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Research Letter Open Access
Impact of Prolonged Ischemia and Fixation on the Immunohistochemical Expression of PD-L1 in Non-small Cell Lung Cancer Specimens
Angels Barberà, Juan González, Montserrat Martin, Pedro Luis Fernández, Albert Oriol, Fina Martínez-Soler, Tomas Santalucia, Jose Luis Mate
Published online March 18, 2026
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2025.00038
Original Article Open Access
Chronotype and Daytime Sleepiness in Women with Hashimoto’s Thyroiditis: A Cross-sectional Pilot Study
Zrinka Biloglav, Snježana Džijan, Darko Katalinić, Davor Lešić, Marko Bebek, Igor Žabić, Natko Gereš, Ivana Škrlec
Published online April 8, 2026
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2025.00071
Abstract
Hashimoto’s thyroiditis (HT), an autoimmune disease with a prevalence 2–7 times higher in women than in men, is associated with daytime sleepiness. The present study aimed to test [...] Read more.

Hashimoto’s thyroiditis (HT), an autoimmune disease with a prevalence 2–7 times higher in women than in men, is associated with daytime sleepiness. The present study aimed to test the hypothesis that thyroid function is associated with chronotype and daytime sleepiness in women with HT.

This retrospective cross-sectional study included women with confirmed HT. Demographic, clinical and laboratory data were collected. The reduced Morningness-Eveningness Questionnaire (rMEQ) and the Epworth Sleepiness Scale (ESS) were used to assess chronotype and daytime sleepiness, respectively. Based on rMEQ, women were categorized as having a morning (≥18), intermediate (12–17) or evening (≤11) chronotype. Based on ESS, women were categorized as having normal or increased daytime sleepiness.

Overall, 106 women, aged 43 ± 12 years, were included. Most had normal daytime sleepiness (68.9%), and the majority had an intermediate chronotype (61.3%), while only one had a morning chronotype (0.9%). Age was significantly associated with chronotype (P = 0.026). There was a significant association between chronotype and thyroglobulin antibodies (TgAb, P = 0.012). Free triiodothyronine (fT3) levels were significantly higher in women with an evening chronotype than in those with an intermediate chronotype (P = 0.045; OR = 0.500; 95% CI 0.25–0.98). Daytime sleepiness was significantly associated with TgAb (P = 0.016) and thyroid-stimulating hormone (TSH, P = 0.040). TgAb levels were significantly higher in women with increased daytime sleepiness (P = 0.049, OR = 1.003, 95% CI 1.00–1.01) than in those with normal daytime sleepiness.

Approximately one-third of women have an evening chronotype, and approximately one-third had increased daytime sleepiness. TgAb, fT3, and TSH are associated with daytime sleepiness or chronotype in women with HT. Further investigation is required for the underlying mechanisms.

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Original Article Open Access
Biochemical Markers Indicating a High Risk for Infectious Complications in Patients with Combined Traumatic Brain Injury: A Retrospective Observational Study
Ozal Beylerli, Hongli Zhang, Elmar Musaev, Revaz Dzhindzhikhadze, Ravil Biktimirov, Vadim Rashidov, Ilgiz Gareev
Published online December 31, 2025
Neurosurgical Subspecialties. doi:10.14218/NSSS.2025.00042
Abstract
Combined traumatic brain injury (CTBI) remains a leading cause of disability/mortality among workers, yet which routine biochemical tests that predict infectious complications remain [...] Read more.

Combined traumatic brain injury (CTBI) remains a leading cause of disability/mortality among workers, yet which routine biochemical tests that predict infectious complications remain controversial. We aimed to identify the most informative serum markers for early diagnosis and prognosis of such complications.

In this retrospective observational study, 80 acute CTBI patients (40 without vs. 40 with mainly bacterial infectious complications) and 40 healthy controls were analyzed. Serum collected at 24, 72, and 168 h was assayed for protein fractions, metabolic markers, lipid peroxidation indices, antioxidant activity, endogenous intoxication markers, acids/minerals, and relevant enzymes.

