1.Mechanism of Sangpi Zhike Prescription in Treating Cough After Respiratory Syncytial Virus Infection Based on "Lung-intestine Co-treatment" Theory
Chuang SUO ; Xiaohong BAI ; Zhitong YU ; Xue GONG ; Chan XIU ; Qihui LYU ; Zhihui LIU ; Kelin LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):126-137
ObjectiveTo explore the mechanism of Sangpi Zhike prescription in treating cough after respiratory syncytial virus (RSV) infection through the "lung-intestine co-treatment" approach using network pharmacology and animal experimental validation. MethodsActive ingredients and targets of Sangpi Zhike prescription were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Disease targets were obtained from GeneCards and Online Mendelian Inheritance in Man(OMIM) databases. Protein-protein interaction (PPI) networks and drug-component-target networks were constructed using overlapping targets between drugs and diseases to identify core targets. Gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analyses were performed on the overlapping targets. Sixty mouse models were established: 10 as the normal group, and the remaining mice were infected with RSV via slow nasal drip of RSV suspension, with cough induced using capsaicin solution. After modeling, mice were divided into a model group, a Montelukast Sodium group (1 mg·kg-1·d-1), and low, medium, and high dose groups of Sangpi Zhike prescription (4.875,9.75,and 19.5 g·kg-1·d-1), with 10 mice per group. From day 14 after RSV infection, the normal and model groups received saline via gavage, while other groups received corresponding drug treatments once daily for 5 d. Hematoxylin-eosin(HE) staining was used to observe pathological changes in lung and intestinal tissue. The protein content of extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylated (p)-ERK1/2 in the lung and colon tissue of mice was detected by Western blot. Real-time polymerase chain reaction(Real-time PCR) detected ERK1/2 mRNA expression in lung and intestinal tissue. Immunohistochemistry assessed p-MEK1/2, p-ERK1/2, p-c-Fos protein levels, and inflammatory cytokines interleukin(IL)-4 and (TNF)-α in lung and colon tissue. ResultsNetwork pharmacology identified 184 active ingredients and 684 targets in Sangpi Zhike prescription, with 1 344 RSV-related disease targets and 209 overlapping targets. Core targets included TNF, Fos, and Jun. KEGG enrichment revealed 179 pathways, primarily mitogen-activated protein kinase(MAPK), cancer, TNF, and IL-17 signaling pathways. Animal experiments showed that, compared to those of the normal group, the lung tissue sections of the model group showed typical inflammatory damage, infiltration of inflammatory cells, rupture of alveolar septa, extensive alveolar fusion, and disruption of tight junctions between single-layer columnar epithelial cells in the intestinal tissue. The values of p-ERK1/2 and ERK1/2 in lung and intestinal tissue were significantly increased (P<0.01), and the expression level of ERK1/2 mRNA was significantly elevated (P<0.01). The levels of ERK1/2, p-MEK1/2, p-ERK1/2, p-c-Fos, IL-4, and TNF-α along the ERK pathway were significantly increased (P<0.05, P<0.01). Compared to the model group, Sangpi Zhike prescription groups showed reduced lung and intestinal inflammation, decreased p-ERK1/2/ERK1/2 ratios (P<0.05,P<0.01), lower ERK1/2 mRNA levels, and downregulated ERK pathway proteins (P<0.05,P<0.01). ConclusionSangpi Zhike prescription alleviates cough and intestinal symptoms after RSV infection via the "lung-intestine co-treatment" mechanism by suppressing expression levels of ERK1/2, p-MEK1/2, p-ERK1/2, p-c-Fos, IL-4, and TNF-α on ERK pathway components, thereby mitigating lung and intestinal pathological damage.
