1.Editorial Explanation of Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-dampness Obstruction Syndrome and Dampness-heat Obstruction Syndrome
Na LIN ; Yanqiong ZHANG ; Changhong XIAO ; Shenghao TU ; Jianning SUN ; Shijun XU ; Xia MAO ; Representation Preparation GROUP
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):55-59
The Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-dampness Obstruction Syndrome and Dampness-heat Obstruction Syndrome (hereinafter referred to as the Guidelines) (No. T/CACM1567-2024) was published by Chinese Association of Chinese Medicine on January 11, 2024. To assist researchers and medical workers in understanding and applying the Guidelines more accurately, and also to provide reference and assistance for the establishment of guidelines on other types of diseases and syndromes combined with animal models, this paper made a declaration of the workflow, technological links, development references, promotion of its application and after-effect evaluation of the Guidelines that has been made according to the requirements of "Draft Group Standard of the Standardization Office of the Chinese Association of Traditional Chinese Medicine".
2.Combination of CT/MRI LI-RADS With Second-Line Contrast-Enhanced Ultrasound Using Sulfur Hexafluoride or Perfluorobutane for Diagnosing Hepatocellular Carcinoma in High-Risk Patients
Yu LI ; Sheng LI ; Qing LI ; Kai LI ; Jing HAN ; Siyue MAO ; Xiaohong XU ; Zhongzhen SU ; Yanling ZUO ; Shousong XIE ; Hong WEN ; Xuebin ZOU ; Jingxian SHEN ; Lingling LI ; Jianhua ZHOU
Korean Journal of Radiology 2025;26(4):346-359
Objective:
The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB).
Materials and Methods:
This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB.
Results:
In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%).
Conclusion
The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.
3.Effect of interleukin-8 regulation on monocyte chemotactic protein-1 secretion and expression through the NF-kappaB/p65 signaling pathway on the migration of residual epithelial cells in the lens capsule
Wei SI ; Su XU ; Yuhang ZHANG ; Yi MAO ; Keyu GUO ; Yanzhong HU ; Fengyan ZHANG
International Eye Science 2025;25(4):537-543
AIM: To investigate the effect of interleukin-8(IL-8)on the regulation of monocyte chemotactic protein-1(MCP-1)secreted by lens epithelial cells(LEC)during cell migration in the development of posterior capsule opacification(PCO).METHODS: A rat lens capsule model was established and cultured in medium supplemented with 10% fetal bovine serum. Upon migration of LEC to 30%-50% of the posterior capsule, serum was removed. The capsule was subsequently divided into two groups: a control group and an IL-8(15 ng/mL)treatment group. LEC migration was captured at multiple time points. The secretion and mRNA expression of MCP-1 were quantified using ELISA and RT-qPCR, respectively. Immunofluorescence was used to assess MCP-1 expression in the different experimental groups. SRA01/04 cells were divided into three groups: control, IL-8(15 ng/mL), and IL-8(15 ng/mL)+200 μmol/L Bindarit(BND)groups, with migration measured by the Transwell assay. Additionally, SRA01/04 cells were divided into negative control(NC), NC+15 ng/mL IL-8, and 15 ng/mL IL-8+p65 siRNA groups, and MCP-1 secretion and mRNA expression were further analyzed by ELISA and RT-qPCR.RESULTS:LEC migration in the rat lens capsule cultured in vitro showed that the cells migration of the 15 ng/mL IL-8 group significantly increased at 48, 72 and 96 h(all P<0.05). ELISA results revealed that MCP-1 levels in SRA01/04 cells from the 15 ng/mL IL-8-treated group were markedly higher than those in the control group at both 12 and 24 h(all P<0.05). RT-qPCR analysis also demonstrated a significant increase in MCP-1 mRNA expression in the 15 ng/mL IL-8 group at both time points(all P<0.05). Immunofluorescence staining indicated greater MCP-1 expression in capsular epithelial cells of the 15 ng/mL IL-8 group at 24 h(P=0.007). Transwell assays further confirmed increased cell migration in the 15 ng/mL IL-8 group compared to the control group(P=0.001), while the migration reduced in the 15 ng/mL IL-8+200 μmol/L BND group compared to the 15 ng/mL IL-8 group(P=0.003). Moreover, ELISA and RT-qPCR results demonstrated a significant increase in MCP-1 secretion and mRNA expression in the NC+15 ng/mL IL-8 group at both 12 and 24 h compared to the NC group(all P<0.01). In contrast, MCP-1 secretion and mRNA expression were reduced in the 15 ng/mL IL-8+p65 siRNA group compared to the NC+15 ng/mL IL-8 group at both time points(all P<0.01).CONCLUSION: IL-8 promotes the migration of residual epithelial cells and regulates the secretion and expression of MCP-1 in LEC. The mechanism underlying IL-8's effects appears to be mediated through the activation of the NF-κB/p65 signaling pathway.