The study found that the most important prognostic indicator for infectious complications was a simultaneous increase in α1-globulins, β-globulins, diene conjugates, superoxide dismutase, medium- and low-molecular-weight substances in erythrocytes, erythrocyte oligopeptides, and lactate at 24 h after injury (p < 0.001). A significant increase in sialic acids, uronic acids, total Ca and P, and low-density lipoproteins was observed at 72 h after injury (p < 0.001). Notably, individual components from the 24-h panel demonstrated high standalone predictive value, with areas under the curve of diene conjugates (0.91), erythrocyte oligopeptides (0.87), β-globulin (0.86), α1-globulin (0.82), and superoxide dismutase (0.82), respectively. The elevation of these biomarker profiles was significantly correlated with worse clinical outcomes, including longer intensive care unit stay and ventilation duration.

This study identified a set of biochemical markers associated with infectious complications in patients with CTBI. These biochemical parameters may serve as additional diagnostic and prognostic criteria for the management of infectious complications in patients with СTBI.

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Case Report Open Access
A Case of Invasive Pituitary Prolactinoma Misdiagnosed as Nasopharyngeal Carcinoma: Diagnostic Lessons and Management
Qiang Liu, Yibin Zeng, Kang Qian, Xing Huang, Hongyang Zhao, Xiaobing Jiang, Haijun Wang
Published online December 31, 2025
Neurosurgical Subspecialties. doi:10.14218/NSSS.2025.00044
Abstract
Invasive pituitary adenomas with infrasellar extension can present with symptoms such as epistaxis and nasal obstruction, closely mimicking the clinical and radiological characteristics [...] Read more.

Invasive pituitary adenomas with infrasellar extension can present with symptoms such as epistaxis and nasal obstruction, closely mimicking the clinical and radiological characteristics of nasopharyngeal carcinoma, which frequently leads to misdiagnosis. This report discusses the case of a 32-year-old male who was initially misdiagnosed with nasopharyngeal carcinoma for approximately one month and subsequently underwent radiotherapy and chemotherapy. However, a multidisciplinary assessment at our institution, incorporating magnetic resonance imaging findings of an invasive sellar mass, serum prolactin levels exceeding 2,000 ng/mL, and positive immunohistochemistry for PIT-1 and prolactin, established the diagnosis of an invasive prolactinoma. Treatment with bromocriptine led to significant tumor reduction. However, this was complicated by cerebrospinal fluid leakage, which subsequently resulted in an intracranial infection. The patient underwent surgical resection of the tumor and repair of the cerebrospinal fluid leak, with postoperative pathology confirming a PIT1-lineage, densely granulated, prolactin-secreting adenoma. The patient experienced a favorable recovery, with prolactin levels normalizing under continued bromocriptine therapy. This case highlights the critical importance of routine hormonal screening, thorough evaluation of nasopharyngeal mucosal integrity, and multidisciplinary collaboration in the diagnostic process.

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Original Article Open Access
Efficacy of Sequential Transarterial Chemoembolization after Stereotactic Body Radiation Therapy versus Radiation Therapy Alone for Recurrent Hepatocellular Carcinoma: A Propensity Score-matched Analysis
Jian-Hui Wu, Jun-Qiang Ding, Jing Sun, Wei-Ping He, Xue-Zhang Duan, Wen-Gang Li
Published online March 13, 2026
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00568
Abstract
Comparative data on sequential transarterial chemoembolization (TACE) after stereotactic body radiation therapy (SBRT) in recurrent hepatocellular carcinoma (HCC) remain limited. [...] Read more.

Comparative data on sequential transarterial chemoembolization (TACE) after stereotactic body radiation therapy (SBRT) in recurrent hepatocellular carcinoma (HCC) remain limited. This study aimed to evaluate the efficacy of this combination.

We retrospectively reviewed 152 patients with recurrent HCC who met predefined eligibility criteria; 109 received SBRT alone and 43 received SBRT plus TACE. To minimize selection bias, a 2:1 propensity score matching was performed, resulting in 68 patients in the SBRT-alone group and 36 in the SBRT plus TACE group for the final comparative analysis. Overall survival, progression-free survival, and local control were assessed using the Kaplan-Meier method.

