Review Article
Open Access
An Overview of Advancements in Screening Methods and Point-of-care Diagnostics for Colorectal Cancer
Pankaj Kumar, Zahid Bashir Zargar, Rohini Sharma, Sunil Kumar, Kanwaljit Chopra, Sandip V. Pawar
Published online May 28, 2025
Cancer Screening and Prevention.
doi:10.14218/CSP.2025.00006
Abstract
Colorectal cancer (CRC) is a type of cancer that originates in the colon or rectum from precancerous polyps, which can evolve into cancerous growths over time. This review aimed
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Colorectal cancer (CRC) is a type of cancer that originates in the colon or rectum from precancerous polyps, which can evolve into cancerous growths over time. This review aimed to provide a comprehensive analysis of CRC, its subtypes, clinical manifestations, point-of-care diagnostic approaches, and management strategies. The clinical presentation of CRC often includes symptoms such as blood in stool, changes in bowel habits, abdominal discomfort, weight loss, fatigue, a feeling of incomplete bowel emptying, and anemia. The identification of these signs prompts healthcare professionals to initiate diagnostic measures without delay. Point-of-care diagnosis plays a pivotal role in the early detection of CRC, employing screening tests such as stool tests and colonoscopies. These diagnostic modalities enable healthcare professionals to identify precancerous polyps or early-stage tumors, facilitating timely intervention and significantly improving treatment outcomes. Adherence to screening guidelines is crucial for the prevention and early detection of CRC. Despite advancements in screening and treatment options, there remains a crucial need for more specific, minimally invasive screening methods with minimal side effects. By improving current detection methods, a better screening approach for CRC can be developed. Recent advancements, including single-cell sequencing, spatial transcriptomics, and artificial intelligence integration, hold great promise for enhancing early diagnosis and advancing personalized treatment strategies. Moreover, a healthy lifestyle, including a balanced diet, regular exercise, no tobacco use, and limited alcohol consumption, can significantly lower the risk of CRC. By emphasizing the importance of lifestyle modifications, early screening, and timely intervention, healthcare professionals can significantly reduce the burden of CRC and improve patient outcomes.
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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
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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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Open Access
Association between TLR10 rs10004195 Gene Polymorphism and Risk of Helicobacter pylori Infection: A Meta-analysis
Zijie Xu, Wei Li, Wenli Li, Dalei Jiang, Quanjiang Dong, Lili Wang
Published online October 17, 2024
Exploratory Research and Hypothesis in Medicine.
doi:10.14218/ERHM.2024.00023
Abstract
Helicobacter pylori (H. pylori) infection can cause multiple secondary digestive disorders. Some studies have found that polymorphisms in Toll-like receptor (TLR) genes, including
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Helicobacter pylori (H. pylori) infection can cause multiple secondary digestive disorders. Some studies have found that polymorphisms in Toll-like receptor (TLR) genes, including TLR10 rs10004195, may be associated with increased susceptibility to H. pylori infection. Despite conflicting reports, we conducted a meta-analysis to clarify the relationship between these factors.
We conducted an exhaustive review, encompassing all relevant literature up to February 2024, using databases such as PubMed, Embase, Web of Science, and the China National Knowledge Infrastructure. We screened studies based on specific criteria and evaluated their quality using the Newcastle-Ottawa scale. Heterogeneity testing and meta-analysis were performed using Stata 17.0 software, and SPSSAU was used for publication bias evaluation and sensitivity analysis.
Eight of the 487 identified studies met the inclusion criteria, comprising 3,004 and 2,140 individuals in the H. pylori-positive and negative control groups, respectively. Our results demonstrated that individuals carrying the AA genotype at the TLR10 rs10004195 locus had a significantly increased likelihood of H. pylori infection when analyzed using the recessive genetic model (OR: 1.64, CI: 1.04–2.58, p = 0.034). No statistically significant associations were found in the other four genetic models.
