1.Effect and Mechanism of Angelicae Sinensis Radix-Polygonati Rhizoma Herb Pair in Treatment of Simple Obesity
Wenjing LI ; Zhongyu WANG ; Yongxin HUANG ; Jingjing XU ; Ying DING ; You WU ; Zhiwei QI ; Ruifeng YANG ; Xiaotong YANG ; Lili WU ; Lingling QIN ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):70-79
ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma (ASR-PR) herb pair in the treatment of simple obesity through network pharmacology and molecular docking, and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Targets related to simple obesity were identified by retrieving the GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledgebase (PharmGKB), and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction (PPI) network, and topological analysis was conducted to identify core genes. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR (2.06 g·kg-1), PR (2.06 g·kg-1), or ASR-PR (4.11 g·kg-1) for 10 weeks, while the model group received an equal volume of purified water by gavage. After the administration period, the mice were sacrificed to measure body fat weight and serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Hematoxylin-eosin (HE) staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA), and the mRNA expression levels of epidermal growth factor receptor (EGFR) and signal transducer and activator of transcription 3 (STAT3) in liver tissue were detected by real-time quantitative polymerase chain reaction (Real-time PCR). ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 (Siberian glycoside A_qt), MOL003889 (methyl protodioscin_qt), MOL009766 (resveratrol), MOL006331 (4′,5-dihydroxyflavone), and MOL004941 (baicalin), thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group, the model group had significantly increased body weight, body fat weight, and serum levels of TG, TC, TNF-α, IL-6, and leptin (P<0.01). EGFR mRNA expression was significantly elevated (P<0.05), while STAT3 mRNA expression was significantly decreased (P<0.01). Histological analysis revealed disordered hepatic architecture in the model group, with pronounced lipid vacuoles, cytoplasmic loosening, lipid accumulation, and steatosis. Adipocytes in white adipose tissue (WAT) and brown adipose tissue (BAT) of the model group exhibited markedly increased diameters, reduced cell counts per unit area, and irregular morphology. Compared with the model group, the ASR-PR group significantly reduced body weight, body fat weight, serum TC, IL-6, TNF-α, leptin levels, and EGFR mRNA expression (P<0.01). TG levels were also significantly decreased (P<0.05), while STAT3 mRNA expression was significantly increased (P<0.01). Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased, and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components, modulate the PI3K/Akt and JAK/STAT signaling pathways, repair damaged liver and adipose tissues, and thereby alleviate the progression of obesity in mice.
2.Traditional Chinese Medicine Intervention in Diabetic Nephropathy Based on PI3K/Akt Signaling Pathway: A Review
Miao XU ; Xiaolei JIA ; Lingling QIN ; Haiyan WANG ; You WANG ; Yuzhuo CHANG ; Cuiyan LYU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):90-97
Diabetic nephropathy (DN) is a renal disorder induced by prolonged hyperglycemia, with major pathological features including persistent albuminuria, progressive decline in glomerular filtration rate, and elevated arterial blood pressure. As one of the most common and severe microvascular complications of diabetes, the pathogenesis of DN is complex and multifactorial. Without timely and effective treatment, DN may eventually progress to end-stage renal disease (ESRD). Currently available therapeutic options are often associated with significant adverse effects and high costs, and a large number of patients still progress to ESRD due to delayed treatment. Therefore, there is an urgent need for safer and more effective treatment strategies to improve the living standards and enhance the survival and quality of life of patients with DN. Modern studies have demonstrated that the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway plays a critical role in oxidative stress, inflammatory responses, autophagy, and glycolysis, and is closely associated with the pathophysiological progression of DN. In recent years, traditional Chinese medicine (TCM) has achieved remarkable progress in the prevention and treatment of DN, supported by rich clinical experience and confirmed therapeutic efficacy. With its characteristics of multi-target, multi-component, and multi-pathway actions, along with minimal side effects, TCM can delay the progression of DN and alleviate patient symptoms. Among these mechanisms, the regulation of the PI3K/Akt signaling pathway has gradually become a research hotspot. This paper systematically reviews the role and mechanisms of the PI3K/Akt signaling pathway in the onset and progression of DN based on extensive literature research, summarizes the latest research advances on the precise modulation of the PI3K/Akt pathway by Chinese medicine monomers, active constituents, Chinese patent medicines, and herbal compound formulas in the treatment of DN, aiming to provide a strong theoretical reference for the development of clinically effective agents for DN prevention and treatment.
