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Review Article Open Access
Xin Quan, Hua Wen, Hao Liang, Mingxin Zhang
Published online September 25, 2024
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Cancer Screening and Prevention. doi:10.14218/CSP.2024.00018
Abstract
Among all tumors worldwide, digestive tract tumors have a higher incidence rate and a significant disease burden. Esophageal cancer, gastric cancer, liver cancer, and colorectal [...] Read more.

Among all tumors worldwide, digestive tract tumors have a higher incidence rate and a significant disease burden. Esophageal cancer, gastric cancer, liver cancer, and colorectal cancer are often diagnosed at an advanced stage, and the prognosis remains poor. Currently, tumor treatment resistance is a major global challenge, with many underlying mechanisms. Ferroptosis has been shown to reverse drug resistance. This article reviews the mechanisms and recent advancements in ferroptosis related to reversing treatment resistance in gastrointestinal tumors, aiming to provide theoretical insights and research directions for the diagnosis and treatment of digestive tract tumors.

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Original Article Open Access
Tongtong Li, Xuan Shen, Tao Zhang, Jiaheng Ren, Wang Wang, Didi Wang, Pengxia Zhang
Published online April 18, 2025
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00369
Abstract
Hepatocellular carcinoma (HCC) remains challenging to treat in advanced stages, primarily due to the development of resistance to sorafenib. There is an urgent need for novel therapeutic [...] Read more.

Hepatocellular carcinoma (HCC) remains challenging to treat in advanced stages, primarily due to the development of resistance to sorafenib. There is an urgent need for novel therapeutic strategies to overcome this resistance. This study aimed to investigate the potential of oleanolic acid (OA), a natural hepatoprotective compound, in mitigating sorafenib resistance and elucidate its underlying molecular mechanisms.

Sorafenib-resistant Huh7 and HepG2 cell lines were established to mimic the resistant phenotype. The effects of OA on these cells were evaluated by assessing cell invasion, migration, and sensitivity to sorafenib. Gene expression analysis was conducted to identify molecular changes induced by OA treatment, with a focus on fabp3 expression.

Oleanolic acid significantly inhibited the invasive and migratory capabilities of sorafenib-resistant Huh7 and HepG2 cells (p < 0.01). Furthermore, OA treatment downregulated fabp3 expression and restored the cells’ sensitivity to sorafenib.

Oleanolic acid shows promise as an adjunct therapy for overcoming sorafenib resistance in HCC. By reducing cell aggressiveness and restoring drug sensitivity, OA may enhance the therapeutic efficacy of current treatments for advanced HCC.

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Original Article Open Access
Daniela Senra, Nara Guisoni, Luis Diambra
Published online April 25, 2025
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Gene Expression. doi:10.14218/GE.2024.00071
Abstract
Tumors are complex systems characterized by variations across genetic, transcriptomic, phenotypic, and microenvironmental levels. This study introduced a novel framework for quantifying [...] Read more.

Tumors are complex systems characterized by variations across genetic, transcriptomic, phenotypic, and microenvironmental levels. This study introduced a novel framework for quantifying cancer cell heterogeneity using single-cell RNA sequencing data. The framework comprised several scores aimed at uncovering the complexities of key cancer traits, such as metastasis, tumor progression, and recurrence.

This study leveraged publicly available single-cell transcriptomic data from three human breast cancer subtypes: estrogen receptor-positive, human epidermal growth factor receptor 2-positive, and triple-negative. We employed a quantitative approach, analyzing copy number alterations (CNAs), entropy, transcriptomic heterogeneity, and diverse protein-protein interaction networks (PPINs) to explore critical concepts in cancer biology.

We found that entropy and PPIN activity related to the cell cycle could distinguish cell clusters with elevated mitotic activity, particularly in aggressive breast cancer subtypes. Additionally, CNA distributions varied across cancer subtypes. We also identified positive correlations between the CNA score, entropy, and the activities of PPINs associated with the cell cycle, as well as those linked to basal and mesenchymal cell lines.

This study addresses a gap in the current understanding of breast cancer heterogeneity by presenting a novel quantitative approach that offers deeper insights into tumor biology, surpassing traditional marker-based methods.

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Original Article Open Access
Yusuf Musa, Abubakar Sadiq Maiyaki, Yusuf Shehu Umar, Pantong Mark Davwar, Kolawole Oluseyi Akande, Chinwe Philomena Onyia, Kenechukwu Chukwuemeka Okonkwo, Muhammad Manko, Adamu Alhaji Samaila
Published online December 25, 2024
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Journal of Translational Gastroenterology. doi:10.14218/JTG.2024.00010
Abstract
Gastrointestinal endoscopy has revolutionized the entire practice of gastroenterology worldwide, including Nigeria. Endoscopy was introduced in Nigeria more than four decades ago, [...] Read more.

