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Original Article Open Access
Lanyue Huang, Yuzhao Feng, Wei Wang, Wei Liu, Yunhui Liu, Liang Chen, Yuxin Niu, Tingting Liu, Mi Song, Yiwei Xu, Zhongyuan Yang, Guang Chen, Qin Ning, Tao Chen, Lin Zhu
Published online December 26, 2025
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00645
Abstract
Infections are frequent and lethal complications of acute-on-chronic liver failure (ACLF). Reliable biomarkers to distinguish fungal from bacterial infections remain limited. Given [...] Read more.

Infections are frequent and lethal complications of acute-on-chronic liver failure (ACLF). Reliable biomarkers to distinguish fungal from bacterial infections remain limited. Given the central role of immune dysfunction in ACLF, we aimed to evaluate the diagnostic value of serum cytokines in differentiating invasive pulmonary aspergillosis (IPA) from bacterial pneumonia (BP) in HBV-associated ACLF.

This retrospective case-control study enrolled ACLF patients admitted to the Tongji Hospital, between 2018 and 2022. Patients were categorized into IPA, BP, and non-infection groups. The BP and non-infection groups were propensity score-matched to the IPA cases. Serum cytokines levels (IL-1β, sIL-2R, IL-6, IL-8, IL-10, TNF-α) and clinical data were collected, with the diagnostic performance of these cytokines as biomarkers assessed via ROC curves.

A total of 32 IPA, 96 BP, and 96 non-infection patients were enrolled, with balanced baseline characteristics. Compared with the non-infection group, the IPA group had higher sIL-2R (1,606.00 vs. 1,211.50 U/mL, P = 0.019) and IL-6 (69.03 vs. 15.98 pg/mL, P < 0.001) levels, but lower IL-8 levels (62.20 vs. 132.00 pg/mL, P = 0.025). The BP group showed elevated sIL-2R (1,792.00 U/mL), IL-6 (49.42 pg/mL), IL-10 (13.40 pg/mL) levels compared to the non-infection group (all P < 0.001). Also, IL-8 was lower in the IPA group than in the BP group (62.20 vs. 176.00 pg/mL, P < 0.001) and its assessment could best distinguish IPA from BP (AUC = 0.743, cut-off = 76.60 pg/mL; sensitivity = 66.7%, specificity = 82.1%).

Serum IL-8 exhibited superior diagnostic value for IPA in patients with HBV-ACLF and could effectively discriminate Aspergillus infections from bacterial infections.

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Review Article Open Access
Zaoqin Yu, Yanjiao Xu, Wei Li, Yingjie Hu, Chengliang Zhang
Published online January 23, 2026
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00622
Abstract
In the past decade, immune checkpoint inhibitors (ICIs) have dramatically changed cancer treatment, significantly improving outcomes for patients with various malignancies. Nonetheless, [...] Read more.

In the past decade, immune checkpoint inhibitors (ICIs) have dramatically changed cancer treatment, significantly improving outcomes for patients with various malignancies. Nonetheless, their widespread application has resulted in a rise in immune-related adverse events due to excessive immune activation, including immune-mediated hepatotoxicity (IMH). IMH can cause serious complications and even death, underscoring the need for early prediction and intervention. This review outlines the current understanding of risk factors and predictive biomarkers for IMH in cancer patients undergoing ICI therapy, with risk factors divided into patient-associated, tumor-associated, and agent-associated categories. Higher IMH risk is related to female sex, younger age, extreme BMI, Asian ethnicity, and chronic liver disease. Cancer type, prior ICI treatment, dual ICI combination therapy, and the concurrent use of chemotherapy, targeted agents, or other hepatotoxic drugs (e.g., acetaminophen, statins) also increase the risk of IMH. Potential predictive biomarkers encompass circulating blood cells, serum proteins, autoantibodies, cytokines, gene profiles, and the gut microbiome. Despite promising findings, the predictive value of these biomarkers remains inconsistent, and no definitive biomarker has been established for routine clinical use. Large-scale prospective studies are essential to verify the predictive value of these biomarkers and facilitate their integration into clinical practice, thereby providing deeper insights into the early identification and individualized management of IMH during ICI therapy.

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Review Article Open Access
Bin Niu, Jun Xu, Liaoyun Zhang
Published online January 19, 2026
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00401
Abstract
Primary hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide, with curative options still limited for patients with advanced disease. [...] Read more.