The SBRT plus TACE group was associated with numerically higher survival rates, although this difference did not reach statistical significance. The cumulative one-, three-, and five-year overall survival rates were 91.2%, 76.3%, and 61.8% for SBRT alone, compared to 100.0%, 86.1%, and 77.5% for the combination therapy ( p = 0.069). The corresponding progression-free survival rates were 73.1%, 51.1%, and 32.3% versus 88.9%, 58.1%, and 52.3% ( p = 0.091). No acute grade ≥3 toxicities were observed in either group.

In this exploratory analysis of recurrent HCC, the combination of SBRT and TACE demonstrated a favorable trend toward improved survival compared with SBRT alone, without an increase in severe toxicity. While these findings did not reach statistical significance, they establish the safety profile of the combined approach and provide preliminary evidence supporting its potential therapeutic role. This hypothesis-generating study justifies and informs the design of larger, prospective trials to definitively evaluate the efficacy of this regimen.

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Original Article Open Access
LDLR+ Monocytic Myeloid-derived Suppressor Cells Attenuate Allograft Rejection in Liver Transplantation
Xin Zhou, Xinqiang Li, Peng Jiang, Shipeng Li, Zhuoyu Jia, Xueteng Wang, Hailun Cai, Huan Liu, Ruidong Ding, Jinzhen Cai
Published online February 27, 2026
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00621
Abstract
Liver transplant rejection significantly affects patient prognosis. Myeloid-derived suppressor cells (MDSCs), known for their potent immunoregulatory functions, represent a promising [...] Read more.

Liver transplant rejection significantly affects patient prognosis. Myeloid-derived suppressor cells (MDSCs), known for their potent immunoregulatory functions, represent a promising target for managing liver transplant rejection. This study aimed to systematically characterize the diversity of MDSC subsets and their context-dependent functions, particularly within the context of transplant tolerance.

We analyzed clinical and murine liver transplants using single-cell RNA sequencing, bulk RNA sequencing, flow cytometry, multiplex immunohistochemistry, and co-culture assays to phenotype MDSC subsets.

Single-cell RNA sequencing analysis of human and murine samples revealed MDSC involvement in transplant rejection. In mice, MDSC scores followed a normal distribution during the first week post-transplant and correlated with clinical flow cytometry data at one month. A distinct LDLR+ monocytic MDSC (M-MDSC) subset was identified and confirmed through spatial mapping by multiplex immunohistochemistry. Flow cytometry demonstrated dynamic changes in LDLR+ M-MDSCs across tissues (liver, spleen, peripheral blood, bone marrow, and lymph nodes), with a peak during acute rejection. Co-culture experiments showed that LDLR−/− M-MDSCs exhibited reduced Arg-1/iNOS expression and an impaired capacity to induce inhibitory receptors (TIGIT, PD1, CTLA-4) or suppress effector molecules (GZMB, IFN-γ, IL-2) in CD8+ T cells.

These findings highlight the critical role of MDSCs in liver transplant rejection. LDLR+ M-MDSCs exhibited enhanced immunosuppressive properties, underscoring their potential clinical relevance in mitigating rejection and promoting immune tolerance.

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Corrigendum Open Access
Corrigendum: Antioxidant-enzyme Interaction in Non-communicable Diseases
Benjamin O. Ezema, Chijioke Nwoye Eze, Thecla Okeahunwa Ayoka, Charles Okeke Nnadi
Published online July 15, 2025
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2024.00020C
Original Article Open Access
Intestinal Candida albicans is Associated with Subclinical Coronary Atherosclerosis in Metabolic Dysfunction-associated Steatotic Liver Disease with Cirrhosis
Nantawat Satthawiwat, Suthida Visedthorn, Pakorn Ruengket, Prangwalai Chanchaem, Pattida Kongsomboonchoke, Monravee Tumkosit, Pairoj Chattranukulchai, Sunchai Payungporn, Pisit Tangkijvanich
Published online January 27, 2026
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00507
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is an independent risk factor for cardiovascular disease (CVD). While gut bacteria have been linked to CVD, the [...] Read more.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an independent risk factor for cardiovascular disease (CVD). While gut bacteria have been linked to CVD, the role of intestinal fungi in subclinical coronary atherosclerosis (SCA) remains unclear. In this study, we aimed to investigate the association between the gut mycobiome and SCA in MASLD.

