1.Progress of researches on mechanisms underlying immune escape of Plasmodium
Yuhuang WU ; Jing HE ; Xinghang CAO ; Juntong LI ; Shuchu SHEN ; Youqin DU ; Chao TAN
Chinese Journal of Schistosomiasis Control 2025;37(3):325-331
		                        		
		                        			
		                        			 Malaria, a parasitic disease caused by infection with the species of Plasmodium and transmitted by Anopheles mosquito bites, is one of the major public health challenges that seriously threaten human health. Malaria parasites present diverse immune escape strategies to escape from the recognition and clearance of the host immune system, which poses a great challenge to the malaria control programme. This review presents the advances in the mechanisms underlying the immune escape of Plasmodium, including antigenic variation, epigenetic regulation, antagonism against IgM antibody, activation of the cyclic guanosine monophosphate-adenosine monophosphate (GMP-AMP) synthase-stimulator of interferon genes (cGAS-STING) signaling, suppression of splenic immune functions, and molecular camouflage, so as to provide insights into development of malaria vaccines and antimalarial agents and formulation of the malaria control strategy. 
		                        		
		                        		
		                        		
		                        	
2.Effects of Xiaozhong Zhitong Mixture (消肿止痛合剂) on Angiogenesis and the Dll4/Notch1 Signaling Pathway in Wound Tissue of Diabetic Foot Ulcer Model Rats
Xiao HAN ; Tao LIU ; Yuan SONG ; Jie CHEN ; Jiaxuan SHEN ; Jing QIAO ; Hengjie WANG ; Lewen WU ; Yazhou ZHAO
Journal of Traditional Chinese Medicine 2025;66(16):1695-1703
		                        		
		                        			
		                        			ObjectiveTo investigate the potential machanism of Xiaozhong Zhitong Mixture (消肿止痛合剂, XZM) in the treatment of diabetes foot ulcer (DFU). MethodsFifty SD rats were randomly divided into blank group, model group, XZM group, inhibitor group, XZM plus inhibitor group (combination group), with 10 rats in each group. Except for the blank group, rats were fed with high-sugar, high-fat, high-cholesterol diet, intraperitoneally injected with streptozotocin, and subjected to skin defect to establish DFU model. After successful modeling, the XZM group and the combination group were given 1 ml/(100 g·d)of XZM by gavage, while the blank group, model group, and inhibitor group were all given an equal volume of 0.9% sodium chloride injection by gavage. Thirty minutes later, the inhibitor group and the combination group were intraperitoneally injected with 5 mg/(kg·d) of Notch1 inhibitor DAPT. All groups were treated once a day. After 14 days of administration, the skin tissue from the dorsal foot of the blank group rats and wound tissue from the other groups were collected. The pathological changes of granulation tissue in the wound were detected using hematoxylin eosin (HE) staining. The microvascular density (MVD) in wounds was detected through immunohistochemical staining. Real time fluorescence quantitative polymerase chain reaction (RT-PCR) and western blotting were used to detect the mRNA and protein levels of Notch1 homolog (Notch1), Delta-like ligand 4 (Dll4), Delta-like ligand 4 (VEGF), and angiopoietin 2 (Ang-2), respectively. ResultsHistological results showed that the epidermal structure in the dorsal foot skin tissue of the rats in the blank group was intact. In the wound tissue of the model group, the epidermis exhibited excessive keratinization, vacuolar cytoplasm, and a large number of inflammatory cells infiltrating the tissue, while in the XZM group, a large amount of scab formation was observed in the epidermis, with no significant inflammatory cell infiltration and a noticeable increase in fibroblasts. In the combination group and the inhibitor group, partial epidermal scab formation was observed in the wound tissue with a small amount of inflammatory cell infiltration. Compared to those in the blank group, the MVD in the wound tissue increased in the model group, as well as the mRNA expression and protein levels of Notch1 and Dll4, while VEGFA and Ang-2 mRNA expression and protein levels significantly decreased (P<0.05 or P<0.01). Compared to those in the model group, the MVD in the wound tissue of all medication groups significantly increased, and the mRNA and protein levels of Notch1 and Dll4 decreased, while VEGFA and Ang-2 mRNA expression and protein levels increased (P<0.05 or P<0.01). Compared to the XZM group, the inhibitor group and the combination group showed decreased MVD in wound tissue, increased Notch1 and Dll4 mRNA and protein levels, and decreased expression of VEGFA and Ang-2 mRNA and proteins (P<0.05 or P<0.01). ConclusionXZM can effectively promote wound healing in DFU rats, and its mechanism of action may be related to the inhibition of Dll4/Notch1 signaling pathway in the wound tissue, therey promoting angiogenesis. 
		                        		