Primary hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide, with curative options still limited for patients with advanced disease. As an emerging modality of cancer immunotherapy, tumor vaccines represent a promising approach that activates the host immune system to recognize and eliminate malignant cells. Multiple vaccine platforms, including peptide vaccines, dendritic-cell vaccines, nucleic-acid vaccines, and viral-vector vaccines, have been explored for HCC. Among these, peptide- and dendritic-cell-based vaccines are supported by the most extensive clinical data, demonstrating favorable safety and immunogenicity profiles. The advent of personalized therapeutic cancer vaccines based on tumor-specific antigens has further refined the precision of vaccine design. Nevertheless, several major challenges persist, including immune suppression within the tumor immune microenvironment, marked tumor heterogeneity, immune-escape mechanisms, and limited vaccine immunogenicity, all of which hinder clinical efficacy. In addition, issues related to standardization, large-scale production, and regulatory oversight remain unresolved. Recent advances in sequencing technology, nanotechnology, and artificial intelligence have opened new avenues for optimizing vaccine platforms and delivery strategies. Combination therapies that integrate cancer vaccines with immune checkpoint inhibitors, chemotherapy, or locoregional treatments are also being actively investigated to improve patient outcomes. In summary, although vaccine-based immunotherapy for HCC is still at an early stage, its integration with personalized medicine and multimodal therapeutic strategies holds great potential for improving the long-term prognosis of patients with HCC. Therefore, this review aims to systematically summarize current advances in tumor vaccine–based immunotherapy for hepatocellular carcinoma, with a particular focus on vaccine platforms, target antigens, clinical trial outcomes, and future challenges for clinical translation.

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Original Article Open Access
Yeyu Song, Yameng Liu, Jie Jiang, Youjie Zheng, Zixuan Wang, Cen Xie, Jian-Gao Fan
Published online January 7, 2026
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00538
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) and sarcopenia frequently coexist, yet their causal relationship and underlying mechanisms remain poorly defined. [...] Read more.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and sarcopenia frequently coexist, yet their causal relationship and underlying mechanisms remain poorly defined. This study aimed to investigate whether a bidirectional causal link exists between MASLD and sarcopenia and to identify the molecular mediators involved in liver-muscle crosstalk.

We applied Mendelian randomization to test the causal effect of sarcopenia-related traits on MASLD risk. To capture distinct clinical features, we established complementary mouse models, including diet-induced and genetic (ob/ob) MASLD models, a stelic animal model, and a drug-induced muscle atrophy model. Multi-tissue transcriptomic profiling was performed on liver and muscle to uncover altered pathways.

Complementing prior genetic evidence establishing MASLD as a causal factor for sarcopenia, our Mendelian randomization analysis revealed that diminished muscle mass and muscle function contribute to an elevated risk of MASLD. In mice with MASLD, we observed loss of muscle mass, reduced strength, and ectopic lipid deposition in skeletal muscle. Conversely, muscle atrophy exacerbated hepatic steatosis, inflammation, and fibrosis in MASLD mice. Transcriptional profiling revealed that sarcopenia impairs hepatic metabolic homeostasis by enhancing fatty acid uptake and impairing oxidative phosphorylation, while MASLD, in turn, promotes muscle dysfunction by exacerbating inflammatory responses and metabolic dysfunction. We further identified C-C motif chemokine ligand 2 as a key myokine that drives MASLD, and adrenomedullin as a key hepatokine that triggers sarcopenia.

Our findings suggest a potential bidirectional causal relationship between MASLD and sarcopenia, which may be partially mediated by C-C motif chemokine ligand 2 and adrenomedullin.

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Original Article Open Access
Yue-Yang Ma, Wei-Hao Zhao, Ke-Ying Ou, Jia-Nan Cui, Chuan-Su Yuan, Bin Liu, Yong-Feng Yang, Qing-Fang Xiong
Published online January 15, 2026
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00424
Abstract
Autoimmune hepatitis (AIH) frequently coexists with extrahepatic autoimmune diseases (EADs), but their prevalence, characteristics, progression, and treatment effect in the Han [...] Read more.

Autoimmune hepatitis (AIH) frequently coexists with extrahepatic autoimmune diseases (EADs), but their prevalence, characteristics, progression, and treatment effect in the Han Chinese population remain unclear. This study aimed to evaluate the prevalence and spectrum of EADs and to assess their clinical features, disease course, and treatment outcomes in Han Chinese patients with AIH.