Gastrointestinal endoscopy has revolutionized the entire practice of gastroenterology worldwide, including Nigeria. Endoscopy was introduced in Nigeria more than four decades ago, and it has been a story of varying successes and challenges. This study explored the various experiences of endoscopists, the challenges they face, and the efforts put in place to maintain the practice in Nigeria.

This cross-sectional survey was conducted from October to December 2023 among endoscopists practicing in Nigeria. It involved a 30-part self-administered online questionnaire that inquired about individual experiences in endoscopy practice. These included qualifications, competency, facility settings, challenges faced, and innovations employed to address them. At the end of the survey, responses were analyzed using descriptive statistics, Chi-square, and likelihood ratios at the 0.05 level of significance.

A total of 41 respondents participated in the survey from 19 states across the six geopolitical zones of Nigeria, with a mean age ± standard deviation of 43 ± 7 years. Male respondents made up 80.5%, with Nigerian-trained gastroenterologists via the residency program constituting the predominant population, and an average endoscopy experience of five to nine years (39.02%). Most of the respondents work in public institutions (73.17%), with 43.9% working in at least two centers. There was an average of five endoscopists and three to seven endoscopy centers per state. Most centers perform 11–12 upper and four to five lower GI endoscopies per week, respectively, with a predominance of diagnostic procedures. The most common endoscopic intervention was variceal band ligation. The most common challenge faced was the high cost of procedures, accessories, and maintenance of endoscopes.

Endoscopy practice cuts across all the zones and most states of the federation. Both diagnostic and therapeutic procedures are available in most centers. However, the practice is faced with a myriad of challenges, mainly poor financing and inadequate training, among others. As a result, some innovations were locally developed to ease the practice and prevent it from collapsing.

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Original Article Open Access
Momina Ahsan, Fareeha Adnan, Moiz Ahmed Khan, Nazia Khursheed
Published online March 25, 2025
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Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2025.00001
Abstract
Escalating antimicrobial resistance is a global threat, emphasizing the need to explore alternative treatment options. Hence, we aimed to explore the in-vitro activity of ceftazidime-avibactam [...] Read more.

Escalating antimicrobial resistance is a global threat, emphasizing the need to explore alternative treatment options. Hence, we aimed to explore the in-vitro activity of ceftazidime-avibactam (CAZ-AVI) in clinical isolates of carbapenem-resistant gram-negative bacteria.

This was an observational, cross-sectional study conducted at the Microbiology Department of Indus Hospital, Karachi, Pakistan, from January 2023 to October 2024. Carbapenem-resistant gram-negative rods isolated from clinical specimens received from the outpatient, emergency, and inpatient departments were included. Consecutive, non-probability sampling was employed for the collection of isolates. Identification of the organisms was confirmed using API® ID strips, and antimicrobial susceptibility for carbapenems and CAZ-AVI was determined via the Kirby-Bauer disc diffusion method.

A total of 158 bacterial isolates were characterized as carbapenem-resistant. Of these, 92 (58%) were Enterobacterales, and 66 (42%) were Pseudomonas aeruginosa. CAZ-AVI was susceptible in 17 (11%) of the isolates, of which four (24%) were Klebsiella spp. and Escherichia coli each, and nine (52%) were P. aeruginosa. CAZ-AVI-susceptible strains were predominant among patients aged 26–50 years (n = 6; 35%), most of whom were females (n = 10; 59%) and inpatients (n = 8; 47%). Clinical samples from patients with urinary tract infections grew the most CAZ-AVI-susceptible strains (n = 9; 53%).

Our study demonstrated low CAZ-AVI susceptibility in our carbapenem-resistant gram-negative bacterial strains. Understanding regional antimicrobial patterns in multidrug-resistant bacteria is crucial for the effective use of CAZ-AVI, along with the strict implementation of strategies for controlling antimicrobial resistance.

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Original Article Open Access
Zijie Xu, Wei Li, Wenli Li, Dalei Jiang, Quanjiang Dong, Lili Wang
Published online October 17, 2024
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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 [...] Read more.

