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Case Report Open Access
Development and Successful Treatment of Spinal Mixed Histiocytosis in an Elderly Woman following Two Relapses of BRAF-mutated Unifocal Skull Langerhans Cell Histiocytosis
Tsuneyoshi Hamada, Miyako Kobayashi, Ayaka Fukui, Naoki Nakajima, Naoyuki Anzai, Shinsaku Imashuku
Published online March 23, 2026
Oncology Advances. doi:10.14218/OnA.2025.00030
Abstract
Development of mixed histiocytosis (Langerhans cell histiocytosis (LCH))/Erdheim–Chester disease (ECD)) after treatment in patients with an initial skull LCH lesion has not been [...] Read more.

Development of mixed histiocytosis (Langerhans cell histiocytosis (LCH))/Erdheim–Chester disease (ECD)) after treatment in patients with an initial skull LCH lesion has not been well recognized. An elderly woman initially developed LCH at the left temporal bone, preceded by polyuria and polydipsia five years earlier; the lesion was surgically removed. Two years thereafter, she experienced her first LCH relapse with a right parietal skull lesion, in which a BRAF V600E mutation was confirmed, and chemotherapy was initiated. After a second LCH relapse involving the left parietal bone, the patient presented with a third relapse at the L2 vertebra. This lesion was pathologically diagnosed as mixed histiocytosis (LCH/ECD), resulting in refractoriness to conventional chemotherapy, and was successfully treated with targeted therapy using BRAF and MEK inhibitors. Spinal mixed histiocytosis (LCH/ECD) may develop following relapses of skull LCH after chemotherapy, for which targeted therapy could be effective.

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Mini Review Open Access
The Role of Confocal Laser Endomicroscopy in Disorders of Gut–Brain Interaction: A Narrative Review
Borko Nojkov
Published online June 26, 2026
Journal of Translational Gastroenterology. doi:10.14218/JTG.2026.00009
Abstract
Disorders of gut–brain interaction (DGBIs) encompass some of the most common gastrointestinal disorders and affect up to 40% of the general population. Despite their inherent heterogeneity [...] Read more.

Disorders of gut–brain interaction (DGBIs) encompass some of the most common gastrointestinal disorders and affect up to 40% of the general population. Despite their inherent heterogeneity and diverse clinical manifestations, many of the underlying pathophysiological mechanisms overlap among different DGBIs. Activation of the gastrointestinal mucosal immune system at a low level (“low-grade inflammation”) and impairments in gut epithelial barrier structure and function have been reported to play a key role in the pathophysiology of multiple DGBIs, but these alterations cannot be detected using routine clinical testing. Confocal laser endomicroscopy (CLE) is an established, readily available technology that can be added to standard gastrointestinal endoscopy, enabling “real-time” microscopic evaluation of the gastrointestinal surface epithelium. CLE has been found to be capable of identifying gastrointestinal mucosal abnormalities that are reflective of epithelial barrier impairment and/or low-grade immune activation. Over the past several years, multiple intriguing studies have utilized CLE as a clinically applicable tool to evaluate the intestinal mucosa in patients with various DGBIs. The aim of this narrative review is to summarize the available literature on the role of CLE in patients with DGBIs and to provide a perspective on the use of this technology in DGBIs.

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Review Article Open Access
Ethnopharmacology in Combating Emerging Diseases: Lessons from COVID-19 in Nigeria
Emmanuel Agbamu, Triumph Balogun, Promise Kamsiyochukwu Okoro, Kabeerat Arike Balogun, Justinah Ekpoboredefe, Nduka Godsgift Iteh, Christabel Ebulu
Published online July 30, 2026
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2026.00004
Abstract
Emerging diseases are those that appear in a population for the first time or previously existed, but rapidly increase in incidence or geographic range. During the coronavirus disease [...] Read more.