2.Value of immunoglobulin G/immunoglobulin M ratio in predicting the prognosis of patients with initially unresectable hepatocellular carcinoma treated by transcatheter arterial chemoembolization combined with tyrosine kinase inhibitor and programmed cell death protein-1 inhibitor
Xingzhi LI ; Wei LUO ; Yuan FENG ; Yu CAI ; Xiaohong LIU ; Feixiang WU ; Yong PENG
Journal of Clinical Hepatology 2026;42(1):117-124
ObjectiveTo investigate the association between immunoglobulin G (IgG)/immunoglobulin M (IgM) ratio and prognosis in patients with initially unresectable hepatocellular carcinoma (iuHCC) receiving TTP triple therapy with transcatheter arterial chemoembolization (TACE), tyrosine kinase inhibitor (TKI), and programmed cell death protein-1 (PD-1) inhibitors. MethodsA retrospective analysis was performed for the clinical data of 151 iuHCC patients who received TTP triple therapy in Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, from November 2019 to December 2022, and according to IgG/IgM ratio, they were divided into high IgG/IgM group (IgG/IgM ratio >13.23) and low IgG/IgM group (IgG/IgM ratio ≤13.23). The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method and the log-rank test were used for survival analysis, and the Cox proportional hazards model was used to investigate the potential influencing factors for overall survival (OS). ResultsThe 151 patients had a median OS of 26.7 months (95% confidence interval [CI]: 19.8-not reached) and a median progression-free survival of 12.5 months (95%CI: 10.4 — 15.8). The objective response rate was 83.4% and the disease control rate was 94.0%. There were no significant differences in baseline data between the high IgG/IgM group and the low IgG/IgM group (all P>0.05). There was a significant difference in median OS between the high IgG/IgM group and the low IgG/IgM group (20.6 months vs not reached, P=0.016). In both the high IgG/IgM group and the low IgG/IgM group, salvage hepatectomy was significantly associated with the improvement in OS (χ2=8.297 and 10.307, both P<0.05). The multivariate analysis showed that high IgG/IgM ratio (hazard ratio [HR]=1.799, 95%CI: 1.077 — 3.006, P=0.025), baseline alpha-fetoprotein >400 ng/mL (HR=1.762, 95%CI: 1.017 — 3.050, P=0.043), and BCLC stage (HR=2.265, 95%CI: 1.212 — 4.232, P=0.010) were independent influencing factors for OS. ConclusionHigh IgG/IgM ratio is associated with a poorer prognosis in iuHCC patients receiving TTP triple therapy, and salvage hepatectomy has a potential value in improving the prognosis of patients with a high IgG/IGM ratio.
3.Curzerene Ameliorates Depression-Like Behaviors and Cognitive Impairment by Modulating the Gut Microbiota and HMGB1/RAGE/ TLR4 Pathway
Fengjing HUANG ; Xiaohong MA ; Xiao XU ; Jingwen ZHANG ; Chunlai WANG ; Ruoxi SONG ; Xiangxiang WANG ; Mingxing CHEN ; Yu QI
Biomolecules & Therapeutics 2026;34(1):174-188
Curzerene, a sesquiterpene compound isolated from Curcuma Radix, exhibits various therapeutic effects, such as anti-tumor and anti-hyperlipidemic properties. However, its neuroprotective effects have not yet been reported. This study focused on exploring the neuroprotective effect of curzerene and elucidating its potential mechanism by combining molecular biotechnology with multi-omics approaches. Curzerene was orally administered to LPS-induced depressive-like behaviors and cognitive impairment in mice for 14 days, and the related biochemical parameters were evaluated. The possible mechanisms were elucidated using qRT-PCR, Western Blot, immunofluorescence, untargeted metabolomics, GC-MS and 16S rDNA comprehensively. Curzerene ameliorated depression symptoms and cognitive impairment by increasing the preference for sucrose in SPT and the central area and total distance traveled in OFT, reducing the immobility time in TST and FST, as well as rising the spontaneous alternation ratio in Y maze. Multiple molecular biology techniques analyses indicated the ameliorative effect of curzerene via HMGB1/RAGE/ TLR4 pathway. Moreover, curzerene primarily regulates purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, pyrimidine metabolism, etc. Furthermore, intervention increased the relative abundance of Parabacteroides, Clostridia_UCG-014_unclassified, and Rhodospirillales_unclassified, and enhanced the production of SCFAs. This work demonstrated that curzerene effectively protects against LPS-induced neurological damage, potentially by inhibiting the HMGB1/ RAGE/TLR4 pathway through the restoration of gut microbiota homeostasis, modulation of metabolites, and enhancement of SCFAs. In conclusion, this study offers new perspectives on the therapeutic possibilities of curzerene in mitigating depressive-like behaviors and cognitive impairment.
