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Original Article Open Access
Risheng He, Yi Xu, Pengbo Zhang, Liang Yu, Jian Ma, Yunfu Cui
Published online September 24, 2025
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00127
Abstract
Cell cycle checkpoint-related genes (CCCRGs) are implicated in the development and progression of hepatocellular carcinoma (HCC). However, their precise roles and underlying mechanisms [...] Read more.

Cell cycle checkpoint-related genes (CCCRGs) are implicated in the development and progression of hepatocellular carcinoma (HCC). However, their precise roles and underlying mechanisms remain insufficiently characterized and require further investigation. This study aimed to explore the prognostic significance of CCCRGs in HCC, and to investigate the mechanism by which they promote the progression of HCC.

HCC datasets from The Cancer Genome Atlas and International Cancer Genome Consortium were analyzed to identify hub genes. A prognostic model was constructed and validated using Kaplan–Meier analysis, nomogram, calibration curves, decision curve analysis, and receiver operating characteristic analysis. Immune infiltration patterns were assessed using single sample gene set enrichment analysis, while pathway activities were evaluated via gene set variation analysis. Single-cell RNA sequencing data from GSE149614 were analyzed with Seurat and CellChat to investigate cell–cell communication. Patient-derived HCC specimens were examined through immunohistological evaluation, HCC cell lines were used for in vitro functional assays, and in vivo tumor growth was assessed through animal experiments.

CCCRGs showed significant associations with prognosis, malignant biological behavior, and immune responses in HCC. Centromere protein (CENP) I was identified as a critical hub gene that markedly promoted HCC proliferation, metastasis, and epithelial–mesenchymal transition, while inhibiting apoptosis. Mechanistically, CENPI suppressed YAP phosphorylation, enhancing its nuclear translocation and thereby driving malignant progression. Additionally, CENPI impaired immune effector cell infiltration, likely by disrupting tumor antigen presentation and chemokine-mediated CD8+ T cell chemotaxis, thereby promoting immune escape.

This study underscores the prognostic significance of CCCRGs in HCC and identifies CENPI as a key driver of tumor progression through the Hippo pathway. Furthermore, it reveals CENPI’s role in promoting immune escape, suggesting novel therapeutic targets for HCC treatment.

Full article
Letter to the Editor Open Access
Fukui Zhang
Published online June 30, 2025
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00168
Research Letter Open Access
Chong Yang, Xinyu You, Donghui Cheng, Wenbin Cao, Tao Lu, Wenjun Jiang, Jipeng Jiang, Bangyou Zuo, Yu Zhang
Published online July 22, 2025
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00107
Original Article Open Access
Huiqing Liang, Xiaoting Zheng, Xiaowen Wu, Luyun Zhang, Yaoyu Liu Yanru Zheng, Manying Zhang, Min Hu, Min Jia, Yan Dai, Yizhi Xie, Shaodong Chen
Published online September 18, 2025
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Future Integrative Medicine. doi:10.14218/FIM.2025.00020
Abstract
Peginterferon-α treatment exhibits low rates of the serological conversion rate of hepatitis B e antigen (HBeAg) and the negative conversion rate of hepatitis B virus (HBV) DNA, [...] Read more.

Peginterferon-α treatment exhibits low rates of the serological conversion rate of hepatitis B e antigen (HBeAg) and the negative conversion rate of hepatitis B virus (HBV) DNA, with significant myelosuppression leading to treatment discontinuation in some patients. Traditional Chinese medicine (TCM) may ameliorate liver inflammation and modulate immune responses. This study aims to investigate the efficacy of combining TCM with pegylated-interferon (PEG-IFN) α-2b and its impact on myelosuppression adverse effects.

This study included 117 HBeAg-positive chronic hepatitis B (CHB) patients who started initial antiviral therapy at Xiamen Hospital of TCM between June 2018 and January 2023. According to the treatment regimen, patients were divided into the observation group (n = 56, receiving PEG-IFN α-2b combined with Licorice 15 g, Angelica sinensis 20 g, Poria 20 g, Paeonia lactiflora 20 g, Rhizoma Atractylodis Macrocephalae 20 g, Radix Bupleurum Chinense 20 g, Mentha piperita 3 g, Ginger three slices for more than six months) and the control group (n = 61, receiving PEG-IFN α-2b alone). This study retrospectively analyzed etiological indicators, liver biochemical indicators, and blood routine tests before and after treatment.