4.Characteristics of T cells in the liver tissues of mice with nonalcoholic steatohepatitis
Ting MAO ; Mingyi XU ; Jiayi WANG
Journal of Clinical Hepatology 2025;41(3):461-468
ObjectiveTo investigate the heterogeneity and transcriptomic characteristics of T-cell subsets in the liver of mice with nonalcoholic steatohepatitis (NASH) at the single-cell level using single-cell RNA sequencing (scRNA-seq), and to provide a reference for studying the mechanism of action of T cells in NASH. MethodsSix male C57BL/6 mice were randomly divided into control group fed with regular diet and NASH group fed with methionine-choline-deficient (MCD) diet, with three mice in each group, and liver tissue was collected for scRNA-seq after 6 weeks of modeling. Specific differentially expressed genes were analyzed between T-cell subsets, and related analyses were performed, including dimension clustering, cell type annotation, t-distributed stochastic neighbor embedding (t-SNE), violin plot, gene ontology (GO) functional enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Immunofluorescent staining was used to observe the expression of the T cell marker Tcrα and the specific marker genes Tcf7 and Cxcr6 in the liver of mice in the two groups. The independent-samples t test was used for comparison of continuous data between two groups. ResultsTwo T cell subsets were identified in the liver of mice, and the percentage of cluster 6 decreased from 58.5% in the control group to 48.7% in the NASH group. The top four specific genes were Nsg2, Cd8b1, Cd8a, and Tcf7. Tcf7, a characteristic marker gene for cluster 6, was expressed in 65% of cells in cluster 6, and therefore, cluster 6 was defined as Tcf7+ T cells. The GO and KEGG enrichment analyses showed that the differentially expressed genes of cluster 6 were involved in T cell activation, leukocyte adhesion, binding ubiquitin-like protein ligase, and the signaling pathways for Th17, Th1, and Th2 cell differentiation. The percentage of cluster 7 increased from 41.5% in the control group to 51.3% in the NASH group. The top four specific genes of cluster 7 were Cd40lg, Tcrg-C1, Il2rα, and Cxcr6. Cxcr6 was expressed in 90% of cells in cluster 7, and therefore, cluster 7 was defined as Cxcr6+ T cells. The GO and KEGG enrichment analyses showed that cluster 7 was involved in T cell activation, cytokine production, the T cell receptor signaling pathway, and the Th17 cell differentiation and MAPK signaling pathway. Immunofluorescence assay showed that compared with the control group, the NASH group showed a significant reduction in the area with positive co-expression of Tcf7 protein and Tcrα protein (1.80%±0.67% vs 0.33%±0.13%, P<0.05) and a significant increase in the area with positive co-expression of Cxcr6 protein and Tcrα protein (0.50%±0.09% vs 2.66%± 0.33%, P<0.001). ConclusionThere is a reduction in the percentage of Tcf7+ T cells and an increase in the percentage of Cxcr6+ T cells in NASH mice, revealing the characteristics and differences of T cells in the liver of NASH mice.