A cross-sectional study was conducted among 103 MASLD patients without established CVD. Fibrosis and steatosis were assessed using magnetic resonance elastography (MRE) and proton density fat fraction, respectively. SCA was defined by coronary artery calcification (CAC). Fecal fungal composition was analyzed via internal transcribed spacer sequencing.

Mean age was 60.8 ± 11.2 years; 51.5% were men; 20.4% had cirrhosis. CAC correlated with MRE (r = 0.489, p < 0.001), interleukin-6 (r = 0.407, p < 0.001), and tumor necrosis factor-α (r = 0.254, p = 0.018), but not proton density fat fraction. Cirrhosis patients had higher CAC than F0–F3 (456.9 vs. 205.9, p = 0.033). Candida albicans (C. albicans) abundance was greater in cirrhosis and correlated with CAC (r = 0.403, p < 0.001) and MRE (r = 0.212, p = 0.032). In multivariate analysis, older age, diabetes, obesity, cirrhosis, and enriched C. albicans independently predicted CAC ≥ 100 AU in MASLD.

In MASLD, cirrhosis and C. albicans enrichment are independently associated with higher SCA burden, suggesting advanced liver disease and a potential fungal contribution to CVD pathogenesis.

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Letter to the Editor Open Access
Acute Hepatitis E: A Global Problem, a European Vision
Javier Guinea-Castanares, Jesus Iturralde-Iriso, Irune Elizondo-Pinillos, Gloria Martinez-Iniesta
Published online August 27, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00331
Mini Review Open Access
Combination Strategies for Immunotherapy in Acute Myeloid Leukemia
Hongjun Guo, Yuan Bao, Shuai Feng, Tonghua Yang, Zengzheng Li
Published online March 28, 2026
Oncology Advances. doi:10.14218/OnA.2025.00032
Abstract
Despite the emergence of new approaches in acute myeloid leukemia (AML) treatment in recent years, the overall prognosis remains poor. Particularly for elderly patients and relapsed/refractory [...] Read more.

Despite the emergence of new approaches in acute myeloid leukemia (AML) treatment in recent years, the overall prognosis remains poor. Particularly for elderly patients and relapsed/refractory cases, the five-year survival rate consistently remains below 30%. While traditional chemotherapy regimens can rapidly suppress tumor burden and alleviate clinical symptoms, they suffer from limitations such as insufficient targeting, prominent toxic side effects, and a tendency to induce drug resistance. Immunotherapy offers a novel therapeutic pathway for AML due to its advantages of precise targeting, long-lasting antitumor effects, and a controllable safety profile. However, single-agent immunotherapy demonstrates limited clinical response rates in AML and struggles to achieve complete tumor cell clearance. In this context, combination regimens of chemotherapy and immunotherapy are increasingly becoming the focus of research. This review aims to summarize the rationale and advances in the combination of immune checkpoint inhibitors, chimeric antigen receptor T-cell therapy, antibody-drug conjugates, bispecific antibodies, and cancer vaccines with chemotherapy for the treatment of AML. We have detailed the preclinical research and clinical trial progress of each combined regimen, analyzed the core challenges—including off-target toxicity, high tumor heterogeneity, and limited efficacy in specific AML subtypes—and further propose targeted solutions and future development directions, such as exploring novel specific antigens, developing multi-targeted drugs, and formulating precision individualized treatment plans. The clinical application of such combined strategies is attracting increasing attention. In conclusion, chemo-immunotherapy combinations represent a highly promising therapeutic paradigm for AML, harnessing the synergy of chemotherapy-mediated immune microenvironment remodeling and the specific antitumor activity of immunotherapies to overcome single-agent limitations and deliver meaningful survival benefits.

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