After 24 and 48 weeks of treatment, the observation group demonstrated significantly superior outcomes to the control group in quantitative reduction of hepatitis B surface antigen, the serological conversion rate of HBeAg, and the reduction in HBV DNA quantification (P < 0.05). By week 48, the HBV DNA negative conversion rate in the observation group (46.67%) was significantly higher than that in the control group (26.67%) (P < 0.05). Regarding safety, the incidence of myelosuppression in the observation group was significantly lower than that in the control group at both 24 and 48 weeks of treatment (P < 0.05)

Real-world findings demonstrate that adjunctive TCM significantly enhances the antiviral efficacy of peginterferon α-2b in HBeAg-positive CHB patients while concurrently mitigating treatment-limiting myelosuppression. This combination strategy may represent a clinically valuable approach to optimizing interferon-based therapy for CHB.

Full article
Study Protocol Open Access
Qingping Deng, Zilian Ye, Xiaotu Xi, Xing Zeng, Qing Liu, Rongyuan Yang
Published online October 23, 2025
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Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2025.00003
Abstract
COVID-19 has resulted in significant long-term sequelae in convalescent patients, impacting overall quality of life. Traditional Chinese medicine (TCM) has shown promise in managing [...] Read more.

COVID-19 has resulted in significant long-term sequelae in convalescent patients, impacting overall quality of life. Traditional Chinese medicine (TCM) has shown promise in managing post-COVID-19 symptoms through syndrome differentiation. This study aimed to evaluate the efficacy and safety of TCM in COVID-19 convalescent patients in a real-world setting.

This prospective, real-world study will be conducted at Guangdong Provincial Hospital of Traditional Chinese Medicine. A total of 528 COVID-19 convalescent patients will be recruited and divided into two groups: a control group receiving routine Western medical treatment and an intervention group receiving additional TCM treatment based on syndrome differentiation. Patients will be assessed for three major TCM syndromes: Lung-Spleen Qi Deficiency, Qi-Yin Deficiency, and Cold Phlegm Obstructing the Lung, with corresponding TCM prescriptions administered accordingly. The primary outcome measure will be the improvement in clinical symptom scores based on a TCM symptom scoring system. Secondary outcomes will include changes in laboratory tests, imaging studies, heart function classification, and quality of life scores. Safety will be assessed through liver and kidney function tests and adverse event monitoring.

The study is expected to demonstrate that TCM treatment, based on syndrome differentiation, can significantly improve clinical symptoms and overall health in COVID-19 convalescent patients compared to routine Western medical treatment. These findings will provide evidence for integrating TCM into post-acute COVID-19 care.

This study will contribute to the evidence supporting TCM as an effective treatment for post-COVID-19 syndrome, enhancing patient outcomes and informing comprehensive recovery strategies.

Full article
Original Article Open Access
Roa’a Haraka, Raghad Alghamdi, Orjwan Sami Mattar, Arwa Alharthi, Thekra Algasim, Sherooq Haraka, Mohammed Shammas, Muazzam Sheriff Maqbul
Published online November 4, 2025
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Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2025.00034
Abstract
Clove essential oil (CEO) derived from Syzygium aromaticum and miswak (Salvadora persica) contains bioactive compounds with antimicrobial properties. Due to the growing interest [...] Read more.

Clove essential oil (CEO) derived from Syzygium aromaticum and miswak (Salvadora persica) contains bioactive compounds with antimicrobial properties. Due to the growing interest in alternatives to conventional antibiotics, this study aimed to evaluate the in vitro antimicrobial efficacy of CEO, miswak, and their combination against key peri-implantitis pathogens.

The antimicrobial activities of CEO, miswak, and their combinations were tested against Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia. Disc diffusion and serial dilution methods were used to measure the inhibition zones and minimum inhibitory concentrations, respectively. Doxycycline served as a standard antibiotic for comparison, while ethanol was used as a negative control. Data were analyzed using one-way analysis of variance and Tukey’s honestly significant difference test, with significance set at α = 0.05.