Medical records of 371 Han Chinese patients with AIH (diagnosed from March 2016 to October 2023) were retrospectively analyzed.

Among the 371 AIH patients, 304 (81.94%) were female, with a median age of 52.5 years (interquartile range, 46.0–61.0). A total of 23.98% (89/371) had at least one EAD, including 27.06% (82/303) in type 1 AIH, 11.11% (7/63) in antibody-negative AIH, and none in type 2. A single EAD was the most common (20.21%, 75/371). The most frequent EADs were Sjogren’s syndrome (8.63%) and autoimmune thyroid disease (8.36%). Compared with patients without EADs, those with EADs had lower alanine aminotransferase, red blood cell, and hemoglobin levels, but higher aspartate aminotransferase/alanine aminotransferase ratio and antinuclear antibody (ANA) positivity (all P < 0.05). ANA positivity was independently associated with EADs (odds ratio = 2.209, 95% confidence interval = 1.242–3.927, P = 0.007). After three months of treatment, the complete biochemical response rate was lower in the EADs group than in the non-EADs group (40.0% vs. 55.3%, P = 0.024), whereas no significant differences were observed at 6, 12, 24, or 36 months (all P > 0.05).

In the Han Chinese population, 23.98% of AIH patients had EADs, with Sjogren’s syndrome and autoimmune thyroid disease being the most common. ANA positivity was a significant risk factor for EADs. EAD patients had a poorer initial treatment response at three months, but comparable long-term biochemical response from six months.

Full article
Original Article Open Access
Ziyu Chen, Huiying Li, Shaobing Zhan, Xiaoguang Zhang, Hong Yu, Shuying Li
Published online December 30, 2025
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Oncology Advances. doi:10.14218/OnA.2025.00025
Abstract
Human papillomavirus (HPV) is a double-stranded circular DNA virus with a genome of approximately 7–8 kb. This study aimed to establish an overlapping extension polymerase chain [...] Read more.

Human papillomavirus (HPV) is a double-stranded circular DNA virus with a genome of approximately 7–8 kb. This study aimed to establish an overlapping extension polymerase chain reaction method for the amplification of the entire genome of HPV16.

The HPV16 genome was divided into two larger fragments (with lengths of 3.9 kilobases and 5.3 kilobases, respectively), each of which had overlapping regions of more than 500 base pairs. A nested primer (outer primer: Fout/Rout; inner primer: Fin/Rin) was used to amplify each fragment. The key reaction parameters were optimized, including the selection of two highly accurate DNA polymerases; and a series of diluted samples (initial concentration of 2,000 copies/microliter, diluted to 2, 20, 200, and 2,000 copies/microliter) were used for amplification tests to evaluate the sensitivity of this method.

This study demonstrated high sensitivity for HPV16 detection, with effective amplification of samples as low as 2 copies/µL. For low-concentration samples (<200 copies/µL), the Thermo Fisher enzyme showed 50% and 75% effective amplification success rates at 2 copies/µL and 20 copies/µL, respectively, while the Vazyme enzyme achieved 0% success at both concentrations. Both enzymes enabled stable amplification of high-concentration samples (≥200 copies/µL). The amplified products matched the theoretical size, and Illumina sequencing confirmed Q30 ≥ 96% and >98% identity with the HPV16 reference sequence (K02718.1).

This study provides a highly sensitive and specific method for the full-genome sequence analysis of HPV16, which is applicable to HPV16 full-genome sequencing, variation analysis, and other research.

Full article
Corrigendum Open Access
Magd A. Kotb, Enas Abd El Satar, Ahmed M. Badr, Nazira A. Abdalla, Iman A. Abdelaziz
Published online June 6, 2025
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Gene Expression. doi:10.14218/GE.2025.00008C
Review Article Open Access
Kangdi Cao, Jinkun Wang, Jiawei Wang, Shuo Wang, Dandan Wang, Shuaihang Hu, Bingjie Fan, Lanxin Zhang, Wei Hou, Xueqian Wang
Published online December 30, 2025
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Future Integrative Medicine. doi:10.14218/FIM.2025.00035
Abstract
Febrile neutropenia (FN) is one of the acute and serious complications of chemotherapy-induced myelosuppression in tumor patients. Antibiotics and granulocyte colony-stimulating [...] Read more.