4.Evaluation of CARIFS Score and Negative Antigen Conversion Rate of Qingxuan Daozhi Formula in Treatment of Influenza in Children (Heat Accumulation in Lung and Stomach Syndrome):A Multi-center Randomized Controlled Clinical Study
Jing WANG ; Liqun WU ; Tiegang LIU ; Yongning CAO ; Jing QIU ; Jing LI ; Huaqing TAN ; Ying ZHANG ; Xulei GOU ; Jia WANG ; Jing LI ; Haipeng CHEN ; Xueying QIN ; Yuanshuo TIAN ; Yang WANG ; Chen BAI ; Zhendong WANG ; Qianqian LI ; He YU ; Xueyan MA ; Fei DONG ; Lin JIANG ; Yingqi XU ; Jianping LIU ; Xiaohong GU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):188-196
ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children (heat accumulation in the lung and stomach syndrome). MethodsThrough a multi-center randomized controlled methodology design,confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals,such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days,and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale (CARIFS) and the incidence of complications,severe cases, and critical cases. Follow-up observation was conducted on the day of enrollment,48 hours after medication,72 hours after medication, and (6+1) d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group (90 cases) or the control group (90 cases). All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was (5.29±1.25) d,and that in the control group was (5.40±1.68) d,without a statistically significant difference. After five days of intervention,52 cases in the experimental group and 51 cases in the control group converted to negative,without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention,there were statistically significant differences between the experimental group and the control group in three dimensions, including headache,muscle soreness, and the need for extra care (P<0.05). On the (6+1) days after the intervention,the differences in both the experimental group and the control group were statistically significant in 10 dimensions, including sore throat,bad sleep,uncomfortable feeling,poor spirit and fatigue,crying more than usual,the need for extra care,symptom,function,influence on parents,and total score (P<0.05). The comparison results within the group in the dimensional scores of symptom, function, and influence on parents,as well as the CARIFS total score showed that with the delay of follow-up time,scores of both groups decreased significantly,with a statistically significant difference (P<0.01). Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention,the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up,the mean score of the experimental group was lower than that of the control group,with no statistically significant difference. In terms of the incidence of complications,severe cases, and critical cases, there were no complications,severe cases, and critical cases in the two groups,without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children (heat accumulation in the lung and stomach syndrome) are not inferior to Oseltamivir Phosphate granules, and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children (heat accumulation in the lung and stomach syndrome).
5.Qijia Rougan Decoction Ameliorates Liver Fibrosis Through miRNA-mRNA Network
Yumei WANG ; Peijie WU ; Shaoxiu JI ; Han YU ; Xiaohong ZUO ; Xiaofeng CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):84-90
ObjectiveTo explore the mechanism by which Qijia Rougan decoction ameliorates liver fibrosis through amino acid/fatty acid metabolic reprogramming and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway, based on the miRNA-mRNA regulatory network and the interaction between metabolism and signaling pathways. MethodsSprague-Dawley (SD) rats were randomized into four groups (n=8): control, model, and low-dose and high-dose (7.0, 28.0 g·kg-1·d-1, respectively) Qijia Rougan decoction. Liver fibrosis was induced by subcutaneous injection of carbon tetrachloride (CCl4). From week 9, drug intervention was implemented for 7 weeks. After the final administration, the pathological changes in the liver were evaluated through hematoxylin-eosin (HE) and picrosirius red (PSR) staining. An automated biochemical analyzer was used to measure the serum levels of biochemical indicators, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bile acid (TBA), albumin (ALB), and cholesterol (TC). High-throughput miRNA sequencing was performed to identify differentially expressed miRNAs (DemiRs) during liver fibrosis. A miRNA-mRNA interaction network was constructed to identify key targets, which were then subjected to GO and KEGG enrichment analyses. The expression levels of selected DemiRs were validated by Real-time PCR. ResultsCompared with the control group, the model group showed marked hepatic lobular necrosis, increased collagen deposition, significant fibrosis, elevated serum levels of ALT, AST, ALP, and TBA (P<0.01), and declined levels of ALB and TC (P<0.01). Compared with the model group, Qijia Rougan decoction treatment reduced hepatic necrosis, collagen accumulation, and fibrosis, lowered the serum levels of ALT, AST, ALP, and TBA (P<0.01), and raised the levels of ALB and TC (P<0.01). Integrated miRNA-seq and RNA-seq analysis identified 31 DemiRs (6 upregulated and 25 downregulated) and 498 targets. The expression trends of four selected DemiRs, including rno-miRNA-376b-3p, were consistent with sequencing results (R2=0.93). Functional annotation revealed that top 20 upregulated targets were enriched in amino acid and fatty acid metabolism, while top 20 downregulated targets were significantly associated with the PI3K/Akt signaling pathway and cancer progression. ConclusionQijia Rougan decoction alleviates liver fibrosis by reconstructing the miRNA-mRNA regulatory network, promoting metabolic reprogramming, and inhibiting the PI3K/Akt signaling pathway. These findings provide mechanism evidence supporting the multi-targeted antifibrotic effects of traditional Chinese medicine compound formulas.
