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Original Article Open Access
Prognostic Nutritional Index Predicts Outcomes in Hepatocellular Carcinoma Treated with Atezolizumab and Bevacizumab: A Propensity Score-matched Analysis
Yuan-Hung Kuo, Wei Teng, Yen-Hao Chen, Po-Ting Lin, Tsung-Han Wu, Chung-Wei Su, Wei-Ting Chen, Chen-Chun Lin, Chao-Hung Hung, Sheng-Nan Lu, Shi-Ming Lin, Jing-Houng Wang, Chun-Yen Lin
Published online December 8, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00418
Abstract
The prognostic nutritional index (PNI), calculated from serum albumin and lymphocyte count, reflects a patient’s immune-nutritional status and has been proposed as a prognostic [...] Read more.

The prognostic nutritional index (PNI), calculated from serum albumin and lymphocyte count, reflects a patient’s immune-nutritional status and has been proposed as a prognostic marker in hepatocellular carcinoma (HCC). However, its role in advanced HCC patients treated with atezolizumab plus bevacizumab (Ate/Bev) remains unclear. In this study, we aimed to evaluate the prognostic value of PNI in patients receiving first-line Ate/Bev therapy.

We retrospectively analyzed 362 patients with unresectable HCC who received Ate/Bev between November 2020 and June 2023 across two centers. Based on prior literature, a cutoff of 45 was used to classify patients into low-PNI (<45) and high-PNI (≥45) groups. Propensity score matching was performed to balance baseline characteristics.

After propensity score matching, 130 patients (65 per group) were included in the analysis. The high-PNI group showed a significantly lower incidence of grade ≥ 3 treatment-related adverse events (10.8% vs. 24.6%, p = 0.039), a higher objective response rate (38.4% vs. 20.0%, p = 0.037), and significantly longer overall survival (16.7 vs. 7.9 months, p = 0.009). Although progression-free survival was longer in the high-PNI group (4.8 vs. 3.0 months), the difference was not statistically significant (p = 0.597). Multivariate analysis confirmed that PNI was an independent predictor of overall survival (hazard ratio: 0.574, 95% confidence interval: 0.353–0.933, p = 0.025), after adjusting for vascular invasion, alpha-fetoprotein levels, concurrent therapy, and post-treatment interventions.

PNI is an independent prognostic factor for overall survival in advanced HCC patients treated with Ate/Bev in real-world clinical practice. Incorporating PNI into routine assessments may enhance risk stratification and guide therapeutic decision-making.

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Editorial Open Access
Editorial Open Access
Beyond the Endoscope: The Promise of Blood-based Biomarkers for Gastric Mucosal Changes
Jia Shen, Lihua Ren, Hong Chen
Published online September 30, 2025
Cancer Screening and Prevention. doi:10.14218/CSP.2025.00020
Original Article Open Access
TF-rs1049296 C>T Variant Modifies the Association between Hepatic Iron Stores and Liver Fibrosis in Metabolic Dysfunction-associated Steatotic Liver Disease
Sui-Dan Chen, Ka-Te Huang, Huai Zhang, Yang-Yang Li, Yi Jin, Hai-Yang Yuan, Pei-Wu Zhu, Jian-Min Li, Christopher D. Byrne, Giovanni Targher, Ming-Hua Zheng
Published online December 11, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00305
Abstract
Hepatic iron deposition (HID) in the reticuloendothelial system (RES) is associated with histological severity in metabolic dysfunction-associated steatotic liver disease (MASLD). [...] Read more.

Hepatic iron deposition (HID) in the reticuloendothelial system (RES) is associated with histological severity in metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to assess the interaction between the transferrin (TF)-rs1049296 C>T variant and HID patterns on the risk of significant liver fibrosis in MASLD.

We analyzed 406 adults with liver biopsy-confirmed MASLD. HID was categorized as hepatocellular, RES, or mixed, based on Perl's iron staining. The association between iron-related genetic variants and significant liver fibrosis (fibrosis stage ≥ F2) was analyzed, focusing on the interactions between single-nucleotide polymorphism genotypes and iron deposition patterns. Multivariable logistic regression analysis was used to adjust for potential confounders.