Our findings suggest that carrying the TLR10 rs10004195 AA genotype is associated with a significantly elevated risk of H. pylori infection. This information could be used to assess future risk of H. pylori infection in healthy individuals and provide personalized health guidance based on individual genetic polymorphisms.
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Open Access
Hydronidone for the Treatment of Liver Fibrosis Associated with Chronic Hepatitis B: Protocol for a Phase 3 Randomized Trial
Xiaobo Cai, Yin Qu, Wen Xie, Yanbin Wang, Mengyu Zhao, Ling Zhang, Ying Luo, Ping Yin, Jun Cheng, Lungen Lu
Published online March 10, 2025
Journal of Clinical and Translational Hepatology.
doi:10.14218/JCTH.2024.00472
Abstract
Liver fibrosis is a key process in the progression of chronic liver diseases. However, there are currently no drugs specifically designed to treat liver fibrosis. Our Phase 2 trial
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Liver fibrosis is a key process in the progression of chronic liver diseases. However, there are currently no drugs specifically designed to treat liver fibrosis. Our Phase 2 trial of hydronidone for the treatment of chronic hepatitis B (CHB)-associated liver fibrosis showed that adding hydronidone to entecavir resulted in significant reversal of liver fibrosis. To further evaluate the efficacy of a 270 mg/day dose of hydronidone for treating liver fibrosis associated with CHB, we conducted this Phase 3 trial.
This is a 52-week, randomized (1:1), double-blind, placebo-controlled, multicenter, entecavir-based Phase 3 clinical study conducted at 44 study centers across China. Adult patients aged 18 to 65 years with significant liver fibrosis (defined as an Ishak score ≥ 3 on liver biopsy) associated with CHB were included.
The primary endpoint of the trial is to demonstrate the efficacy of fibrosis reversal, defined as a decrease in the Ishak stage score of liver fibrosis by ≥1 after 52 weeks of treatment, compared to baseline.
The results of this trial are expected to further support the antifibrotic indication for this novel drug.
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Original Article
Open Access
Biomarker Discovery for Metabolic Dysfunction-associated Steatotic Liver Disease Utilizing Mendelian Randomization, Machine Learning, and External Validation
Gong Feng, Giovanni Targher, Christopher D. Byrne, Na He, Man Mi, Yi Liu, Hongbin Zhu, Ming-Hua Zheng, Feng Ye
Published online July 16, 2025
Journal of Clinical and Translational Hepatology.
doi:10.14218/JCTH.2025.00270
Abstract
The causal biomarkers for metabolic dysfunction-associated steatotic liver disease (MASLD) and their clinical value remain unclear. In this study, we aimed to identify biomarkers
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The causal biomarkers for metabolic dysfunction-associated steatotic liver disease (MASLD) and their clinical value remain unclear. In this study, we aimed to identify biomarkers for MASLD and evaluate their diagnostic and prognostic significance.
We conducted a Mendelian randomization analysis to assess the causal effects of 2,925 molecular biomarkers (from proteomics data) and 35 clinical biomarkers on MASLD. Mediation analysis was performed to determine whether clinical biomarkers mediated the effects of molecular biomarkers. The association between key clinical biomarkers and MASLD was externally validated in a hospital-based cohort (n = 415). A machine learning–based diagnostic model for MASLD was developed and validated using the identified molecular biomarkers. Prognostic significance was evaluated for both molecular and clinical biomarkers.
Six molecular biomarkers—including canopy FGF signaling regulator 4 (CNPY4), ectonucleoside triphosphate diphosphohydrolase 6 (ENTPD6), and major histocompatibility complex, class I, A (HLA-A)—and eight clinical biomarkers (e.g., serum total protein (STP)) were identified as causally related to MASLD. STP partially mediated the effect of HLA-A on MASLD (23.61%) and was associated with MASLD in the external cohort (odds ratio = 1.080, 95% confidence interval: 1.011–1.155). A random forest model demonstrated high diagnostic performance (AUC = 0.941 in training; 0.875 in validation). High expression levels of CNPY4 and ENTPD6 were associated with the development of and poorer survival from hepatocellular carcinoma. Low STP (<60 g/L) predicted all-cause mortality (HR = 2.50, 95% confidence interval: 1.22–5.09).