Emerging diseases are those that appear in a population for the first time or previously existed, but rapidly increase in incidence or geographic range. During the coronavirus disease 2019 (COVID-19) pandemic, ethnopharmacological practices became prominent in Nigeria because herbal remedies were affordable, locally accessible, and supported by longstanding cultural trust. However, despite broad public use and some regulatory progress, evidence for the safety, efficacy, standardization, and clinical application of these remedies remains limited. This narrative review examines the integration of ethnopharmacology into Nigeria’s COVID-19 response, evaluates its strengths, constraints, and lessons, and considers future pathways for incorporating ethnopharmacological practices into epidemic preparedness and response strategies. It reviews literature and regulatory information published from 2015 to 2025, focusing on herbal remedies used during the pandemic, regulatory listing processes, and key research gaps. Common remedies were derived from Zingiber officinale, Allium sativum, Citrus limon, Curcuma longa, and Garcinia kola. The National Agency for Food and Drug Administration and Control in Nigeria accelerated toxicological testing and listed 14 local herbal medicines, including Pax Herbal Cugzin, Niprimune, and IHP Detox Tea. This established a baseline safety for human consumption but did not validate therapeutic efficacy against severe acute respiratory syndrome coronavirus 2, which requires rigorous clinical trials. Although some formulations showed promising findings in preliminary clinical, in silico, and in vitro studies, the evidence was constrained by small pilot samples, absence of multiphase randomized controlled trials, insufficient in vivo pharmacokinetic data, and difficulties in isolating active compounds necessary for batch-to-batch consistency. Strengthening Nigeria’s resilience to future epidemics will require sustained investment in scientific research infrastructure, toxicogenomic and metabolomic studies, robust intellectual property frameworks for indigenous knowledge, and transparent public communication to reduce misinformation and product misuse.

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Research Letter Open Access
Global Burden and Trends of Cervical Cancer in Spain Based on GBD 2023
Javier Guinea-Castanares, Jesus Iturralde-Iriso, Gloria Martinez-Iniesta, Irune Elizondo-Pinillos, Carolina Paez-Salemi
Published online March 23, 2026
Cancer Screening and Prevention. doi:10.14218/CSP.2025.00031
Original Article Open Access
Application of A New Combined Surgical Strategy in Spontaneous Supratentorial Intracerebral Hemorrhage: A Retrospective Cohort Study
Zhiyang Li, Jiajun Wei, Wenju Wang, Minghui Lu, Zohaib Shafiq, Qiuwei Hua, Long Zhou, Ping Song, Qiang Cai
Published online March 28, 2026
Neurosurgical Subspecialties. doi:10.14218/NSSS.2025.00043
Abstract
The optimal surgical management for spontaneous supratentorial intracerebral hemorrhage (SSICH) remains controversial because conventional approaches often fail to balance rapid [...] Read more.

The optimal surgical management for spontaneous supratentorial intracerebral hemorrhage (SSICH) remains controversial because conventional approaches often fail to balance rapid decompression with effective hematoma evacuation. This study aimed to evaluate the efficacy and safety of new combined surgical strategies (“two-in-one” and “three-in-one”) versus conventional methods for SSICH.

This retrospective cohort study included 451 SSICH patients treated between January 2019 and December 2023. Based on clinical severity, patients were stratified into Group I (non-herniation, n = 374) and Group II (herniation, n = 77). Within each subgroup, patients were further categorized by treatment period: a historical control cohort (2019–2020) receiving conventional surgery, and an intervention cohort (2021–2023) receiving combined strategies (“two-in-one” for Group I; “three-in-one” for Group II). Outcomes included decompression time, hematoma evacuation rate, complications, and six-month functional recovery (Glasgow Outcome Scale/modified Rankin Scale), were compared.

In Group I, the “two-in-one” strategy achieved faster decompression (4.65 min) and a high evacuation rate (92.15%), which was comparable to neuroendoscopy alone (90.58%) and significantly higher than stereotactic aspiration alone (44.55%). This was associated with improved six-month outcomes (poor outcome rates were 39.39%, 54.35%, and 42.86% in Groups I-A, I-B, and I-C, respectively, overall P = 0.034). In Group II, the “three-in-one” strategy demonstrated shorter decompression time (4.73 vs. 37.85 min, P < 0.001) and higher evacuation rates (80.51% vs. 63.50%, P < 0.001) than decompressive craniectomy alone. Logistic regression further supported the prognostic advantage of the “two-in-one” strategy in Group I.

These combined strategies may integrate the advantages of multiple techniques to enable rapid decompression and effective hematoma clearance in SSICH. Prospective studies are warranted.

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Review Article Open Access
Circular RNAs and Gut Barrier Integrity: Molecular Mechanisms and Translational Applications
Wanglei Yang, Jiaqi Lou
Published online March 25, 2026
Gastroenterology & Hepatology Research. doi:10.14218/GHR.2026.00005
Abstract
The intestinal barrier, a critical interface between the body and the external environment, is essential for maintaining internal homeostasis. Comprising mechanical, chemical, immune, [...] Read more.

