Review Article
Open Access
Hepatic Stellate Cell Heterogeneity in Chronic Liver Fibrosis: Functional States and Translational Opportunities
Rui Chen, Yufei Yang, Guangwen Chen, Xiaobo Cai, Lungen Lu, Qichao Ge
Published online September 30, 2026
Journal of Translational Gastroenterology.
doi:10.14218/JTG.2026.00026
Abstract
Hepatic stellate cell (HSC) activation has traditionally been described as a binary transition from vitamin A-rich quiescent cells to alpha-smooth muscle actin-positive, collagen-producing
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Hepatic stellate cell (HSC) activation has traditionally been described as a binary transition from vitamin A-rich quiescent cells to alpha-smooth muscle actin-positive, collagen-producing myofibroblast-like cells. Advances in single-cell RNA sequencing, single-nucleus RNA sequencing, spatial transcriptomics, and chromatin-accessibility profiling now reveal a more complex and dynamic landscape. During chronic liver injury, HSCs can adopt five overlapping activation-associated states characterized by injury sensing, inflammatory signaling, proliferation, extracellular matrix production and contractility, together with a senescent state that represents a possible fate of activated HSCs. These states differ in their molecular markers, spatial distribution, regulatory pathways, and interactions with hepatocytes, liver sinusoidal endothelial cells, macrophages, natural killer cells, and cholangiocytes. Importantly, they are not fixed lineages and may coexist or interconvert during fibrosis progression and regression. This review revisits the classical quiescent-activated framework and proposes a state-based approach for interpreting HSC heterogeneity. We summarize the defining features and translational relevance of six major HSC functional states, discuss their multicellular niches, and highlight the opportunities and limitations of function-selective therapeutic targeting. A reproducible classification that integrates molecular identity, spatial context, and causal function may help refine antifibrotic treatment strategies.
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Original Article
Open Access
Comparison of Survival Between Patients with Hepatocellular Carcinoma Beyond the “Up-to-7” Criterion Who Received Adjuvant PD-1 Inhibitors or Active Surveillance: A Target Trial Emulation Study
Jia-Yong Su, Zhen Liu, Tai-Xin Yang, Ping-Ping Guo, Min Luo, Shao-Ping Liu, Xiao-Feng Dong, Xiao-Ling Xu, Shu-Chang Chen, Jun-Jie Ou, Kang Chen, Zhi-Cheng Li, Ze Su, Fu-Quan Yang, Wen-Hai He, Ning Peng, Pei-Sheng Wu, Bei-Bei Long, Hang Su, Mei-Lan Huang, Wen-Ting Li, Wen-Ting Chen, Jian-Rong Li, Da-Long Yang, Zhi-Hao Huang, Lei-Po Lin, Rong-Rui Huo, Yi-Li Ma, Liang Ma, Xiao-Bin Zhong, Jian-Hong Zhong, on behalf of the GUIDANCE investigators
Published online September 24, 2026
Journal of Clinical and Translational Hepatology.
doi:10.14218/JCTH.2026.00283
Abstract
The IMbrave050 trial suggested that adjuvant immune checkpoint inhibitor therapy may benefit patients with hepatocellular carcinoma exceeding the “up-to-7” criterion. This study
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The IMbrave050 trial suggested that adjuvant immune checkpoint inhibitor therapy may benefit patients with hepatocellular carcinoma exceeding the “up-to-7” criterion. This study aimed to compare survival outcomes and safety between such patients receiving adjuvant programmed cell death protein 1 inhibitors and those undergoing active surveillance after curative resection.
Data were prospectively collected from patients at 13 medical centers in China between 2019 and 2024. The study was designed according to a target trial emulation framework, and propensity score matching was used to reduce confounding. The primary endpoint was recurrence-free survival; secondary endpoints included overall survival and incidence of treatment-related adverse events.
Median follow-up was 32.7 months (interquartile range, 20.9–47.5). Propensity score matching yielded 200 patients per group. Median recurrence-free survival was longer in the adjuvant group (28.0 months; 95% confidence interval [CI], 21.7–34.3) than in the surveillance group (14.4 months; 95% CI, 10.7–18.1; hazard ratio, 0.58; 95% CI, 0.45–0.74). Median overall survival was not reached in the adjuvant group and was 45.0 months (95% CI, 37.8–52.1) in the surveillance group (hazard ratio, 0.63; 95% CI, 0.45–0.89). The most frequent grade 3–4 treatment-related adverse events were hand–foot skin reaction (7.2%), elevated alanine aminotransferase (5.8%), and elevated aspartate aminotransferase (5.3%).
Adjuvant programmed cell death protein 1 inhibitors, with or without molecularly targeted agents, were associated with longer recurrence-free survival and acceptable safety in patients with hepatocellular carcinoma exceeding the “up-to-7” criterion.