This study identifies six causal molecular biomarkers (e.g., CNPY4, ENTPD6, HLA-A) and eight clinical biomarkers for MASLD. Notably, STP mediates the effect of HLA-A on MASLD and is associated with all-cause mortality.
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Original Article
Open Access
Floating Nanoballoons for Improved Bioavailability and Sustained Release Anti-inflammatory Effect of Ibuprofen
Anil K. Philip, Betty Annie Samuel, Bassim A Mohammed, Hayder A Al-Aubaidy
Published online December 25, 2024
Journal of Exploratory Research in Pharmacology.
doi:10.14218/JERP.2024.00027
Abstract
Poor bioavailability and a short half-life limit the therapeutic efficacy of ibuprofen. This study developed floating nanoballoons to enhance ibuprofen’s bioavailability and sustain
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Poor bioavailability and a short half-life limit the therapeutic efficacy of ibuprofen. This study developed floating nanoballoons to enhance ibuprofen’s bioavailability and sustain its anti-inflammatory effects through improved gastric retention.
Ibuprofen-loaded nanoballoons were synthesized using solvent evaporation with ethyl cellulose as the polymer matrix. The formulation was characterized for morphology, buoyancy, drug loading, and release kinetics. In vivo studies assessed the anti-inflammatory efficacy in acute and chronic inflammation models using male Sprague-Dawley rats.
The nanoballoons exhibited optimal characteristics, including 96% buoyancy and a drug loading efficiency of 96.54 ± 1.32%. Scanning Electron Microscopy revealed a spherical morphology with a porous structure. Drug release followed a biphasic pattern: an initial release of 35.23 ± 2.13% over 2 h, followed by sustained release reaching 97.54 ± 1.30% at 12 h. In acute inflammation studies, the nanoballoon formulation showed superior edema inhibition (68.12%) compared to pure ibuprofen (51.67%). Chronic inflammation studies demonstrated significant improvements in inflammatory markers: reduced TNF-α (19.12 ± 0.48 vs. 31.11 ± 1.23 pg/mL), hs-CRP (201.7 ± 11.02 vs. 232.12 ± 11.33 ng/mL), and IL-6 (100.01 ± 18.40 vs. 135 ± 11.22 pg/mL), with increased anti-inflammatory IL-10 (507.18 ± 10.11 vs. 276.11 ± 19.16 pg/mL).
The developed floating nanoballoon system significantly enhanced ibuprofen’s bioavailability and anti-inflammatory efficacy, presenting a promising gastro-retentive delivery platform for poorly water-soluble drugs.
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Review Article
Open Access
Foundation and Practice of Digital Traditional Chinese Medicine Platforms in Enhanced Recovery After Surgery
Xiaochun Zhang, Guanwen Gong, Zhiwei Jiang, Heiying Jin
Published online March 25, 2025
Future Integrative Medicine.
doi:10.14218/FIM.2025.00011
Abstract
This review explores the integration of complexity science—specifically, the biological holographic phenomenon and chaos-fractal theory—with the fundamental principles of traditional
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This review explores the integration of complexity science—specifically, the biological holographic phenomenon and chaos-fractal theory—with the fundamental principles of traditional Chinese medicine (TCM) to optimize perioperative recovery. It examines how these theories provide a scientific foundation for developing a digital TCM diagnosis and treatment platform. Key topics discussed include the application of digital four-diagnosis technology, visualization of perioperative Yin-Yang states, and artificial intelligence-driven biomarker discovery. By quantifying and digitizing core TCM concepts, this approach enables their incorporation into Enhanced Recovery After Surgery protocols. Ultimately, the review highlights the potential of integrating TCM with Western medicine to advance personalized postoperative management, offering both theoretical insights and practical strategies for improving perioperative care.