The intestinal barrier, a critical interface between the body and the external environment, is essential for maintaining internal homeostasis. Comprising mechanical, chemical, immune, and biological components, its dysfunction underpins multiple gastrointestinal pathologies. Circular RNAs (circRNAs), covalently closed non-coding RNAs, have emerged as central regulators of gut barrier homeostasis. This review synthesizes advances in circRNA roles in intestinal stem cell renewal, apoptosis-proliferation balance, microbiome interactions, and immune regulation. Key findings highlight circRNA networks operating via competitive endogenous RNA mechanisms, protein interactions, and translational potential to influence barrier function. We further discuss circRNAs as diagnostic biomarkers in inflammatory bowel disease and their therapeutic potential in barrier-related pathologies. Advances in RNA nanotechnology (e.g., lipid nanoparticles) and synthetic biology position engineered circRNAs as next-generation therapies for precision intervention in gastrointestinal disorders. Importantly, this review also critically examines the current limitations of these translational approaches, including delivery challenges, safety considerations, and the preliminary nature of many preclinical findings, providing a balanced perspective on the path from bench to bedside.

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Guideline Open Access
Evidence-based Guideline on the Standardized Diagnostic Imaging Report for Pancreatic Solid Tumors in China
Yun Bian, Jing Li, Zhaoshen Li, Jianping Lu, Chengwei Shao, Shiyuan Liu, Min Chen, Xun Li, on behalf of the Professional Committee of Pancreatic Diseases, Chinese Medical Doctor Association; the Radiology Branch of the Chinese Medical Association; the National Clinical Research Center for Digestive Diseases (Shanghai); and the Shanghai Medical Association Radiology Quality Control Center
Published online March 28, 2026
Cancer Screening and Prevention. doi:10.14218/CSP.2025.00029
Abstract
Pancreatic solid tumors encompass diverse pathological subtypes. Objective, accurate, and comprehensive imaging examinations and diagnostic reports are essential for preoperative [...] Read more.

Pancreatic solid tumors encompass diverse pathological subtypes. Objective, accurate, and comprehensive imaging examinations and diagnostic reports are essential for preoperative staging, treatment planning, and prognostic evaluation. Currently, China lacks corresponding guidelines or consensus documents, leading to prominent issues including subjective diagnostic reports, incomplete descriptions, and inconsistent terminology. The present guideline was developed to standardize diagnostic imaging reporting of pancreatic solid tumors in China. Relevant domestic and international evidence on imaging examination techniques, key reporting elements, and diagnostic criteria was systematically reviewed and synthesized. This guideline was developed by a multidisciplinary expert panel through systematic evidence retrieval and appraisal, GRADE-based recommendation grading, modified Delphi consensus, and external review. A total of 20 evidence-based recommendations, 13 strong and 7 weak, were formulated, in aspects of imaging examination and diagnostic reporting standards, including the measurement of the tumor size of pancreatic solid tumors, assessment of the obstruction of the main pancreatic duct and common bile duct, definition, assessment, and clinical significance of pancreatic parenchymal atrophy, the assessment of obstructive acute pancreatitis, pseudocysts/retention cysts, and peripancreatic vessels, criteria for resectability, regional lymph node assessment, criteria for suspicious lymph nodes and descriptions of their specific location, and detection of hepatic and peritoneal metastases. Implementation of this guideline in clinical practice will help standardize the accuracy and consistency of diagnostic imaging reports for pancreatic solid tumors in China, thereby advancing standardized imaging diagnosis and informing clinical treatment decisions.

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Hypothesis Open Access
A Peptide-targeted, Hypoxia-responsive Adeno-associated Virus Platform for Tumor-selective Delivery of Chemokines and RNAi in Non-small Cell Lung Cancer: A Hypothesis
Dong-woo Han, Eunjoo H. Lee
Published online April 28, 2026
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2026.00009
Abstract
Adeno-associated virus (AAV) vectors have favorable safety and durable transgene expression but are limited in oncology by insufficient tumor specificity and off-target expression. [...] Read more.