		                        		
		                        		
		                        	
3.Effects of Zhimu (Anemarrhena asphodeloides)-Huangbai (Phellodendron amurense) Medicinal Pair on Femoral Microstructure and Osteogenic-Adipogenic Differentiation in Ovariectomized Osteoporosis Model Rats
Chuncai LI ; Mingxing YUAN ; Jiawei LI ; Jing DENG ; Chongyang SHEN ; Yuan LIU
Journal of Traditional Chinese Medicine 2025;66(16):1704-1710
		                        		
		                        			
		                        			ObjectiveTo investigate the potential mechanisms of Zhimu (Anemarrhena asphodeloides)-Huangbai (Phellodendron amurense) medicinal pair in alleviating postmenopausal osteoporosis (PMOP). MethodsSixty unpregnant female SD rats were randomly divided into five groups, blank group, model group, low-dose Zhimu-Huangbai group, high-dose Zhimu-Huangbai group, and estradiol group, with 12 rats in each group. Except for the blank group, all other groups had their ovaries removed to create PMOP rat models, while the blank group only had the fat tissue around the ovaries removed. One week after the ovarian removal, the low-dose and high-dose Zhimu-Huangbai groups received concentrated solution of Zhimu and Huangbai with 1.8, 7.2 g/(kg·d) via gavage, the estradiol group received estradiol solution 0.09 mg/(kg·d) via gavage, and the blank group and the model group received 10 ml/(kg·d) of normal saline via gavage, once daily for 12 weeks. Before sampling, the body mass of the rats was recorded, and uterine tissue was taken to calculate the uterine index. The levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum were detected by ELISA; micro CT was used to examine the parameters of femoral microstructure, including bone volume/tissue volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), bone mineral density (BMD), trabecular separation (Tb.Sp), and cortical bone area (Ct.Ar). HE staining was used to observe pathological changes in the femur; RT-qPCR was used to detect the mRNA expression of osteogenic-adipogenic differentiation-related factors in femoral tissue, including Runt-related transcription factor 2 (Runx2), bone morphogenetic protein 2 (BMP-2), peroxisome proliferator-activated receptor γ (PPARγ), chemerin and chemokine-like receptor 1 (CMKLR1). ResultsCompared with the blank group, the model group showed a significant increase in body mass, a significant decrease in the uterine index, BV/TV, Tb.N, Tb.Th and BMD, a significant increase in Tb.Sp, and serum IL-1β, IL-6, and TNF-α levels, a significant reduction of mRNA expression of Runx2 and BMP-2 in bone tissue, and a significant increased mRNA expression of PPARγ, chemerin, and CMKLR1 (P<0.01). HE staining revealed that the femoral tissue showed a reduction and sparsity of trabeculae, a significant enlargement of the medullary cavity, and a large number of fat cells. Compared to the model group, the low-dose, high-dose Zhimu-Huangbai groups, and estradiol group showed significant improvements in all the above-mentioned indicators (P<0.05 or P<0.01). HE staining revealed a significant increase in trabeculae, more organized arrangement, and a marked reduction in fat cells. Compared to low-dose Zhimu-Huangbai group, the high-dose Zhimu-Huangbai group exhibited a significant increase in the uterine index and BMD, and a significant reduction in body mass and PPARγ and Chemerin mRNA expression (P<0.05 or P<0.01). Compared to high-dose Zhimu-Huangbai group, the estradiol group showed a decrease in uterine index, BV/TV, Tb.N, Tb.Th, BMD, and BMP-2 mRNA expression, while the levels of IL-1β, TNF-α, and IL-6, as well as Tb.Sp and the mRNA expressions of PPARγ, chemerin, and CMKLR1 increased (P<0.05 or P<0.01). ConclusionThe Zhimu-Huangbai medicinal pair can alleviate PMOP bone loss, and its mechanism of action is related to reducing the levels of inflammatory factors, correcting the disorder of osteogenic-adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and promoting the differentiation of BMSCs into osteoblasts. 
		                        		
