1.Advances in early diabetic neuroretinopathy
International Eye Science 2025;25(1):76-81
Diabetic retinopathy(DR)is a late-stage peripheral micro-neurovascular complication of chronic hyperglycemia, leading to blood-retinal barrier impairment and retinal dysfunction. Recent studies have found that diabetic neuroretinopathy(DN)may be one of the earliest events in diabetic retinal alterations. The main features include defective electroretinographic responses in newly diagnosed patients, early self-activation of microglia and Müller cells, reduced activity of neurotransmitters(e.g., DOPA/GABA), and early mitochondrial dysfunction, such as persistent Drp1-Fis1 fission and mtDNA methylation mismatches. Understanding the molecular basis of DN is essential for elucidating its pathogenesis and developing early treatments. This review summarizes pathological changes and mechanisms of retinal function, glial cells, neurotransmitters, mitochondria, and other factors in early diabetes mellitus, in order to provide a theoretical foundation for investigating early DN mechanisms and developing targeted therapies.
2.Mechanism of Xuefu Zhuyutang in Intervening in Ferroptosis in Rats with Coronary Heart Disease with Blood Stasis Syndrome Based on ACSL4 Signalling Pathway
Yi LIU ; Yang YANG ; Chang SU ; Peng TIAN ; Mingyun WANG ; Ruqian ZHONG ; Xuejiao XIE ; Qing YAN ; Qinghua PENG ; Qiuyan ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):27-38
ObjectiveTo investigate the mechanism of ferroptosis mediated by long-chain acyl-CoA synthetase 4 (ACSL4) signalling pathway in rats with coronary heart disease with blood stasis syndrome and the intervention effect of Xuefu Zhuyutang. MethodsSPF male SD rats were randomly divided into normal group, sham-operation group, model group, trimetazidine group (5.4 mg·kg-1), low-, medium-, and high-dose group (3.51, 7.02,14.04 g·kg-1) of Xuefu Zhuyutang. The coronary artery left anterior descending ligation method was used to prepare a model of coronary heart disease with blood stasis syndrome, and continuous treatment for 7 d was conducted, while the sham-operation group was only threaded and not ligated. The general macroscopic symptoms of the rats were observed, and indicators such as electrocardiogram, echocardiography, and blood rheology were detected. The pathological morphology of myocardial tissue was observed by hematoxylin-eosin (HE) staining, and the changes in mitochondria in myocardial tissue were observed by transmission electron microscopy. The level of iron deposition in myocardial tissue was observed by Prussian blue staining. The levels of 12-hydroxyeicosatetraenoic acid (12-HETE) and 15-HETE were detected in serum by enzyme-linked immunosorbent assay. A biochemical colourimetric assay was used to detect the levels of Fe2+, lipid peroxidation (LPO), glutathione (GSH), and T-GSH/glutathione disulfide (GSSG) in myocardial tissue. DCFH-DA fluorescence quantitative assay was employed to detect the levels of reactive oxygen species (ROS). Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was adopted to detect the protein and mRNA expressions of glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), ACSL4, and ly-sophosphatidylcholine acyltransferase3 (LPCAT3) in myocardial tissue. ResultsCompared with those in the normal group, the rats in the model group were poor in general macroscopic symptoms. The electrocardiogram showed widened QRS wave amplitude and increased voltage, bow-back elevation of the ST segments, elevated T waves, J-point elevation, and accelerated heart rate. Echocardiography showed a significant reduction in left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) (P<0.01). Blood rheology showed that the viscosity of the whole blood (low, medium, and high rate of shear) was significantly increased (P<0.01). HE staining showed an abnormal structure of myocardial tissue. There was a large area of myocardial necrosis and inflammatory cell infiltration and a large number of connective tissue between myocardial fibers. Transmission electron microscopy showed that the mitochondria were severely atrophy or swelling. The cristae were reduced or even broken, and the matrix was flocculent or even vacuolated. Prussian blue staining showed that there were a large number of iron-containing particles, and the iron deposition was obvious. The content of 12-HETE and 15-HETE in the serum was significantly increased (P<0.01). The content of Fe2+, LPO, and ROS in myocardial tissue was significantly increased (P<0.01). The content of GSH was significantly decreased (P<0.01), and