CEO exhibited inhibition zones of 10–16 mm, comparable to that of doxycycline (13–16 mm), whereas miswak (6–13 mm vs. 1–14 mm) and the CEO–miswak combination (8–14 mm vs. 0–14 mm) showed lower activity. Mean minimum inhibitory concentration values were lowest for doxycycline (1.73 ± 0.46 µg/mL), followed by CEO (2.37 ± 0.24 µg/mL) and CEO–miswak combination (2.92 ± 0.12 µg/mL). Statistical analysis showed that the CEO–miswak combination was less effective than CEO (p = 0.0326) and doxycycline (p = 0.0001), but not different from miswak (p = 0.9836). CEO showed slightly greater activity than miswak (p = 0.0605).

Among the natural extracts tested, CEO exhibited superior antimicrobial efficacy, whereas miswak was less effective. The combination of CEO with miswak did not enhance antimicrobial efficacy, suggesting antagonistic interactions between their bioactive compounds.

Full article
Systematic Review Open Access
Jing Qiao, Junyan Gao, Xinxin Huang, Lun Gu, Yihang Song, Tongchang Wang, Zhaoshen Li, Zixuan He, Shuling Wang, Yu Bai
Published online December 25, 2025
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Cancer Screening and Prevention. doi:10.14218/CSP.2025.00021
Abstract
Terminal ileum intubation is considered the completion step of colonoscopy and is usually performed to assess the ileum. The histological examination of the ileal mucosa, which [...] Read more.

Terminal ileum intubation is considered the completion step of colonoscopy and is usually performed to assess the ileum. The histological examination of the ileal mucosa, which is acquired during terminal ileum intubation, may allow an accurate diagnosis. However, there is no absolute consensus on when ileoscopy and biopsy should be attempted. As a result, we aimed to evaluate whether terminal ileum intubation and biopsy should be performed routinely.

Systematic searches were performed in the PubMed, EMBASE, and Cochrane Library databases, as well as the Science Citation Index via the Web of Science platform. Reference lists from the identified papers were manually searched. Systematic searches were performed from January 1, 1971, to October 1, 2025. Studies reporting on terminal ileum intubation and biopsy during colonoscopy were included. Case reports, letters, reviews, and animal studies were excluded. The primary outcomes were the diagnostic yield of terminal ileum intubation and the rate of necessitating a change in management. Data were extracted independently by three reviewers.

Thirty-six studies were included. The subtotal diagnostic yield and the rate of necessary change among the selected patients were much greater than those among the unselected patients (5.1% versus 2.5% and 1.5% versus 0.4%, respectively). In addition, the diagnostic yield was found more frequently for inflammatory bowel disease, anemia, abdominal pain, and chronic diarrhea than for the other indications (26.7%, 16.1%, 14.9%, 12.4%, and 3.2%, respectively). The yield of ileal histopathology with a normal endoscopic appearance was low in both unselected and selected patients (3.5% and 2.4%, respectively).

Terminal ileum intubation is recommended as gold standard for completing colonoscopy. Biopsy should be considered in patients with abnormal endoscopic findings or specific high-risk symptoms.

Full article
Original Article Open Access
Swati Bhardwaj, Shenyu Wang, Yuxin Liu
Published online December 19, 2025
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Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2025.00013
Abstract
Endometrial polyp (EMP) is one of the most common diagnoses in the evaluation of women with abnormal uterine bleeding. Understanding the malignancy risk associated with EMPs and [...] Read more.

Endometrial polyp (EMP) is one of the most common diagnoses in the evaluation of women with abnormal uterine bleeding. Understanding the malignancy risk associated with EMPs and related risk factors is essential for guiding both pathology practice and clinical management. This study aimed to explore risk factors for malignancy in EMPs.

The pathology database was searched for women diagnosed with EMP between 2021 and 2022. Patient age, polyp size, background endometrium, recurrence, and (if applicable) cancer types were recorded. Immunohistochemistry (IHC) for p53 and p16 was performed on selected cases. Risk factors for malignancy were analyzed using Chi-square and analysis of variance tests.

Among the 740 EMP cases analyzed, 94% were benign, 2% were premalignant, and 4% were malignant. The median patient age was 54 years (range: 19–92). Minimal serous carcinoma (n = 14, 2%) was the most prevalent cancer. Among the 52 cases with p53 IHC, 38 were diagnosed as benign, supported by a wild-type p53 pattern, while 14 were diagnosed as serous carcinoma, supported by a mutant p53 pattern. Malignant polyps were found to be significantly associated with advanced age and malignant background endometrium (p < 0.001). Large size and recurrence were not identified as significant risk factors.