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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Review Article Open Access
Jing Li, Huanhuan Wang, Jie Lin, Aili Wang, Shuiyin Miao, Huaie Liu
Published online May 13, 2025
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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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Case Report Open Access
Xinyu Yu, Weiming Xu
Published online February 28, 2025
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Neurosurgical Subspecialties. doi:10.14218/NSSS.2025.00001
Abstract
Balamuthia mandrillaris is a free-living amoeba that can cause granulomatous amoebic encephalitis, a lethal neurological condition in humans. This pathogen infects not only immunocompromised [...] Read more.

Balamuthia mandrillaris is a free-living amoeba that can cause granulomatous amoebic encephalitis, a lethal neurological condition in humans. This pathogen infects not only immunocompromised hosts but, more commonly, immunocompetent individuals. Balamuthia mandrillaris mainly infects the skin and nervous system. When it affects the nervous system, it can manifest as Balamuthia mandrillaris encephalitis (BAE). This article presents a case of BAE in central China, diagnosed through next-generation sequencing and histopathology. The patient is a 64-year-old male who was admitted to the Department of Neurosurgery with a one-week history of headache. Magnetic resonance imaging scans revealed a mass in the right temporal-occipital region, and postoperative pathological examination confirmed that the lesion was BAE. We will detail the clinical course of this disease in this patient, aiming to enhance clinicians’ understanding of Balamuthia mandrillaris infections.

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Mini Review Open Access
Hongyan Liu, Hao Ai, Ying Liu
Published online March 30, 2025
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Oncology Advances. doi:10.14218/OnA.2024.00034
Abstract
Endometrial cancer (EC) is one of the most prevalent malignancies of the female reproductive system and ranks among the three primary types of gynecological cancers. Recent trends [...] Read more.

Endometrial cancer (EC) is one of the most prevalent malignancies of the female reproductive system and ranks among the three primary types of gynecological cancers. Recent trends indicate a rising incidence of EC in younger patients, highlighting the urgent need for effective early screening strategies. This review examines the challenges associated with early diagnosis and screening, including ambiguous methodologies (e.g., transvaginal ultrasound: sensitivity 80–90%, specificity 60–70%), undefined target populations, and the absence of efficient, cost-effective, minimally invasive solutions (e.g., cytology sensitivity ≤50% in community settings). The article provides an overview of the current landscape and emerging innovations in universal EC screening, highlighting advancements in early detection and diagnosis, such as DNA methylation panels (sensitivity 89–94%, specificity 91–97% in phase II trials) and vibrational spectroscopy (sensitivity 92%, specificity 88% in pilot studies). Additionally, future directions for implementing effective screening strategies are explored, emphasizing the potential of high-accuracy biomarkers and scalable technologies to reduce mortality and healthcare costs.

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Case Report Open Access
Zhaoyang Yang, Bin Wang, Liang Yang, Xuemin Xue, Jiacong Wei, Liyan Xue
Published online October 30, 2024
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Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00033
Abstract
Paget’s disease of the esophagus is extremely rare, with few cases reported. In this report, we describe a case of recurrent esophageal Paget’s disease coexisting with small cell [...] Read more.

Paget’s disease of the esophagus is extremely rare, with few cases reported. In this report, we describe a case of recurrent esophageal Paget’s disease coexisting with small cell carcinoma. A 63-year-old man presented with the chief complaint of a rediscovered early esophageal cancer. Endoscopic examination revealed two separate superficial flat tumors in the upper and mid esophagus. Endoscopic submucosal dissection was performed, diagnosing diffuse Paget’s disease (5.5 × 3.5 cm) and a small focus on intramucosal squamous cell carcinoma, respectively. Paget’s cells were also found in the distal and right margins of the first specimen of endoscopic submucosal dissection. Immunohistochemical analysis showed that Paget’s disease diffusely expressed cytokeratin 7 (CK7), CK18, and mucin 6 (MUC6), and focally expressed CD56 and chromogranin A, but not CK5/6, p63, p40, MUC5AC, MUC2, or synaptophysin. A complete absence of p53 and Rb1 was observed in Paget’s disease. However, overexpression of p53 and retention of Rb1 were seen in squamous cell carcinoma. Approximately 27 months later, a prominent tumor was found at the same location as the previous Paget’s disease. Subsequently, radical surgery was performed, and the final pathological evaluation revealed esophageal small cell carcinoma coexisting with Paget’s disease. Moreover, both p53 and Rb1 were completely absent in both Paget’s disease and the small cell carcinoma. This suggests that esophageal Paget’s disease may dedifferentiate and develop into small cell carcinoma. In conclusion, esophageal Paget’s disease can co-occur with invasive carcinomas, including small cell carcinoma, and should be completely resected endoscopically, with close follow-up.

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