T-GSH/GSSG was decreased (P<0.01). The protein and mRNA expressions of GPX4 and FTH1 in myocardial tissue were both significantly decreased (P<0.05, P<0.01), while those of ACSL4 and LPCAT3 increased significantly (P<0.01). Compared with the model group, the general macroscopic symptoms and electrocardiogram results of rats in low-, medium- and high-dose groups of Xuefu Zhuyutang were alleviated, and the differences in LVEF/LVFS ratios were all significantly increased (P<0.05, P<0.01). The differences in whole-blood viscosity (low, medium, and high rate of shear) were all significantly decreased (P<0.01). The results of HE staining and transmission electron microscopy showed that the morphology, structure, and mitochondria of cardiomyocytes were improved. The content of 12-HETE and 15-HETE in serum was reduced to different degrees in low-, medium-, and high-dose groups of Xuefu Zhuyutang (P<0.05, P<0.01). The content of Fe2+, LPO, and ROS was significantly reduced in the medium- and high-dose groups of Xuefu Zhuyutang (P<0.05, P<0.01), and the content of GSH and T-GSH/GSSG was significantly increased (P<0.05, P<0.01). The protein and mRNA expressions of GPX4 and FTH1 were significantly increased to varying degrees in the medium- and high-dose groups of Xuefu Zhuyutang (P<0.05, P<0.01), and ACSL4 and LPCAT3 were decreased to different degrees in the low-, medium-, and high-dose groups of Xuefu Zhuyutang (P<0.05, P<0.01). ConclusionXuefu Zhuyutang can regulate iron metabolism and anti-lipid oxidation reaction to mediate ferroptosis through the ACSL4 signalling pathway, thus exerting a protective effect on rats with coronary heart disease with blood stasis syndrome.
3.Effect Analysis of Different Interventions to Improve Neuroinflammation in The Treatment of Alzheimer’s Disease
Jiang-Hui SHAN ; Chao-Yang CHU ; Shi-Yu CHEN ; Zhi-Cheng LIN ; Yu-Yu ZHOU ; Tian-Yuan FANG ; Chu-Xia ZHANG ; Biao XIAO ; Kai XIE ; Qing-Juan WANG ; Zhi-Tao LIU ; Li-Ping LI
Progress in Biochemistry and Biophysics 2025;52(2):310-333
Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.
4.Standardization of outpatient medical record in rehabilitation setting
Ye LIU ; Qing QIN ; Haiyan YE ; Yifan TIAN ; Yingxin ZHANG ; Yaru YANG ; Zhongyan WANG ; Meng ZHANG ; Xiaoxie LIU ; Yanyan YANG ; Bin ZENG ; Mouwang ZHOU ; Yuxiao XIE ; Guangxu XU ; Jiejiao ZHENG ; Mingsheng ZHANG ; Xiangming YE ; Fubiao HUANG ; Qiuchen HUANG ; Yiji WANG ; Di CHEN ; Zhuoying QIU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(1):45-54
ObjectiveTo analyze the data structure and standards of rehabilitation outpatient medical records, to provide data support for improving the quality of rehabilitation outpatient care and developing medical insurance payment policies. MethodsBased on the normative documents issued by the National Health Commission, Basic Standards for Medical Record Writing and Standards for Electronic Medical Record Sharing Documents, in accordance with the Quality Management Regulations for Outpatient (Emergency) Diagnosis and Treatment Information Pages (Trial), reference to the framework of the World Health Organization Family of International Classifications (WHO-FICs), the data framework and content of rehabilitation outpatient medical records were determined, and the data standards were discussed. ResultsThis study constructed a data framework for rehabilitation outpatient medical records, including four main components: patient basic information, visit process information, diagnosis and treatment information, and cost information. Three major reference classifications of WHO-FICs, International Classification of Diseases, International Classification of Functioning, Disability and Health, and International Classification of Health Interventions,were used to establish diagnostic standards and standardized terminology, as well as coding disease diagnosis, functional description, functional assessment, and rehabilitation interventions, to improve the quality of data reporting, and level of quality control in rehabilitation. ConclusionThe structuring and standardization of rehabilitation outpatient medical records are the foundation for sharing of rehabilitation data. The using of the three major classifications of WHO-FICs is valuable for the terminology and coding of disease diagnosis, functional description and assessment, and intervention in rehabilitation outpatient medical records, which is significant for sharing and interconnectivity of rehabilitation outpatient data, as well as for optimizing the quality and safety of rehabilitation medical services.