		                        		
		                        		
		                        	
4.Correlation between beverage dependence and sleep quality among college students
Chinese Journal of School Health 2025;46(8):1125-1129
		                        		
		                        			Objective:
		                        			To explore the relationship between beverage dependence and sleep quality among college students, providing empirical evidence for improving their sleep quality. 
		                        		
		                        			Methods:
		                        			From December 2024 to January 2025, a convenience sampling method was used to conduct a questionnaire survey among 3 974 college students from four universities in Anhui Province. The Beverage Addiction Scale for College Students (BASCS) was used to assess beverage dependence, and the Self rating Scale of Sleep(SRSS) was used to evaluate sleep quality. A multivariate Logistic regression model was employed to analyze the relationship between beverage dependence and sleep quality, and a restricted cubic spline model was used to examine the dose response relationship between the two. 
		                        		
		                        			Results:
		                        			The positive rate of beverage dependence symptoms among college students was 7.6%, with positive rates of 9.6%, 13.8%, and 7.4% for the withdrawal symptoms, health effects, and dependence symptoms dimensions, respectively. The detection rate of sleep disorders was 23.6%. Multivariate Logistic regression analysis showed that after adjusting for covariates such as grade, gender, and body mass index, compared with the no beverage dependence group, students with positive beverage dependence symptoms had a higher risk of sleep disorders( OR =3.71, 95% CI =2.87-4.80, P <0.01). The  OR (95% CI ) for sleep disorders among students with positive symptoms in the withdrawal symptoms, health effects, and dependence symptoms dimensions were 2.80(2.22-3.53), 2.38(1.95-2.91), and 2.45(1.89-3.18)(all  P <0.01). Further analysis using a restricted cubic spline model revealed that the overall beverage dependence score and its three dimensional scores were approximately linearly related to the risk of sleep disorders among college students (all nonlinear  P >0.05). 
		                        		
		                        			Conclusions
		                        			Beverage dependence is associated with sleep quality among college students. Schools should take multiple approaches, such as health education on beverage awareness, to improve students  sleep quality.
		                        		
		                        		
		                        		
		                        	
5.The diagnosis and testing of immune hemolytic anemia induced by ceftizoxime sodium drug-dependent antibodies
Jing WANG ; Yangyi XIE ; Sha JIN ; Wei SHEN ; Dong XIANG ; Zhongying WANG
Chinese Journal of Blood Transfusion 2025;38(9):1230-1235
		                        		
		                        			
		                        			Objective: To explore the laboratory testing methods and clinical management strategies for immune hemolytic anemia induced by Ceftizoxime sodium drug-dependent antibodies. Methods: Patient blood samples were subjected to blood typing, direct antiglobulin test, and unexpected antibody identification. Ceftizoxime sodium drug-dependent antibodies were detected using the immune complex method and drug-sensitized red cell method. The properties and titers of the drug antibodies were further assessed. Flow cytometry was used to assess the complement activation capacity of the drug antibodies in vitro. Results: Direct antiglobulin tests (IgG and C3d) were positive. Ceftizoxime sodium drug-dependent antibodies were identified using both the immune complex method and the sensitized red cell method, their titers significantly increased following the addition of the drug. Flow cytometry confirmed the complement activation capability of these antibodies and identified 30 minutes as the optimal time for activation in vitro. The patient's condition improved rapidly after drug withdrawal and supportive transfusion, resulting in a favorable outcome. Conclusion: Ceftizoxime sodium can cause drug-induced immune hemolytic anemia via complement activation mediated by drug-dependent antibodies. Serological testing is essential for diagnosing drug-induced hemolytic anemia. Clinicians should be vigilant for this adverse reaction. The offending drug must be promptly discontinued, and supportive care should be initiated upon the onset of symptoms.
		                        		