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Original Article
Open Access
Entecavir plus Fuzheng Huayu Compound Reduces the Risk of Portal Hypertension-related Complications in Patients with Compensated Hepatitis B Virus-related Cirrhosis: A Post Hoc Analysis Based on Two Randomized Controlled Trials
Yanan Guo, Li Du, Qing Xie, Chuan Liu, Lianjun Xing, Wei Jiang, Bitao Chen, Ying Zhu, Xiaorong Chen, Jing Wang, Xiaolong Qi, Jing Lv, Chenghai Liu
Published online September 21, 2026
Journal of Translational Gastroenterology.
doi:10.14218/JTG.2026.00019
Abstract
Fuzheng Huayu, a patent herbal product, has shown promise in liver fibrosis and cirrhosis. The effect of Fuzheng Huayu on portal hypertension due to cirrhosis and the consequent
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Fuzheng Huayu, a patent herbal product, has shown promise in liver fibrosis and cirrhosis. The effect of Fuzheng Huayu on portal hypertension due to cirrhosis and the consequent complications needs further investigation. In this study, we aimed to evaluate the association of adjunctive Fuzheng Huayu plus entecavir with liver-related events and variceal regression in patients with compensated HBV-related cirrhosis.
A post hoc analysis was conducted using data from two randomized controlled trials implemented at eight clinical centers in China (ClinicalTrials.gov numbers: NCT02945982; NCT02945956). Patients with compensated hepatitis B virus-related cirrhosis were enrolled from October 2017 to March 2021. The primary endpoint was a composite of liver events and the individual components, including variceal bleeding, ascites, overt hepatic encephalopathy, and hepatocellular carcinoma.
A total of 218 participants (Fuzheng Huayu group: 110 and control group: 108; mean age, 51.5 years; 66.5% male; median observational follow-up time, 23.1 months) were included in the primary analysis. The occurrence of total liver events was less frequent in the Fuzheng Huayu group than in the control group (hazard ratio = 0.408 [0.187–0.892], P = 0.020). Among the individual components of liver events, the incidence of ascites was significantly lower in the Fuzheng Huayu group than in the control group (1.8% vs. 9.3%, P = 0.016). In addition, the rate of variceal regression was significantly higher in the Fuzheng Huayu group (27.3% vs. 10.2%, P < 0.001). Finally, there were no significant differences in the occurrence of adverse events between the two groups.
In this post hoc analysis of two randomized controlled trials, adjunctive Fuzheng Huayu plus entecavir was associated with fewer liver-related events, particularly ascites, and a higher rate of variceal regression than entecavir alone in patients with compensated hepatitis B virus-related cirrhosis. These findings warrant confirmation in adequately powered prospective studies.
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Original Article
Open Access
Integrated Single-cell and Bulk Transcriptome Analysis Characterizes a Candidate Ccl4/Lgals3/Egr1 Expression Pattern Associated with Immunometabolic Dysregulation in Traumatic Brain Injury
Tao Yang, Yongxiang Yang, Jingmin Cheng, Kexia Fan, Yuan Ma, Dongbo Zou, Sixun Yu
Published online September 18, 2026
Neurosurgical Subspecialties.
doi:10.14218/NSSS.2026.00014
Abstract
Traumatic brain injury (TBI) induces neuroimmune activation and metabolic reprogramming in microglia, but the transcriptional regulators underlying these responses remain unclear.
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Traumatic brain injury (TBI) induces neuroimmune activation and metabolic reprogramming in microglia, but the transcriptional regulators underlying these responses remain unclear. This study aimed to integrate single-cell and bulk transcriptomic datasets to identify microglia-associated regulatory genes and characterize their potential roles in post-TBI neuroinflammatory and immunometabolic dysregulation.
We integrated single-cell RNA sequencing data (GSE101901) with a bulk training dataset (GSE58485) and an independent bulk validation dataset (GSE242025) from murine TBI models. hdWGCNA, differential expression, pseudotime, CIBERSORT, and in silico transcription factor binding-site analyses were performed to identify and characterize candidate genes. Key-gene expression was additionally validated by RT-qPCR in male C57BL/6 mice assigned to Sham and TBI groups (n = 5 per group). The Drug Gene Interaction Database was used for exploratory drug-gene prediction.
Single-cell profiling suggested descriptive shifts in the proportions of microglia, astrocytes, and neurons after TBI. hdWGCNA identified 90 microglia-associated genes, 43 of which overlapped with nominally differentially expressed genes; 89 genes met the Benjamini–Hochberg-adjusted P < 0.05 threshold in the bulk analysis. Cross-dataset validation identified increased Ccl4 and Lgals3 expression and decreased Egr1 expression. Motif scanning identified four predicted EGR1 motif occurrences in the Ccl4 promoter and six occurrences at three unique locations in the Lgals3 promoter. RT-qPCR in TBI and Sham mice (n = 5 per group) supported the same directional expression changes in Ccl4, Lgals3, and Egr1.