5.Organizational Readiness for Change and Factors Influencing the Implementation of Shared Medical Appointment for Diabetes in Primary Healthcare Institutions
Wei YANG ; Yiyuan CAI ; Jiajia CHEN ; Run MAO ; Lang LINGHU ; Sensen LYU ; Dong XU
Medical Journal of Peking Union Medical College Hospital 2025;16(2):479-491
The success of implementation research is closely tied to the institution's pre-implementation readiness. This study aims to explore the organizational readiness for change (ORC) and its influencing factors on primary healthcare settings in the implementation of the "Shared Medical Appointment for Diabetes (SMART) in China: design of an optimization trial" and to enhance ORC and provide insights to support the effective implementation of the program. Qualitative interviews and quantitative surveys were conducted to evaluate the ORC level and its influencing factors in 12 institutions implementing the SMART program. The Scale for Assessing the Institution's Readiness to Implement Evidence-Based Practices was utilized to measure ORC levels. Qualitative interviews were conducted among change implementers to gather information regarding the status of influencing factors. Thematic analysis was applied to extract factors from the interview data, and an assessment questionnaire was developed to measure the perceived impact of these factors. A fuzzy-set qualitative comparative analysis (fsQCA) method was employed to identify the influencing factors of ORC and pathways leading to high-level ORC. Seventy implementers from 12 institutions, encompassing administrators, clinicians, and health managers, participated in the interviews and surveys. The median and interquartile of the ORC scores were 105.20 (101.23, 107.33). The fsQCA indicated that a clear understanding of specific tasks and responsibilities, the active engagement of key participants, sufficient preliminary preparation, and the use of audits and feedback mechanisms were critical pathways to a high-level ORC. Conversely, institutions lacking key participants, preliminary preparation, or marginal influence demonstrated a low-level ORC. Before implementing innovation, Coherence and Cognitive Participation were identified as critical factors in influencing ORC. Strong leadership from key participants played pivotal role in enhancing readiness for change and was essential for improving implementation fidelity and overall program success.
6.Mechanisms of Gut Microbiota Influencing Reproductive Function via The Gut-Gonadal Axis
Ya-Qi ZHAO ; Li-Li QI ; Jin-Bo WANG ; Xu-Qi HU ; Meng-Ting WANG ; Hai-Guang MAO ; Qiu-Zhen SUN
Progress in Biochemistry and Biophysics 2025;52(5):1152-1164
Reproductive system diseases are among the primary contributors to the decline in social fertility rates and the intensification of aging, posing significant threats to both physical and mental health, as well as quality of life. Recent research has revealed the substantial potential of the gut microbiota in improving reproductive system diseases. Under healthy conditions, the gut microbiota maintains a dynamic balance, whereas dysfunction can trigger immune-inflammatory responses, metabolic disorders, and other issues, subsequently leading to reproductive system diseases through the gut-gonadal axis. Reproductive diseases, in turn, can exacerbate gut microbiota imbalance. This article reviews the impact of the gut microbiota and its metabolites on both male and female reproductive systems, analyzing changes in typical gut microorganisms and their metabolites related to reproductive function. The composition, diversity, and metabolites of gut bacteria, such as Bacteroides, Prevotella, and Firmicutes, including short-chain fatty acids, 5-hydroxytryptamine, γ-aminobutyric acid, and bile acids, are closely linked to reproductive function. As reproductive diseases develop, intestinal immune function typically undergoes changes, and the expression levels of immune-related factors, such as Toll-like receptors and inflammatory cytokines (including IL-6, TNF-α, and TGF-β), also vary. The gut microbiota and its metabolites influence reproductive hormones such as estrogen, luteinizing hormone, and testosterone, thereby affecting folliculogenesis and spermatogenesis. Additionally, the metabolism and absorption of vitamins can also impact spermatogenesis through the gut-testis axis. As the relationship between the gut microbiota and reproductive diseases becomes clearer, targeted regulation of the gut microbiota can be employed to address reproductive system issues in both humans and animals. This article discusses the regulation of the gut microbiota and intestinal immune function through microecological preparations, fecal microbiota transplantation, and drug therapy to treat reproductive diseases. Microbial preparations and drug therapy can help maintain the intestinal barrier and reduce chronic inflammation. Fecal microbiota transplantation involves transferring feces from healthy individuals into the recipient’s intestine, enhancing mucosal integrity and increasing microbial diversity. This article also delves into the underlying mechanisms by which the gut microbiota influences reproductive capacity through the gut-gonadal axis and explores the latest research in diagnosing and treating reproductive diseases using gut microbiota. The goal is to restore reproductive capacity by targeting the regulation of the gut microbiota. While the gut microbiota holds promise as a therapeutic target for reproductive diseases, several challenges remain. First, research on the association between gut microbiota and reproductive diseases is insufficient to establish a clear causal relationship, which is essential for proposing effective therapeutic methods targeting the gut microbiota. Second, although gut microbiota metabolites can influence lipid, glucose, and hormone synthesis and metabolism via various signaling pathways—thereby indirectly affecting ovarian and testicular function—more in-depth research is required to understand the direct effects of these metabolites on germ cells or granulosa cells. Lastly, the specific efficacy of gut microbiota in treating reproductive diseases is influenced by multiple factors, necessitating further mechanistic research and clinical studies to validate and optimize treatment regimens.
