higher during oxygen therapy at FiO2 ≥ 60%, decreased significantly after switching to nasal cannula oxygen therapy at 2–4 L/m (p = 0.046). A significant difference in MDA was not found after switching to lower oxygen flow (p = 0.064) in patients with underlying diabetes mellitus. GSH levels in patients with underlying diabetes mellitus were higher during oxygen therapy at FiO2 ≥ 60% and decreased significantly after switching to nasal cannula oxygen therapy at 2–4 L/m (p = 0.021).

This study compared MDA and GSH levels among patients receiving oxygen therapy at high and low concentrations for severe COVID-19 pneumonia. The results revealed that patients who died of COVID-19 pneumonia had significantly higher mean MDA levels than those who survived. In patients with underlying HT, MDA levels, which were higher during oxygen therapy at FiO2 ≥ 60%, decreased during nasal oxygen therapy at 2–4 L/m; this difference was significant. The increase in serum MDA levels during high-flow oxygen therapy and the decrease during low-flow therapy in patients with COVID-19 pneumonia accompanied by hypertension suggest that oxidative stress due to hyperoxia should be taken into consideration.

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Review Article Open Access
The Link Between Immune Aging and Type 2 Diabetes: A Review of Mechanisms and Implications
Swarup K. Chakrabarti, Dhrubajyoti Chattopadhyay
Published online July 1, 2025
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2025.00018
Abstract
Type 2 diabetes (T2D) is a metabolic disorder characterized by insulin resistance (IR), inflammation, and dysregulation in glucose metabolism. The disease is spreading globally, [...] Read more.

Type 2 diabetes (T2D) is a metabolic disorder characterized by insulin resistance (IR), inflammation, and dysregulation in glucose metabolism. The disease is spreading globally, partly due to aging, which can damage the immune system and speed up the progression of the metabolic disorder. This review primarily delves into the triggers for T2D within the framework of the ominous octet, which emphasizes 8 principal factors under the “ominous octet” framework that contribute to high blood glucose and associated metabolic disorders. The article studies the interplay of hyperinsulinemia, mitochondrial dysfunction (MD), and endoplasmic reticulum (ER) stress with immune aging in driving disease progression affecting each component of the octet. MD and ER stress can result in defects in insulin signaling, ultimately leading to β-cell death. Chronic inflammation associated with aging, also known as inflammaging, especially affects older adults by worsening IR and glucose regulation, which creates a continuous sequence of metabolic problems. Thus, the “ominous octet” framework provides fundamental knowledge to develop personalized treatment approaches that target metabolic dysfunction together with ER stress, MD, and immune system imbalances. These strategies show promising potential to improve treatments for T2D and may lead to better health outcomes for older adults dealing with this condition.

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Original Article Open Access
Prevalence of Hepatitis D Virus Antibody Positivity in Chinese Patients with Chronic Hepatitis B Virus Infection
Xieer Liang, Qiaoqiao Chen, Hong Tang, Yujuan Guan, Minfeng Liang, Peng Hu, Wen Xie, Huiying Rao, Junqi Niu, Liang Chen, Li Yan, Xiaowei Chen, Xiaohe Li, Yulin Zhao, Oliver Lenz, Michael Biermer, Jinlin Hou
Published online February 24, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00313
Abstract
Large-scale data on the hepatitis D virus (HDV)/hepatitis B virus (HBV) co-infection rate is needed to estimate the current epidemiology of HDV in China. This study aimed to estimate [...] Read more.

Large-scale data on the hepatitis D virus (HDV)/hepatitis B virus (HBV) co-infection rate is needed to estimate the current epidemiology of HDV in China. This study aimed to estimate the current epidemiology of HDV.

Patients with chronic HBV infection, with documented serum hepatitis B surface antigen (HBsAg) positivity for more than six months, were enrolled across China. Blood samples were collected at baseline for central evaluations of HDV antibody and HBsAg quantification. Assessments for antibodies of hepatitis A virus, hepatitis C virus, hepatitis E virus, and human immunodeficiency virus, as well as HDV RNA quantification, were performed in patients who tested positive for HDV antibodies.

Of the 5,044 enrolled patients between September 24, 2021, and December 28, 2022, 4,936 patients were included in the analysis. The mean age (±standard deviation) was 42.9 ± 9.9 years, and 69.8% of patients were male. The mean alanine aminotransferase level was 34 ± 58 U/L, and 1,509 (30.6%) patients were hepatitis B e antigen-positive. The mean (standard deviation) HBsAg level at baseline was 3,535 ± 11,292 IU/mL among 4,842 patients who were HBsAg positive. The rate of HBV infection and HDV antibody positivity was 0.24% (95% confidence interval: 0.1–0.4%), and only one patient was HDV RNA positive.