6.Clinical Efficacy of Juanbitang Hot Compress Pack Combined with Intensive Rehabilitation Training in Ameliorating Hemiplegia After Stroke
Yuqin SHENG ; Yong YU ; Yan ZHANG ; Yuqing XIE ; Qing LIN ; Qian HU ; Longyu ZHANG ; Hongmei XU ; Xiaohong FAN ; Shouliang MA
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(17):210-218
ObjectiveTo explore the clinical efficacy of Juanbitang hot compress pack combined with intensive rehabilitation training in stroke patients with hemiplegia. MethodsA total of 80 stroke patients with hemiplegia were selected and assigned into a control group (40 cases) and an observation group (40 cases) according to the random number table method. The control group received conventional rehabilitation training and nursing intervention,while the observation group was additionally treated with Juanbitang hot compress pack. The two groups were compared in terms of the neurological function (national institute of health stroke scale score,NIHSS score),muscle strength,motor function (fugl-meyer assessment scale score,FMA score),daily living activity (modified barthel index,MBI),balance ability (berg balance scale score,BBS score),trunk control ability (Sheikh Trunk Control Test score,Sheikh TCT score),and homocysteine (Hcy) level before and after treatment. ResultsAfter treatment,the observation group had lower NIHSS score and Hcy level than the control group (P<0.05). The total response rate of the observation group (97.50%) was higher than that of the control group (77.50%). The scores of upper limb and lower limb FMA,MBI,BBS,and Sheikh TCT in the observation group were all higher than those in the control group (P<0.05). ConclusionThe application of Juanbitang hot compress pack combined with rehabilitation training can effectively improve the neurological function,muscle strength,motor function,daily living ability,balance ability,and trunk control ability and reduce the Hcy level in stroke patients with hemiplegia,demonstrating enhanced clinical efficacy.
7.Assessing type Ⅰ H.pylori for stratifying colorectal neoplasia risk in a gastroenterology clinic population
Ye YU ; Xia TIAN ; Meng LIU ; Xiaohong CHEN ; Meng WANG
Acta Universitatis Medicinalis Anhui 2026;61(7):1289-1295
ObjectiveTo investigate the relationship between TypeⅠHelicobacter pylori (H. pylori) infection and the risk of colorectal neoplasms (CRN) in patients attending gastroenterology clinics, and to evaluate its predictive value for CRN in this population. MethodsWe included 2 148 patients presenting to the Department of Gastroenterology, with 677 assigned to the CRN group and 1 471 to the non-CRN group.H.pylori antibody typing was performed using Western blot, with typeⅠdefined as positivity for CagA and/or VacA antibodies, and type II as positivity only for UreA/B antibodies. Statistical analyses included univariate screening, multivariate logistic regression, and receiver operating characteristic (ROC) curve evaluation. ResultsTypeⅠH.pylori seropositivity was significantly more prevalent in the CRN group than in the non-CRN group (54.51% vs 45.62%, Padjust<0.05). No significant differences were observed for type Ⅱ H.pylorior seronegative subjects. The CRN group had higher proportions of males, hypertension, diabetes, smoking, and alcohol use, as well as elevated body mass index, fasting plasma glucose, triglycerides, and uric acid, along with lower high-density lipoprotein levels (all P<0.05). Multivariate analysis confirmed typeⅠH.pylori (OR=1.303), alcohol consumption (OR=2.315), male (OR=1.592), and age (OR=1.048) as independent risk factors for CRN. Although type I H.pylori alone showed limited predictive value (AUC=0.544), a combined model incorporating alcohol use, age, and sex demonstrated significantly improved discriminative ability (AUC=0.681, sensitivity 59.1%, specificity 68.2%). ConclusionTypeⅠH. pylori infection predicts the risk of CRN in gastroenterology patients. Assessing it can help to optimize the identification of high-risk individuals and inform targeted screening strategies.