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Original Article
Open Access
Improved Discrimination and Predictive Ability of Novel Prognostic Scores for Long-term Mortality in Hospitalized Patients with Cirrhosis
Sipu Wang, Gaoyue Guo, Han Wang, Xuqian Zhang, Wanting Yang, Jie Yang, Liping Wu, Chao Sun
Published online March 11, 2025
Journal of Clinical and Translational Hepatology.
doi:10.14218/JCTH.2025.00004
Abstract
Since the adoption of novel prognostic scores, such as the iterative model for end-stage liver disease (MELD 3.0) and the gender-equity model for liver allocation (GEMA), their
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Since the adoption of novel prognostic scores, such as the iterative model for end-stage liver disease (MELD 3.0) and the gender-equity model for liver allocation (GEMA), their utility has markedly expanded to diverse clinical scenarios. However, data concerning their prognostic value in more generalized cirrhotic populations are scarce. In this study, we aimed to elucidate the MELD 3.0/GEMA-Na for long-term mortality risk stratification and refine their usage scope.
This study retrospectively reviewed 310 hospitalized patients with decompensated cirrhosis. Discrimination and stratification were compared between MELD 3.0/GEMA-Na and other scores. Validation was performed in another 120 subjects.
In the investigated cohort, the median MELD-Na, MELD 3.0, and GEMA-Na were 9 (7, 12), 12 (10, 17), and 12 (9, 17), respectively. Compared to their predecessors, both MELD 3.0 and GEMA-Na models exhibited consistently better discriminative ability, especially in relation to long-term mortality. This effect was more pronounced for GEMA-Na, which was the only score to present an area under the receiver operating characteristic curve greater than 0.8 up to two years (0.807). Statistical analysis indicated that a MELD 3.0 score of 18 and a GEMA-Na score of 20 were the most optimal cutoffs to rank the risk of death, both of which were independently associated with two-year all-cause transplant-free mortality (MELD 3.0: hazard ratio: 1.13, 95% confidence interval: 1.10, 1.17; GEMA-Na: hazard ratio: 1.12, 95% confidence interval: 1.10, 1.17, both P < 0.001). Similar findings were affirmed in the validation cohort.
MELD 3.0 is superior to other MELD-based scores for long-term prognostication in hospitalized patients with cirrhosis, while GEMA-Na demonstrated even better accuracy and performance.
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Original Article
Open Access
Clinical, Microbiological, and Antibiotic Treatment Characteristics of Bacterial Infections in Patients with Liver Cirrhosis in China: A Multicenter Study
Xiuding Zhang, Haoda Weng, Qinzhi Deng, Min Deng, Xuwei Wu, Zuxiong Huang, Shourong Liu, Rui Wu, Chunlian Ma, Yao Xu, Jianfeng Zhong, Jie Yang, Yinxia Wu, Huajiang Shen, Feng Ding, Fang Wang, Xuezhen Zhai, Chunxian Peng, Haotang Ren, Jie Jin, Xiangfei Xu, Xiaofei Li, Xiaoting Ye, Guoqing Qian, Shuilin Sun, Xuebing Yao, Haifeng Miao, Qianggu Xiao, Shaoheng Ye, Qing Zhang, Xinyi Xu, Xia Yu, Yue Yu, Yan Lan, Huilan Tu, Xianbin Xu, Xinrong Zhang, Rui Huang, Xiaohan Qian, Qiao Yang, Jifang Sheng, Yu Shi
Published online July 3, 2025
Journal of Clinical and Translational Hepatology.
doi:10.14218/JCTH.2025.00211
Abstract
Epidemiological data on bacterial infections in cirrhosis in China remain limited. Therefore, we aimed to conduct a multicenter study to investigate the characteristics and outcomes
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Epidemiological data on bacterial infections in cirrhosis in China remain limited. Therefore, we aimed to conduct a multicenter study to investigate the characteristics and outcomes of patients with cirrhosis and bacterial infections in China.