The prevalence of HDV antibody positivity was 0.24% in Chinese patients with chronic HBV infection, and only one patient with both anti-HDV antibody and HDV RNA positivity was observed in this study.

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Review Article Open Access
The Role of Novel Immunomodulators in the Treatment of Autoimmune Hepatitis
Jing Li, Huanhuan Wang, Jie Lin, Aili Wang, Shuiyin Miao, Huaie Liu
Published online May 13, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00008
Abstract
Autoimmune hepatitis (AIH) is a chronic, progressive inflammatory liver disease characterized by autoimmune-mediated hepatic injury. Currently, glucocorticoid drugs, primarily prednisone, [...] Read more.

Autoimmune hepatitis (AIH) is a chronic, progressive inflammatory liver disease characterized by autoimmune-mediated hepatic injury. Currently, glucocorticoid drugs, primarily prednisone, with or without azathioprine, are commonly recommended as first-line therapeutic agents in treatment guidelines by many scientific associations. However, the primary objective of treatment is to achieve a complete biochemical response, which is defined as the normalization of both transaminases and immunoglobulin G levels within six to twelve months. Ideally, this should also be accompanied by histological remission. Nevertheless, corticosteroid therapy is associated with significant adverse effects, potentially resulting in treatment discontinuation. In this context, it has become evident that standard treatment is inadequate for a proportion of patients, leading to the emergence of other treatment options and lines. Novel immunomodulatory agents, a class of drugs that regulate the body’s immune functions, have been confirmed to possess properties that modulate immune balance and induce immune tolerance. In recent years, these agents have played an increasingly significant role in the clinical management of AIH. This article provided an in-depth review of recent advancements in the development of novel immunomodulators, including immune cell nucleic acid inhibitors, calmodulin phosphate inhibitors, mammalian target of rapamycin inhibitors, tumor necrosis factor-α inhibitors, interleukin-2, anti-CD20 monoclonal antibodies, and B cell-activating factor inhibitors, for the treatment of AIH.

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Original Article Open Access
Association of Waist Circumference with All-cause and Cardiovascular Mortalities in Diabetes from the National Health and Nutrition Examination Survey 2003–2018
Huizhong Ji, Bin Song, Xuehui Li, Hui Chen, Xueli Sun, Tian Tian, Yang Geng, Xin Wang, Hengzhong Zhang, Yumei Wu, Yan Liu, Changjun Pei, Ling Cao
Published online December 31, 2024
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00400
Abstract
Waist circumference (WC) is closely associated with metabolic diseases, including diabetes mellitus (DM), metabolic syndrome, and mortality. However, the correlation between WC [...] Read more.

Waist circumference (WC) is closely associated with metabolic diseases, including diabetes mellitus (DM), metabolic syndrome, and mortality. However, the correlation between WC and mortality varies across populations and has rarely been examined specifically in patients with DM. In this study, we explored the relationships between WC and both all-cause and cardiovascular mortalities among individuals with DM.

Participants from the National Health and Nutrition Examination Survey 2003–2018 included 3,151 women and 3,473 men with DM who had baseline WC measurements. Survival data were collected from enrollment until December 31, 2019. Cox proportional hazard models were adjusted for demographic features and other confounders. Restricted cubic spline curves and threshold effect analyses were performed separately for men and women. Sensitivity analyses were conducted to minimize reverse causality.

Among 6,624 participants with DM, 621 women and 871 men died during median follow-ups of 6.8 and 6.3 years, respectively. WC demonstrated a U-shaped association with all-cause and cardiovascular mortalities in women, and a J-shaped trend in men. The optimal WC thresholds for minimizing mortality risk were 107.0 cm for women and 89.0 cm for men. For women, adjusted hazard ratios for all-cause mortality were 0.97 (95% confidence interval (CI): 0.96–0.98, P < 0.001) for WC below 107.0 cm and 1.04 (95% CI: 1.02–1.05, P < 0.001) for WC above 107.0 cm. In men, the corresponding ratios were 0.94 (95% CI: 0.90–0.97, P < 0.001) for WC below 89.0 cm and 1.03 (95% CI: 1.02–1.05, P < 0.001) for WC above 89.0 cm.

WC showed a U-shaped association with all-cause and cardiovascular mortalities in women and a J-shaped association in men among U.S. adults with DM from the National Health and Nutrition Examination Survey. Further research is needed to explore the underlying mechanisms rather than promoting preconceived notions about an optimal WC.

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