		                        		
		                        		
		                        	
6.Study on the mechanism of gossypol acetic acid in the treatment of uterine fibroids based on proteomics
Xin ZHANG ; Abulaiti GULISITAN ; Jing SHEN ; Pei ZHANG ; Zuwen MA ; Jun YAO
China Pharmacy 2025;36(3):318-323
		                        		
		                        			
		                        			OBJECTIVE To investigate the mechanism of gossypol acetic acid (GAA) in the treatment of uterine fibroids. METHODS Human leiomyoma cells SK-UT-1 were selected as objects to investigate the effects of different concentrations (5, 10, 20, 40, 80, 160 μmol/L) of GAA on the activities of cell proliferation. 4D-DIA proteomic detection and bioinformatics analysis were carried out to screen differential proteins. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis were performed. The expressions of top 3 proteins [N-myc downstream regulated gene 1 (NDRG1), epidermal growth factor receptor feedback inhibitor 1 (ERRFI1), CXC chemokine ligand 3 (CXCL3)] with differential fold changes in SK-UT-1 cells were determined. RESULTS 10-160 μmol/L GAA could significantly reduce the survival rate of SK- UT-1 cells (P<0.05). Proteomics results showed that a total of 921 differentially expressed proteins were obtained, including 254 up-regulated proteins and 667 down-regulated proteins. The differentially expressed proteins were mainly distributed in mitochondria, nucleus, extracellular matrix, etc. Bioinformatics results showed that differentially expressed proteins were mainly involved in signaling pathways such as PI3K/AKT (phosphoinositide 3-kinase/protein kinase B), MAPK (mitogen-activated protein kinase), TNF (tumor necrosis factor), etc., which mainly involved cell apoptosis, aging, and movement. GAA significantly decreased protein expressions of NDRG1 and CXCL3 (P<0.05), but increased protein expression of ERRFI1 (P<0.05). CONCLUSIONS The improvement effect of GAA on uterine fibroids may involve signaling pathways such as PI3K/AKT, MAPK, TNF, etc. It can improve the occurrence and development of uterine fibroids by downregulating the expressions of NDRG1 and CXCL3 proteins, upregulating the expression of ERRFI1 protein, and affecting the proliferation and apoptosis of uterine fibroid cells.
		                        		
		                        		
		                        		
		                        	
7.Mortality and life loss due to coronary heart disease and stroke in Wujiang District of Suzhou in 2011 - 2022
Siyi GUN ; Rongyan ZHANG ; Jianxin SHEN ; Mei YANG ; Xiaochu PENG ; Jing TANG ; Mengxiang CHEN
Journal of Public Health and Preventive Medicine 2025;36(2):100-104
		                        		
		                        			
		                        			Objective  To understand the mortality and potential life loss due to coronary heart disease (CHD) and stroke in Wujiang District, Suzhou from 2011 to 2022, and to provide strategies and basis for the prevention and treatment of CHD and stroke.  Methods  We collected the data of death cases due to CHD and stroke from the death monitoring system in Suzhou from 2011 to 2022. The mortality of CHD and stroke, potential years of life lost (potential years of life lost , PYLL), average years of life lost (average years of life lost , AYLL) and potential years of life lost rate (potential years of life lost rate , PYLLR) were calculated to analyze the development trend of death and disease burden of CHD and stroke.  Results  From 2011 to 2022, the crude mortality of CHD was 31.91/10 million, and that of stroke was 118.93/10 million. CHD and stroke mortality rates both showed an upward trend(P<0.05, a statistically significant trend). From 2011 to 2022, the mortality rate of CHD and stroke in Wujiang District increased rapidly with the increase of age. From 2011 to 2022, the disease burden caused by CHD totaled 11005 person-years, with PYLLR of 1.26% and AYLL of 12.34 years per person. The PYLL caused by stroke was 13 587.5 people-years, the PYLLR was 1.55%, and the AYLL was 8.93 years per person. PYLL, PYLLR and AYLL all decreased in women(P<0.05), with no significant change in men(P>0.05).  Conclusion   From 2011 to 2022, the mortality rate of CHD and stroke in Wujiang District appeared a tendency towards a rise, effective intervention and prevention measures should be taken among elderly and male residents.
		                        		
		                        		
		                        		
		                        	
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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