HID was detected in 271 (66.7%) patients, with hepatocellular, RES, and mixed patterns accounting for 11.1%, 18.0%, and 37.7%, respectively. A significant interaction was observed between HID and the TF-rs1049296 genotype (P = 0.035 for interaction). In multivariable analysis, male sex, hypertension, severe lobular inflammation, and mixed hepatocellular/RES iron deposition were independent predictors of significant liver fibrosis. RES deposition markedly increased the risk of significant liver fibrosis (adjusted odds ratio: 6.65; 95% confidence interval: 1.84–23.97, p < 0.05), particularly in men with isolated RES iron deposition (adjusted odds ratio: 5.26; 95% confidence interval: 1.21–22.81, p < 0.05).

The TF-rs1049296 T allele interacts with RES iron deposition to identify a MASLD subpopulation at elevated risk of progressive liver disease, providing opportunities for refined risk stratification and personalized management.

Full article
Original Article Open Access
Long-term Results of Initial Gamma Knife Radiosurgery for Acromegaly: A Retrospective Cohort Study
Jiaming Fu, Zijing Wang, Yanli Li, Yinhui Deng, Junyi Fu, Jinxiu Yu
Published online December 25, 2025
Neurosurgical Subspecialties. doi:10.14218/NSSS.2025.00034
Abstract
Acromegaly requires multimodal management. While surgery is first-line, many patients have persistent/recurrent disease. Gamma knife radiosurgery (GKRS) offers precise radiation, [...] Read more.

Acromegaly requires multimodal management. While surgery is first-line, many patients have persistent/recurrent disease. Gamma knife radiosurgery (GKRS) offers precise radiation, but data on its use as initial therapy remain limited. This study aimed to review the outcomes and report on our experience in treating patients with acromegaly using initial GKRS.

We retrospectively identified 33 patients with acromegaly who underwent GKRS from 1993 until 2016 at the Department of Radiotherapy, the Second Affiliated Hospital of Guangzhou Medical University. These patients had complete endocrine, radiological, and imaging data before and after GKRS. Furthermore, univariate and multivariate analysis was utilized to analyze the potential prognostic factors of endocrine remission and new-onset hypopituitarism.

Thirty-three patients were enrolled in the study. Fifteen patients (45.5%) were males and 18 (54.5%) were females. The median age was 44.0 years (range, 24.9–66.2 years). During a median follow-up of 65.6 months (range, 12.9–297.6), the median margin dose for GKRS was 15.0 Gy (range, 10.8–20.3 Gy). Endocrine remission was achieved in nine of the 33 patients (27.3%) over a mean follow-up of 85.1 months (range, 12.9–161.3). No prognostic factors demonstrated a significant association with endocrine remission. New-onset hypopituitarism occurred in eight patients (24.2%) after GKRS. The tumor control rate was 100%. Only one patient developed worsening visual dysfunction. No new cranial neuropathy was noted.

Initial GKRS for acromegaly provided effective tumor control and partial endocrine remission with a favorable safety profile, notably a low rate of new-onset hypopituitarism, representing a viable treatment option.

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Review Article Open Access
Primary Biliary Cholangitis–associated Osteoporosis: Contemporary Review of Pathogenesis and Management
Jiaqi Yang, Shuhao Su, Ting Yuan, Caiyun Yang, Jie Luo, Xingchen Liu, Guanya Guo, Changcun Guo, Ying Han
Published online January 14, 2026
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00505
Abstract
Primary biliary cholangitis (PBC) is a chronic cholestatic disorder in which symptoms exert a direct influence on patients’ quality of life. Beyond pruritus and fatigue, patients [...] Read more.

Primary biliary cholangitis (PBC) is a chronic cholestatic disorder in which symptoms exert a direct influence on patients’ quality of life. Beyond pruritus and fatigue, patients with PBC are also prone to developing osteoporosis (OP). This skeletal condition not only heightens the likelihood of fractures but is also associated with elevated mortality. With the overall prevalence of PBC rising, a parallel increase in OP incidence among these patients can be anticipated. Early recognition, preventive strategies, and appropriate therapeutic approaches are essential for preserving patients’ quality of life. Nevertheless, current data on the management of OP in PBC remain limited. Most existing recommendations are extrapolated from studies on postmenopausal OP. However, these findings have not been effectively adapted into practical management protocols for PBC-related OP, largely due to distinct pathophysiological mechanisms between the two conditions. The absence of well-established preventive and therapeutic measures continues to represent a major obstacle in addressing OP among patients with PBC. This review offers a detailed synthesis of the epidemiology, underlying mechanisms, and therapeutic considerations of OP linked to PBC.