Febrile neutropenia (FN) is one of the acute and serious complications of chemotherapy-induced myelosuppression in tumor patients. Antibiotics and granulocyte colony-stimulating factor are the mainstays of its treatment. However, this therapy still faces many challenges and may trigger drug resistance, as well as adverse effects such as bone pain and vasculitis. How to minimize treatment-related toxicity while ensuring therapeutic efficacy has become a key issue to be addressed in current clinical practice. In recent years, traditional Chinese medicine (TCM) has demonstrated unique advantages in the prevention and treatment of FN. We conducted a comprehensive search of the PubMed, Web of Science, and CNKI databases using keywords such as TCM and FN, covering the period from their establishment to May 2025. Clinical studies have shown that the combination of TCM and modern medicine can significantly reduce the incidence of FN, while also enhancing the number of granulocytes, shortening the duration of fever, improving the quality of life of patients, and reducing other toxic effects of chemotherapy. These results suggest that TCM is a promising and safe complementary therapy. However, more high-quality trials are needed to verify its benefits. This review summarizes the latest progress in the treatment of FN with TCM and discusses future development directions.

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Short Communication Open Access
W.J.A. Banukie N. Jayasuriya, L.D.A. Menuka Arawwawala, N.T. Bhavantha Dias, K. Pararamasingam, N.M.M. Fazlan, K.A. Samarasinghe, T. Sugandhika Suresh
Published online November 28, 2025
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Future Integrative Medicine. doi:10.14218/FIM.2025.00029
Abstract
Alpinia calcarata (A. calcarata) Roscoe (Family: Zingiberaceae) is a rhizomatous perennial herb used in traditional medicine to treat inflammatory conditions. This study aimed to [...] Read more.

Alpinia calcarata (A. calcarata) Roscoe (Family: Zingiberaceae) is a rhizomatous perennial herb used in traditional medicine to treat inflammatory conditions. This study aimed to develop a topical emulgel dosage form by incorporating the essential oil of A. calcarata rhizome and to investigate it’s in vitro anti-inflammatory activity. A thin-layer chromatographic fingerprint of the essential oil of A. calcarata rhizome was developed. Then, an emulsion base containing plant oil was formulated and incorporated within a Carbopol gel base. The physical characteristics of this formulation were evaluated subsequently. The anti-inflammatory mechanism of the emulgel was determined by in vitro blood cell membrane stabilization assay and thrombolytic activity assay. The results were statistically analyzed by one-way analysis of variance. The thin-layer chromatographic fingerprint of the test oil demonstrated several bands with unique retention factor values. The formulated herbal emulgel was white, viscous, and homogeneous in appearance. The spreadability was 118 g·cm/M, and the pH of the emulgel was 6.30 at 25°C. The A. calcarata emulgel significantly (p < 0.05) inhibited heat-induced in vitro hemolysis, with the highest activity at a 50 µg/mL dose (87.68 ± 0.35%) compared to the placebo. Furthermore, this activity was found to be dependent on the essential oil concentration (r2 = 0.99) of the emulgel. Therefore, it was concluded that the essential oil of A. calcarata rhizome is an effective active ingredient to be used in a topical emulgel formulation, whereas the diverse phytochemicals present in the essential oil would be the underlying source of its anti-inflammatory activity.

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Review Article Open Access
Mohammad Reza Kasaai
Published online January 30, 2026
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Cancer Screening and Prevention. doi:10.14218/CSP.2025.00022
Abstract
Breast cancer (BCA) is one of the most common cancers worldwide, with a high rate of incidence and mortality. This review provides global information on BCA therapy using curcumin. [...] Read more.

Breast cancer (BCA) is one of the most common cancers worldwide, with a high rate of incidence and mortality. This review provides global information on BCA therapy using curcumin. Chemotherapy, as an effective treatment for different stages of BCA, and curcumin, generally regarded as safe compound and an alternative to synthetic drugs, have been described for the treatment of BCA. A few parameters, including nano-curcumin versus bulk curcumin and its encapsulated form versus its corresponding free form, have been discussed. Curcumin, a safe and edible compound with antitumor properties, is a promising medicinal compound for the treatment of BCA. Encapsulation of curcumin enhances its stability and anticancer efficiency. Nano-curcumin exhibits superior properties when compared to its bulk counterparts, leading to notable interactions and effects.

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