A candidate Ccl4/Lgals3/Egr1 expression pattern characterized by Ccl4 and Lgals3 upregulation and Egr1 downregulation was associated with post-TBI neuroinflammatory and immunometabolic changes. Further mechanistic validation is required.
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Original Article
Open Access
National Epidemiological Trends in Hepatitis A–E Serologic and Virologic Markers in the United States, 2011–2023: A Population-Based Study
Zhao Li, Yuhua Chen, Yulan Zhu, Zhiwei Chen, Peng Hu
Published online September 29, 2026
Journal of Clinical and Translational Hepatology.
doi:10.14218/JCTH.2026.00708
Abstract
Viral hepatitis caused by A to E imposes a substantial global burden of liver disease. Despite US control strategies, long-term national data covering serologic markers of all five
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Viral hepatitis caused by A to E imposes a substantial global burden of liver disease. Despite US control strategies, long-term national data covering serologic markers of all five hepatitis viruses remain limited. In this study, we analyzed epidemiologic trends from 2011 to 2023 and aimed to identify prevention gaps.
We analyzed National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2023 using weighted logistic regression, with stratification by age, sex, and race/ethnicity.
Current hepatitis B virus (HBV) infection remained stable at 0.3%, while HBV susceptibility was 71.3%. Among individuals born in 1991 or later, HBV vaccination coverage declined from 90.0% to 83.6% during 2011–2020 (P for trend = 0.012); 57.0% of participants reporting vaccination were serologically susceptible. Anti-HDV positivity among participants with current HBV infection was 1.3%. Anti-hepatitis C virus (HCV) seroprevalence remained 1.6%, while active HCV viremia decreased from 0.8% to 0.4%, and viremia among anti-HCV-positive participants fell from 65.5% to 31.3% (P = 0.004). Hepatitis A virus antibody seroprevalence increased from 41.6% to 48.0% (P < 0.001) with stable vaccination coverage. Anti-HEV IgM positivity increased from 1.6% to 1.7% (P = 0.004).
US viral hepatitis trends diverged from 2011 to 2023. The decrease in detectable HCV RNA was consistent with progress in HCV control, whereas persistent HBV susceptibility, declining vaccination coverage in younger birth cohorts, and increasing hepatitis A virus seroprevalence and hepatitis E virus IgM positivity indicate ongoing prevention and surveillance needs.
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Guideline
Open Access
Evidence-based Guidelines for Standardized Pathologic Sampling and Diagnostic Reporting of Pancreatic Cancer in China
Hui Jiang, Yelin Yang, Yunshuo Zhang, Jianming Zheng
Published online September 28, 2026
Cancer Screening and Prevention.
doi:10.14218/CSP.2026.00001
Abstract
Standardized pathologic sampling and reporting are essential for pancreatic cancer staging, prognosis assessment, and comparable clinical data. This guideline aimed to develop evidence-based
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Standardized pathologic sampling and reporting are essential for pancreatic cancer staging, prognosis assessment, and comparable clinical data. This guideline aimed to develop evidence-based recommendations for standardized pathologic sampling and diagnostic reporting of pancreatic cancer in China. Literature searches were conducted in English and Chinese databases, guideline websites, Google, and reference lists for records published before December 31, 2023. Two investigators screened and extracted the evidence; methodological quality and certainty were assessed using AMSTAR/AGREE II and GRADE, respectively; and recommendations were formulated through two rounds of modified Delphi consultations, with an agreement threshold of ≥ 75% for consensus. The final guideline includes 11 recommendations, including six strong and five weak recommendations, addressing margin and surface assessment, sampling methods, histologic classification and grading, lymphovascular and perineural invasion, TNM staging, tumor regression grading after neoadjuvant therapy, background lesions, and structured reporting. These recommendations provide a standardized framework for pathologic assessment and reporting of pancreatic cancer resection specimens and may support more consistent prognostic evaluation and clinical decision-making.
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Original Article
Open Access
Biliary Duct Invasion in Colorectal Liver Metastases: Prevalence and Clinicopathologic Correlation in a Retrospective Cohort Study
Fatma Yildirim, Asuman Argon, Alper Uguz, Murat Sezak, Basak Doganavsargil, Murat Zeytunlu, Deniz Nart, Funda Yilmaz
Published online September 16, 2026
Journal of Clinical and Translational Pathology.
doi:10.14218/JCTP.2026.00027
Abstract
Biliary duct invasion (BDI) is an underrecognized growth pattern of colorectal cancer (CRC) liver metastases that can mimic intrahepatic cholangiocarcinoma or intraductal papillary
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Biliary duct invasion (BDI) is an underrecognized growth pattern of colorectal cancer (CRC) liver metastases that can mimic intrahepatic cholangiocarcinoma or intraductal papillary neoplasm of the bile duct. Its prevalence and clinicopathologic associations remain unclear. This study aimed to determine the prevalence of BDI and its clinicopathologic associations in surgically resected CRC liver metastases.