5.Structure, content and data standardization of inpatient rehabilitation medical record summary sheet
Haiyan YE ; Qing QIN ; Ye LIU ; Yifan TIAN ; Yingxin ZHANG ; Yaru YANG ; Zhongyan WANG ; Meng ZHANG ; Xiaoxie LIU ; Yanyan YANG ; Bin ZENG ; Mouwang ZHOU ; Yuxiao XIE ; Guangxu XU ; Jiejiao ZHENG ; Mingsheng ZHANG ; Xiangming YE ; Fubiao HUANG ; Qiuchen HUANG ; Yiji WANG ; Di CHEN ; Zhuoying QIU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(1):55-66
ObjectiveTo explore the standardization of inpatient rehabilitation medical record summary sheet, encompassing its structure, content and data standards, to enhance the standardization level of inpatient rehabilitation medical record summary sheet, improve data reporting quality, and provide accurate data support for medical insurance payment, hospital performance evaluation, and rehabilitation discipline evaluation. MethodsBased on the relevant specifications of the National Health Commission's Basic Norms for Medical Record Writing, Specifications for Sharing Documents of Electronic Medical Records, and Quality Management and Control Indicators for Inpatient Medical Record Summary Sheet (2016 Edition), this study analyzed the structure and content of the inpatient rehabilitation medical record summary sheet. The study systematically applied the three major reference classifications of the World Health Organization Family of International Classifications, International Classification of Diseases (ICD-10/ICD-11, ICD-9-CM-3), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Interventions (ICHI Beta-3), for disease diagnosis, functional description and assessment, and rehabilitation intervention, forming a standardized terminology system and coding methods. ResultsThe inpatient rehabilitation medical record summary sheet covered four major sections: inpatient information, hospitalization information, diagnosis and treatment information, and cost information. ICD-10/ICD-11 were the standards and coding tools for admission and discharge diagnoses in the inpatient rehabilitation medical record summary sheet. The three functional assessment tools recommended by ICD-11, the 36-item version of World Health Organization Disability Assessment Schedule 2.0, Brief Model Disability Survey and Generic Functioning domains, as well as ICF, were used for rehabilitation functioning assessment and the coding of outcomes. ICHI Beta-3 and ICD-9-CM-3 were used for coding surgical procedures and operations in the medical record summary sheet, and also for coding rehabilitation intervention items. ConclusionThe inpatient rehabilitation medical record summary sheet is a summary of the relevant content of the rehabilitation medical record and a tool for reporting inpatient rehabilitation data. It needs to be refined and optimized according to the characteristics of rehabilitation, with necessary data supplemented. The application of ICD-11/ICD-10, ICF and ICHI Beta-3/ICD-9-CM-3 classification standards would comprehensively promote the accuracy of inpatient diagnosis of diseases and functions. Based on ICD-11 and ICF, relevant functional assessment result data would be added, and ICHI Beta-3/ICD-9-CM-3 should be used to code rehabilitation interventions. Improving the quality of rehabilitation medical records and inpatient rehabilitation medical record summary sheet is an important part of rehabilitation quality control, and also lays an evidence-based data foundation for the analysis and application of inpatient rehabilitation medical record summary sheet.