7.Localization and Content Validation of the Organizational Readiness of Implementing Evidence-based Practices Scale
Jiajia CHEN ; Yiyuan CAI ; Wei YANG ; Run MAO ; Lang LINGHU ; Dong XU
Medical Journal of Peking Union Medical College Hospital 2025;16(3):765-776
This study aimed to localize the workplace readiness questionnaire (WRQ) and validate its applicability for assessing readiness for implementation of evidence-based practices (EBP) in primary care settings in China. The localization of the instrument will provide a practical instrument for assessing organizational readiness for change (ORC). The WRQ was translateed into Chinese version using the modified Brislin translation model, and its cross-cultural validity, content validity, and generalizability were evaluated by the Delphi method, and the expert feedback was evaluated using the item-level content validity index (I-CVI), scale-level content validity index (S-CVI), and corrected Kappa value. The index weights were evaluated by the analytic hierarchical process (AHP). The target users of the scale were invited to quantitatively evaluate its item importance score (IIS), and the surface validity was evaluated by combining the qualitative feedback from their cognitive interviews. To clarify the purpose of the scale, we revised its name to the Organizational Readiness of Implementing Evidence-Based Practices (ORIEBP) Scale. The ORIEBP scale contained five dimensions, which were Change Context, Change Valence, Information Evaluation, Change Commitment, Change Efficiency, and 32 items. After two rounds of the Delphi method to refine the construction of three dimensions and expressions of 11 items, the I-CVI were from 0.73 to 1.00, the Kappa value were from 0.70 to 1.00, and the S-CVI was over 0.92. All evaluation matrices of the hierarchical analysis method met the requirement of consistency ratio (CR < 0.1), and the weights of five dimensions were 0.2083, 0.2022, 0.1907, 0.2193, and 0.1795, in sequence. Nine out of eleven experts identified that items were applicable to other readiness assessment scenarios. The IIS scores for the five dimensions and 32 items were ranged from 2.93 to 3.54, and 2.71 to 3.42, presenting good face validity. The cognitive interview results showed that professional expressions were complex to understand. This study validated the ORIEBP scale and has good content validity and generalizability. The scale can be further improved by expanding its scope of use and validating its structure validity and reliability in different settings.
8.Combination of CT/MRI LI-RADS With Second-Line Contrast-Enhanced Ultrasound Using Sulfur Hexafluoride or Perfluorobutane for Diagnosing Hepatocellular Carcinoma in High-Risk Patients
Yu LI ; Sheng LI ; Qing LI ; Kai LI ; Jing HAN ; Siyue MAO ; Xiaohong XU ; Zhongzhen SU ; Yanling ZUO ; Shousong XIE ; Hong WEN ; Xuebin ZOU ; Jingxian SHEN ; Lingling LI ; Jianhua ZHOU
Korean Journal of Radiology 2025;26(4):346-359
Objective:
The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB).
Materials and Methods:
This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB.
Results:
In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%).
Conclusion
The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.
9.Combination of CT/MRI LI-RADS With Second-Line Contrast-Enhanced Ultrasound Using Sulfur Hexafluoride or Perfluorobutane for Diagnosing Hepatocellular Carcinoma in High-Risk Patients
Yu LI ; Sheng LI ; Qing LI ; Kai LI ; Jing HAN ; Siyue MAO ; Xiaohong XU ; Zhongzhen SU ; Yanling ZUO ; Shousong XIE ; Hong WEN ; Xuebin ZOU ; Jingxian SHEN ; Lingling LI ; Jianhua ZHOU
Korean Journal of Radiology 2025;26(4):346-359
Objective:
The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB).
Materials and Methods:
This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB.
Results:
In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%).
Conclusion
The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.
10.Combination of CT/MRI LI-RADS With Second-Line Contrast-Enhanced Ultrasound Using Sulfur Hexafluoride or Perfluorobutane for Diagnosing Hepatocellular Carcinoma in High-Risk Patients
Yu LI ; Sheng LI ; Qing LI ; Kai LI ; Jing HAN ; Siyue MAO ; Xiaohong XU ; Zhongzhen SU ; Yanling ZUO ; Shousong XIE ; Hong WEN ; Xuebin ZOU ; Jingxian SHEN ; Lingling LI ; Jianhua ZHOU
Korean Journal of Radiology 2025;26(4):346-359
Objective:
The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB).
Materials and Methods:
This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB.
Results:
In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%).
Conclusion
The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

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