EMPs carry a low risk of malignancy, which is not significantly influenced by the polyp’s size or its recurrence. Our findings highlight the significantly elevated risk of malignancy in elderly patients and the importance of p53 IHC in improving diagnostic accuracy.

Full article
Original Article Open Access
O. Vishnevsky, K. Kuzminykh, I. Yatsyk, E. Kondratyuk, I. Chadaeva
Published online November 25, 2025
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Gene Expression. doi:10.14218/GE.2025.00050
Abstract
Empirical and theoretical studies can be distinguished among the areas of investigation of the renin-angiotensin-aldosterone system (RAAS) and its relationship with the development [...] Read more.

Empirical and theoretical studies can be distinguished among the areas of investigation of the renin-angiotensin-aldosterone system (RAAS) and its relationship with the development of cardiovascular diseases. Theoretical work is based mainly on the bioinformatic analysis of key elements of RAAS (genes, proteins, metabolites), on calculations and predictions of protein interactions, and on mechanisms of RAAS gene expression regulation. An associative gene network based on big data analysis allows us to reveal relationships among the proteins, regulatory pathways, and biological processes acting in RAAS, as well as to identify new diagnostic markers, therapeutic targets, putative molecular mechanisms of the development of RAAS-associated diseases, drug interactions, and drug toxicity.

The reconstruction and analysis of associative gene networks were performed using ANDSystem. The regulation of RAAS-associated gene expression was analyzed by transcription factor (TF) binding sites (TFBSs) prediction in the proximal promoters of these genes and by studying interactions between TFs themselves using the Ensembl Biomart web service and AnimalTFDB 4.0. The recognition of potential TFBSs in RAAS gene promoters was performed using MoLoTool.

According to the centrality criteria of the RAAS associative gene network, the following proteins were identified as exerting a significant influence on information interplay between network components: IL6, EDN1, TNFA, MK01, LEP, and JUN. Analysis of the ten identified TFs and their TFBSs among the genes in the RAAS network under study revealed clusters of three to 26 genes regulated by them.

Components with the highest values of centrality and vertex degrees were identified in the reconstructed associative gene network of the RAAS, and ten TFs supposed to regulate 26 RAAS genes were determined.

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Original Article Open Access
Telapolu Srivani, Mangathayaru Kalachaveedu, Sugin Lal Jabaris, Cordelia John
Published online June 28, 2025
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Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2025.00013
Abstract
MD-1 is a time-tested polyherbal diabetes supplement in Tamil Nadu, India. It is composed of dried powdered herbs: Phyllanthus amarus Schum. & Thonn, Tinospora cordifolia (Willd.) [...] Read more.

MD-1 is a time-tested polyherbal diabetes supplement in Tamil Nadu, India. It is composed of dried powdered herbs: Phyllanthus amarus Schum. & Thonn, Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms, Emblica officinalis Gaertn., Eugenia jambolana Lam., Gymnema sylvestre R. Br. Ex, and Cassia auriculata Linn. This study aimed to investigate the in vivo effects of MD-1 in high-fat diet (HFD)-induced diabetes mellitus in C57BL/6J mice.

After 10 weeks of HFD induction, diabetic mice (n = 60) were randomized to 21-day treatments with MD-1, metformin, or left untreated on a standard pellet diet. Fasting blood glucose, triacylglycerol (TAG), total cholesterol, and liver tissue markers including superoxide dismutase, glutathione peroxidase, glutathione, thiobarbituric acid reactive substance, glucokinase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase expressions were measured. Adipose tissue tumor necrosis factor (TNF)-α infiltration and messenger RNA expression of peroxisome proliferator-activated receptor γ (PPAR-γ) and glucose transporter type 4 (Glut4) were also analyzed.

MD-1 treatment significantly reduced elevated fasting blood glucose, TAG, and total cholesterol in HFD-fed mice and countered HFD-induced weight gain despite unchanged caloric intake. Improved adipose tissue function was evidenced by reduced TNF-α infiltration and increased messenger RNA expression of PPAR-γ and Glut4. MD-1 attenuated HFD-induced fatty liver disease by reducing oxidative stress and TAG accumulation, suggesting a possible two-hit mechanism.

MD-1 administration primarily targets adipose tissue TNF-α signaling in HFD mice, restoring function via PPAR-γ/Glut4 expression. These findings support its glycemic intervention potential and justify its supplementation in diabetes.

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