6.Application of single-cell RNA sequencing technology in Parkinson's disease
Ziyu LIU ; Dandan GENG ; Runjiao ZHANG ; Qing LIU ; Yibo LI ; Hongfang WANG ; Wenmeng XIE ; Wenyu WANG ; Jiaxin HAO ; Lei WANG
Chinese Journal of Tissue Engineering Research 2025;29(1):193-201
BACKGROUND:Parkinson's disease has the main pathological changes in the midbrain,especially in the dense substantia nigra,leading to impaired motor and non-motor function in patients.At present,research is limited by cellular heterogeneity,and its pathogenesis still needs to be further elucidated.In recent years,single-cell RNA sequencing(scRNA-seq)has gradually been applied in neurodegenerative diseases,which is of great significance for understanding intercellular heterogeneity,disease development mechanisms,and treatment strategies. OBJECTIVE:To review the research progress of scRNA-seq technology applied to Parkinson's disease in recent years,providing a theoretical basis for the application of scRNA-seq in the treatment and diagnosis of Parkinson's disease. METHODS:The first author used a computer system to search for relevant literature in the CNKI,WanFang,PubMed,and Web of Science databases,with the Chinese search terms"single-cell RNA sequencing,Parkinson's disease,cell heterogeneity,cell subtypes,dopaminergic neurons,glial cells"and English search terms"single-cell RNA seq,Parkinson disease,heterogenicity,subtypes,dopaminergic neurons,glial cells."71 articles were ultimately included for review and analysis. RESULTS AND CONCLUSION:(1)scRNA-seq is a high-throughput experimental technique that utilizes RNA sequencing at the single-cell level to quantify gene expression profiles in specific cell populations,revealing cellular mysteries at the molecular level.Compared with traditional sequencing techniques,scRNA-seq technology is used to reveal the diversity of cell types and changes in specific gene expression in complex tissues under various physiological and pathological conditions through automatic clustering analysis of cell transcriptome.(2)By using scRNA-seq,the development process of dopaminergic neurons and the unique functional characteristics of various cell subtypes are elucidated,in order to better understand potential therapeutic molecular targets.(3)The use of scRNA-seq analysis has improved our understanding of the response of Parkinson's disease glial cells,enabling us to comprehensively map and characterize different cell type populations,identify specific glial cell subpopulations related to neurodegeneration,and draw valuable single cell maps as reference data for future research.(4)The application of scRNA-seq to detect embryonic mice and stem cells will help improve the in vitro differentiation protocol and quality control of cell therapy,as well as evaluate the overall cell quality and developmental stage of dopaminergic neurons derived from stem cells.
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.Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306)
Chuan LIU ; Hong YOU ; Qing-Lei ZENG ; Yu Jun WONG ; Bingqiong WANG ; Ivica GRGUREVIC ; Chenghai LIU ; Hyung Joon YIM ; Wei GOU ; Bingtian DONG ; Shenghong JU ; Yanan GUO ; Qian YU ; Masashi HIROOKA ; Hirayuki ENOMOTO ; Amr Shaaban HANAFY ; Zhujun CAO ; Xiemin DONG ; Jing LV ; Tae Hyung KIM ; Yohei KOIZUMI ; Yoichi HIASA ; Takashi NISHIMURA ; Hiroko IIJIMA ; Chuanjun XU ; Erhei DAI ; Xiaoling LAN ; Changxiang LAI ; Shirong LIU ; Fang WANG ; Ying GUO ; Jiaojian LV ; Liting ZHANG ; Yuqing WANG ; Qing XIE ; Chuxiao SHAO ; Zhensheng LIU ; Federico RAVAIOLI ; Antonio COLECCHIA ; Jie LI ; Gao-Jun TENG ; Xiaolong QI
Clinical and Molecular Hepatology 2025;31(1):105-118
Background:
s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model.
Methods:
Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort.
Results:
In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM).
Conclusions
Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.
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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