We retrospectively analyzed 133 consecutive patients who underwent hepatic resection for CRC liver metastases. Clinicopathologic variables, including age, sex, resection type, tumor differentiation, lymphovascular invasion (LVI), tumor budding, surgical margin status, and primary tumor characteristics, were compared between BDI-positive and BDI-negative cases. Categorical variables were analyzed using the chi-square, Fisher exact, or Fisher-Freeman-Halton exact test, as appropriate; continuous variables were analyzed using the Mann-Whitney U test.
BDI was identified in 19 of 133 cases (14.3%). Male sex showed the strongest numerical trend toward BDI (84.2% vs. 61.4%, P = 0.096), and LVI showed a nonsignificant numerical trend toward higher BDI rates (26.3% vs. 12.3%, P = 0.149). No clinicopathologic variable in the primary cohort analysis reached statistical significance after Bonferroni correction (α = 0.0050).
BDI occurs in approximately 14% of surgically resected CRC liver metastases in this cohort. Male sex and LVI show nonsignificant numerical trends toward higher BDI rates, but these findings should be interpreted cautiously given the limited sample size. Accurate histopathologic recognition of BDI and its distinction from intrahepatic cholangiocarcinoma remain important for correct pathologic diagnosis. Further prospective studies are warranted to clarify the clinicopathologic and prognostic significance of BDI.
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Review Article
Open Access
Transradial versus Transfemoral Access for Intracranial Aneurysm Embolization: A Narrative Review of Safety, Feasibility, and Current Evidence
Xiaofan Ye, Weihong Yang, Wilson Ho, Chaoyang Huang, Waisang Poon
Published online September 24, 2026
Neurosurgical Subspecialties.
doi:10.14218/NSSS.2026.00006
Abstract
Endovascular embolization is a cornerstone treatment for intracranial aneurysms, and transfemoral access (TFA) has traditionally been the default vascular route. Transradial access
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Endovascular embolization is a cornerstone treatment for intracranial aneurysms, and transfemoral access (TFA) has traditionally been the default vascular route. Transradial access (TRA) is increasingly used in neurointervention because it may reduce clinically important access-site complications, improve postprocedural comfort, and facilitate earlier ambulation. This narrative review aims to summarize direct and indirect evidence comparing TRA and TFA for intracranial aneurysm embolization, with attention to technical feasibility, access conversion, puncture-site complications, neurological events, radiation exposure, procedure duration, recovery, and cost considerations. Direct comparative evidence specific to aneurysm embolization remains limited and is mainly observational; some supporting data come from diagnostic cerebral angiography, mixed therapeutic neurointervention, and cardiovascular access literature. Available data suggest that TRA may be a safe and feasible option for selected patients when performed by experienced operators, particularly when radial anatomy is favorable and the intended device strategy is compatible with upper-extremity access. TFA remains essential for complex anatomy, large-bore device requirements, or insufficient TRA expertise. Access selection should therefore be individualized rather than based on a presumption of universal superiority. Well-designed multicenter studies are needed to define aneurysm-specific outcomes, long-term angiographic durability, patient-reported outcomes, and cost-effectiveness.
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Mini Review
Open Access
Colorectal Cancer Screening Pathways and Regional Prevention and Control in Primary Healthcare
Liwen Guan
Published online September 20, 2026
Cancer Screening and Prevention.
doi:10.14218/CSP.2026.00005
Abstract
Colorectal cancer is a major cause of cancer morbidity and mortality worldwide, including in China. Screening can facilitate earlier detection and reduce disease burden, while primary
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Colorectal cancer is a major cause of cancer morbidity and mortality worldwide, including in China. Screening can facilitate earlier detection and reduce disease burden, while primary healthcare institutions are central to population outreach, risk assessment, referral, and follow-up. However, resource constraints, limited public awareness, low screening adherence, and fragmented coordination continue to hinder implementation in community and rural settings. This mini review summarizes the epidemiological and health-economic rationale for colorectal cancer screening in primary healthcare and discusses organizational models, risk-stratified screening and referral, workforce training, quality control, data management, and information sharing. Available evidence supports coordinated pathways that link noninvasive initial screening to timely colonoscopy and follow-up, supported by clear governance, trained personnel, and traceable data systems. The ongoing Yazhou District program is included briefly as a descriptive example of how these components may be organized in practice. Future research should evaluate uptake, positivity, colonoscopy completion, lesion detection, adverse events, costs, and longer-term outcomes in diverse primary-care settings.
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