Full article
Original Article Open Access
Protection against Endothelial Injury Mediates the Anti-thrombotic Effect of Danggui Buxue Decoction in a Rat Model of Cirrhotic Portal Vein Thrombosis
Yanan Guo, Sisi Dong, Meng Li, Yanyan Tao, Jing Lv, Chenghai Liu
Published online December 5, 2025
Gastroenterology & Hepatology Research. doi:10.14218/GHR.2025.00001
Abstract
PVT is a harmful event in cirrhosis, and the prevention and treatment of PVT are important in the management of cirrhosis and portal hypertension. The study aimed to observe the [...] Read more.

PVT is a harmful event in cirrhosis, and the prevention and treatment of PVT are important in the management of cirrhosis and portal hypertension. The study aimed to observe the efficacy of Danggui Buxue Decoction (DBD) on portal vein thrombosis (PVT) in cirrhosis and to elucidate the related mechanism using a modified animal model.

A model of PVT in cirrhosis was established by partial portal vein ligation and intraperitoneal injection of CCl4 in rats, which showed obvious PVT with intra- and extravenous thrombosis as well as liver cirrhosis. Rats were randomly assigned into four groups and received intragastric administration of DBD (12 g/kg/day) or rivaroxaban (20 mg/kg/day) for 6 weeks.

DBD attenuated collagen deposition and reduced thrombus formation in model livers, increased portal vein blood flow, expanded the portal vein diameter, and reduced prothrombin time and international normalized ratio in the model rats. In addition, DBD reduced hepatic von Willebrand factor and plasminogen activator inhibitor-1 expression and increased hepatic fibrin degradation product content in the liver tissues of model rats.

We modified a model of cirrhotic PVT in rats and found that DBD had a good effect on PVT and liver fibrosis, with the mechanisms related to the enhancement of portal vein blood flow and the protection against endothelial cell injury.

Full article
Original Article Open Access
SERF2 (Hero7) Gene Polymorphism is Associated with Severe Course of COVID-19
Anna Dorofeeva, Maxim Ivenkov, Ksenia Kobzeva, Olga Bushueva
Published online October 30, 2025
Gene Expression. doi:10.14218/GE.2025.00057
Abstract
Chaperone-like proteins are involved in the pathogenesis of coronavirus infection through regulation of the viral life cycle, immune response, and antigen presentation. A recently [...] Read more.

Chaperone-like proteins are involved in the pathogenesis of coronavirus infection through regulation of the viral life cycle, immune response, and antigen presentation. A recently discovered class of chaperones, called heat-resistant obscure proteins (Hero proteins), performs functions similar to other molecular chaperones. This study aimed to investigate the association between the gene encoding the Hero protein SERF2 (Hero7) and the risk of severe COVID-19.

This case-control study was conducted according to the STROBE protocol. A total of 1,373 unrelated Russians (178 patients with severe COVID-19 and 1,195 controls) were recruited. Genotyping of rs4644832 in the SERF2 gene was performed using a probe-based polymerase chain reaction approach. The effects of the single nucleotide polymorphisms (SNPs) were analyzed using bioinformatics tools, including GTExPortal, eQTLGen, HaploReg, atSNP, Gene Ontology, Lung Disease and Common Metabolic Diseases Knowledge Portals, and the STRING database.

SNP rs4644832 in the SERF2 gene (effect allele G) was associated with a decreased risk of severe COVID-19 in the total sample (odds ratio (OR) = 0.56, 95% confidence interval (CI) 0.39–0.81, P = 0.001), females (OR = 0.51, 95% CI 0.31–0.87, P = 0.006), non-smokers (OR = 0.46, 95% CI 0.29–0.74, P = 0.0004), individuals with body mass index ≥ 25 (OR = 0.42, 95% CI 0.25–0.7, P = 0.0004), individuals with low fruit and vegetable intake (OR = 0.38, 95% CI 0.22–0.67, P = 0.0004), and individuals with low physical activity (OR = 0.41, 95% CI 0.23–0.75, P = 0.002).

The G allele of rs4644832 in the SERF2 gene appears to have a protective effect against severe COVID-19. Functional annotation of rs4644832 suggests that it may influence COVID-19 pathogenesis through regulation of proteostasis, ubiquitination, inflammation-induced protein aggregation, the viral life cycle, and cytoskeletal functions.

Full article
Review Article Open Access
Traditional Chinese Medicine in Febrile Neutropenia Treatment: Advances and Prospects
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
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.

Full article
Original Article Open Access
Serum Interleukin-8 for Differentiating Invasive Pulmonary Aspergillosis from Bacterial Pneumonia in Patients with HBV-Associated Acute-on-Chronic Liver Failure
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
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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