We retrospectively enrolled 1,438 hospitalized adult patients with cirrhosis and bacterial or fungal infections from 24 hospitals across China between January 2018 and September 2024. Data on demographics, clinical features, microbiology, treatment, and outcomes were collected.
A total of 1,783 infection episodes were recorded, including 1,668 first infections and 115 second infections. Most infections were community-acquired (86.6%). Pneumonia was the most common infection type (26.7%), followed by spontaneous bacterial peritonitis (19.5%) and spontaneous bacteremia (14.1%). Among 754 pathogens isolated from 620 patients, Klebsiella pneumoniae (20.1%) was nearly as common as Escherichia coli (21.7%). Multidrug-resistant (MDR) organisms accounted for 41.0% of all isolates, with extended-spectrum β-lactamase-producing Escherichia coli being the most prevalent MDR strain (8.9% of patients). Adherence to empirical antibiotic treatment guidelines from the European Association for the Study of the Liver was significantly lower in this cohort compared to the global study (21.5% vs. 61.2%, P < 0.001), accompanied by a lower clinical resolution rate (63.5% vs. 79.8%, P < 0.001).
The clinical and microbiological characteristics of bacterial infections in patients with cirrhosis in China differ substantially from those reported in other regions. These findings highlight the need for region-specific management and prevention strategies, particularly in light of the changing microbiological landscape, high MDR prevalence, and suboptimal antibiotic practices.
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Open Access
Chemical Analysis of Polyphenolic Content and Antioxidant Screening of 17 African Propolis Samples Using RP-HPLC and Spectroscopy
Shankar Katekhaye, Bhagyashree Kamble, Ghaida Mustafa, James Fearnley, Anant Paradkar
Published online May 13, 2025
Future Integrative Medicine.
doi:10.14218/FIM.2025.00004
Abstract
Propolis is a resinous material produced by honeybees. Its chemical composition is highly complex and varies significantly depending on geographic region and season. This intrinsic
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Propolis is a resinous material produced by honeybees. Its chemical composition is highly complex and varies significantly depending on geographic region and season. This intrinsic variability presents challenges to the standardization and quality control of propolis. This study aimed to evaluate the chemical composition, total phenolic content, and antioxidant potential of propolis collected from seventeen geographical regions across Africa.
A reverse-phase high-performance liquid chromatography (RP-HPLC) method coupled with a photodiode array detector (PDA) was used for analysis of propolis samples. The flavonoid and phenolic contents of the samples were determined using colorimetric and Folin-Ciocalteu methods. Antioxidant capacity was assessed using the 2,2-diphenyl-1-picrylhydrazyl assay.
Five flavonoids (naringenin, pinocembrin, galangin, chrysin, and quercetin), one flavonoid glycoside (rutin), six phenolic acids (caffeic acid, p-coumaric acid, cinnamic acid, chlorogenic acid, ferulic acid, and gallic acid), and an aromatic ester - caffeic acid phenethyl ester were simultaneously detected and quantified using RP-HPLC with an ACE-5 C18 column (250 mm × 4.6 mm i.d., 5 µm) and PDA detector. The reference standards showed good linearity with regression coefficients (R2) ranging from 0.96 to 0.99. For precision, repeatability, and stability studies, the relative standard deviation for all reference standards was below 2.5%. The 2,2-diphenyl-1-picrylhydrazyl assay yielded EC50 values ranging from 17.6 ± 0.39 to 0.16 ± 0.001 mg/mL.
RP-HPLC method for the simultaneous quantification of thirteen reference standards will serve as a reliable tool for the standardization and quality evaluation of propolis. The flavonoid and phenolic contents are key contributors to the antioxidant activity of propolis and reflect local plant biodiversity and bee–plant interactions within the ecosystem.
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