3.Effect and Mechanism of Angelicae Sinensis Radix-Polygonati Rhizoma Herb Pair in Treatment of Simple Obesity
Wenjing LI ; Zhongyu WANG ; Yongxin HUANG ; Jingjing XU ; Ying DING ; You WU ; Zhiwei QI ; Ruifeng YANG ; Xiaotong YANG ; Lili WU ; Lingling QIN ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):70-79
ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma (ASR-PR) herb pair in the treatment of simple obesity through network pharmacology and molecular docking, and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Targets related to simple obesity were identified by retrieving the GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledgebase (PharmGKB), and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction (PPI) network, and topological analysis was conducted to identify core genes. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR (2.06 g·kg-1), PR (2.06 g·kg-1), or ASR-PR (4.11 g·kg-1) for 10 weeks, while the model group received an equal volume of purified water by gavage. After the administration period, the mice were sacrificed to measure body fat weight and serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Hematoxylin-eosin (HE) staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA), and the mRNA expression levels of epidermal growth factor receptor (EGFR) and signal transducer and activator of transcription 3 (STAT3) in liver tissue were detected by real-time quantitative polymerase chain reaction (Real-time PCR). ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 (Siberian glycoside A_qt), MOL003889 (methyl protodioscin_qt), MOL009766 (resveratrol), MOL006331 (4′,5-dihydroxyflavone), and MOL004941 (baicalin), thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group, the model group had significantly increased body weight, body fat weight, and serum levels of TG, TC, TNF-α, IL-6, and leptin (P<0.01). EGFR mRNA expression was significantly elevated (P<0.05), while STAT3 mRNA expression was significantly decreased (P<0.01). Histological analysis revealed disordered hepatic architecture in the model group, with pronounced lipid vacuoles, cytoplasmic loosening, lipid accumulation, and steatosis. Adipocytes in white adipose tissue (WAT) and brown adipose tissue (BAT) of the model group exhibited markedly increased diameters, reduced cell counts per unit area, and irregular morphology. Compared with the model group, the ASR-PR group significantly reduced body weight, body fat weight, serum TC, IL-6, TNF-α, leptin levels, and EGFR mRNA expression (P<0.01). TG levels were also significantly decreased (P<0.05), while STAT3 mRNA expression was significantly increased (P<0.01). Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased, and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components, modulate the PI3K/Akt and JAK/STAT signaling pathways, repair damaged liver and adipose tissues, and thereby alleviate the progression of obesity in mice.
4.Traditional Chinese Medicine Intervention in Diabetic Nephropathy Based on PI3K/Akt Signaling Pathway: A Review
Miao XU ; Xiaolei JIA ; Lingling QIN ; Haiyan WANG ; You WANG ; Yuzhuo CHANG ; Cuiyan LYU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):90-97
Diabetic nephropathy (DN) is a renal disorder induced by prolonged hyperglycemia, with major pathological features including persistent albuminuria, progressive decline in glomerular filtration rate, and elevated arterial blood pressure. As one of the most common and severe microvascular complications of diabetes, the pathogenesis of DN is complex and multifactorial. Without timely and effective treatment, DN may eventually progress to end-stage renal disease (ESRD). Currently available therapeutic options are often associated with significant adverse effects and high costs, and a large number of patients still progress to ESRD due to delayed treatment. Therefore, there is an urgent need for safer and more effective treatment strategies to improve the living standards and enhance the survival and quality of life of patients with DN. Modern studies have demonstrated that the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway plays a critical role in oxidative stress, inflammatory responses, autophagy, and glycolysis, and is closely associated with the pathophysiological progression of DN. In recent years, traditional Chinese medicine (TCM) has achieved remarkable progress in the prevention and treatment of DN, supported by rich clinical experience and confirmed therapeutic efficacy. With its characteristics of multi-target, multi-component, and multi-pathway actions, along with minimal side effects, TCM can delay the progression of DN and alleviate patient symptoms. Among these mechanisms, the regulation of the PI3K/Akt signaling pathway has gradually become a research hotspot. This paper systematically reviews the role and mechanisms of the PI3K/Akt signaling pathway in the onset and progression of DN based on extensive literature research, summarizes the latest research advances on the precise modulation of the PI3K/Akt pathway by Chinese medicine monomers, active constituents, Chinese patent medicines, and herbal compound formulas in the treatment of DN, aiming to provide a strong theoretical reference for the development of clinically effective agents for DN prevention and treatment.
5.History, Experience, Opportunities, and Challenges in Esophageal Cancer Prevention and Treatment in Linxian, Henan Province, A High Incidence Area for Esophageal Cancer
Lidong WANG ; Xiaoqian ZHANG ; Xin SONG ; Xueke ZHAO ; Duo YOU ; Lingling LEI ; Ruihua XU ; Jin HUANG ; Wenli HAN ; Ran WANG ; Qide BAO ; Aifang JI ; Lei MA ; Shegan GAO
Cancer Research on Prevention and Treatment 2025;52(4):251-255
Linxian County in Henan Province, Northern China is known as the region with the highest incidence and mortality rate of esophageal cancer worldwide. Since 1959, the Henan medical team has conducted field work on esophageal cancer prevention and treatment in Linxian. Through three generations of effort exerted by oncologists over 65 years of research on esophageal cancer prevention and treatment in Linxian, the incidence rate of esophageal squamous cell carcinoma in this area has dropped by nearly 50%, and the 5-year survival rate has increased to 40%, reaching the international leading
6.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.
7.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.
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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