8.Effects of Shujin Jiannao Formula (舒筋健脑方) on Neural Repair and PI3K-Akt-mTOR Pathway of Brain Tissue in Cerebral Palsy Model Rats
Ruiqin YU ; Yanjun MO ; Houjun ZHANG ; Gang LIU ; Zhuoluo ZHOU ; Zechen RUAN ; Lin XU ; Xiaohong MU
Journal of Traditional Chinese Medicine 2025;66(10):1038-1045
ObjectiveTo explore the possible mechanisms of Shujin Jiannao Formula (舒筋健脑方) for cerebral palsy. MethodsThirty 7-day-old SD rats were randomly divided into normal group, model group, and Shujin Jiannao Formula group, with 10 rats in each group. The model group and Shujin Jiannao Formula group established a cerebral palsy model by the classic Rice-Vannucci method. After successful modeling, rats in Shujin Jiannao Formula group were given Shujin Jiannao Formula 16 g/(kg·d) by gavage, while the normal group and model group were given normal saline 10 ml/(kg·d) by gavage once a day. After one week of intervention, the rats' body weight was measured, and Zea-Longa scores, the righting reflex test, and the hindlimb suspension test were conducted for assessment; hematoxylin-eosin (HE) staining and Nissl staining were used to observe pathological changes in brain tissue, and the number of Nissl-positive neurons was counted; enzyme-linked immunosorbent assay (ELISA) was employed to measure levels of inflammatory cytokines in the brain tissue, specifically interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α); immunofluorescence was used to detect the expression levels of neurofilament protein 200 (NF200) and myelin basic protein (MBP) in brain tissue; Western Blot analysis was conducted to determine the protein levels of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt/PKB/Rac), and mammalian target of rapamycin (mTOR) in brain tissue. ResultsCompared with the normal group, rats in the model group showed significantly higher Zea-Longa scores and lower scores in the hindlimb suspension test (P<0.01); pathological findings revealed loose structure in the cerebral cortex, hippocampal atrophy, and neuronal damage in brain tissue. Levels of IL-1β and TNF-α elevated, and the number of Nissl-stained positive neurons in the cortex and hippocampal CA1 region reduced, and immunofluorescence intensity of NF200 and MBP, as well as protein expression levels of PI3K and mTOR, significantly decreased (P<0.05 or P<0.01). Compared with the model group, rats in Shujin Jiannao Formula group showed decreased Zea-Longa scores and increased hindlimb suspension test scores (P<0.05); pathological damage in brain tissue alleviated, levels of IL-1β and TNF-α reduced, the number of Nissl-stained positive neurons in the cortex and hippocampal CA1 region increased, and the immunofluorescence intensity of NF200 and MBP, as well as the protein levels of PI3K and mTOR, significantly elevated (P<0.05 or P<0.01). There were no statistically significant differences among the groups in body weight, body-turning time, or AKT protein levels in brain tissue (P>0.05). ConclusionShujin Jiannao Formula can improve the neurological function of rats with cerebral palsy, exert neurorestorative effects, and its mechanism of action may be related to the reduction of inflammatory response in brain tissue and the activation of the PI3K/AKT/mTOR signaling pathway.
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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