Adeno-associated virus (AAV) vectors have favorable safety and durable transgene expression but are limited in oncology by insufficient tumor specificity and off-target expression. Tumor hypoxia and non-small cell lung cancer (NSCLC)-associated surface ligands offer complementary layers of biological selectivity for more precise gene delivery. This study proposes an NSCLC-directed, hypoxia-responsive AAV architecture that integrates MGS4-guided capsid targeting with dual hypoxia-responsive element (HRE)-gated promoters driving glutamine-modified C-X-C motif chemokine ligand 9-fragment crystallizable region fusion protein (Q-CXCL9-Fc) expression and baculoviral IAP repeat containing 5 (BIRC5)-linked mesothelin (MSLN) silencing. We conceptually designed an AAV vector that combines three layers of NSCLC selectivity: MGS4-guided capsid targeting, hypoxia-gated transcription, and tumor-active promoter control. The capsid displays the MGS4 peptide, isolated by phage display biopanning as a high-affinity ligand for the lung squamous cell carcinoma cell line HCC15 and later shown to internalize into a substantial fraction of NSCLC cell lines and bind a subset of human NSCLC biopsy samples, indicating activity across multiple NSCLC subtypes. The genome encodes Q-CXCL9-Fc under a 4× HRE-cytomegalovirus promoter to sustain C-X-C motif chemokine receptor 3-dependent T-cell recruitment and a miR-30-based short hairpin RNA targeting MSLN under a 4× HRE-BIRC5 promoter to inhibit tumor progression. This architecture is hypothesized to enrich AAV entry into NSCLC lesions via MGS4 while restricting Q-CXCL9-Fc secretion and MSLN silencing to hypoxic, BIRC5-active tumor regions, enabling synergistic enhancement of antitumor immunity and suppression of tumor-intrinsic pathways. The proposed multimodal, hypoxia-responsive AAV platform represents a conceptual precision oncology strategy that couples environmental sensing, tumor-specific transcription, and peptide-defined tropism within a single vector and could inform next-generation NSCLC-directed AAV systems.

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Original Article Open Access
New Neuroendocrine Markers PITX2, PHOX2B, and HAND2 Do Not Offer Diagnostic Utility in Fine-needle Aspiration Biopsies of Primary and Secondary Medullary Thyroid Carcinomas: A Retrospective Multi-institutional Study
Mari Helenius, David Kalfert, Zahra Maleki, Güliz A. Barkan, Esther Diana Rossi, Guoping Cai, Ivana Kholová
Published online June 16, 2026
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2026.00011
Abstract
Medullary thyroid carcinoma (MTC) is a neuroendocrine malignancy arising from parafollicular C-cells with known variations in cytomorphologic and immunophenotypic features. New [...] Read more.

Medullary thyroid carcinoma (MTC) is a neuroendocrine malignancy arising from parafollicular C-cells with known variations in cytomorphologic and immunophenotypic features. New neuroendocrine markers pituitary homeobox 2 (PITX2), paired-like homeobox 2B (PHOX2B), and heart and neural crest derivatives expressed 2 (HAND2) have recently been introduced, but studies using these markers in MTC are limited. The aim of this study was to evaluate the expression and potential diagnostic utility of PITX2, PHOX2B, and HAND2 in primary and secondary MTCs and to compare their expression with chromogranin A, synaptophysin, insulinoma-associated protein 1 (INSM1), and calcitonin.

A total of 34 histologically confirmed cases of MTC with available cell blocks were included. Sixteen MTC samples were fine-needle aspirates from primary thyroid lesions, and eighteen were from secondary metastatic lesions. Twelve samples from thyroid carcinomas of follicular origin were included as controls.

PITX2 positivity was observed in 17 (50.0%) MTC samples and in 4 (33.3%) control samples (P = 0.502). PITX2 positivity was found in 43.8% of primary thyroid MTC lesions and in 55.6% of secondary MTC lesions (P = 0.366). Co-expression of PITX2 with chromogranin A, synaptophysin, INSM1, and calcitonin was observed. PHOX2B and HAND2 were negative in all MTC and control samples.

There were no significant differences in PITX2 expression between primary and secondary MTC samples. PITX2 did not show reliable utility in distinguishing MTC from thyroid carcinomas of follicular origin. PHOX2B and HAND2 were negative in all samples. These results suggest that these new markers do not offer diagnostic value for MTC as stand-alone markers or as additions to the diagnostic workup panel.

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Research Letter Open Access
Real-world Effectiveness and Safety of Coblopasvir plus Sofosbuvir in the Treatment of Chronic Hepatitis C Infection in Wenzhou, Eastern China: A Multicenter Observational Study
Li-Min Ruan, Xiao-Cheng Zhang, Xin-Yu Zhang, Qing-Qing Zhou, Qiong-Na Zheng, Chang-Long Fu, Yi-Bing Hu, Yu Zhou, Yang-He Wu
Published online March 12, 2026
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00673
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