1.Application of Medicinal and Edible Materials in Proactive Health and Technological Responses to Population Aging: A Review
Cuiying QIN ; Zuchang GUO ; Jie ZHANG ; Haiyan LI ; Jiayi WANG ; Qiuyan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):258-267
In the strategic context of "healthy China", the concept of "medicine and food homology", rooted in the culture of traditional Chinese medicine (TCM), has received unprecedented attention. In response to population aging in China, the health of the elderly has become the focus of public health attention, and proactive health is the key to healthy aging. From the perspective of the application of medicinal and edible materials in proactive health and technological responses to population aging for the first time, this paper firstly provided a systematic overview of medicinal and edible materials and the policies related to proactive health. Second, it summarized the situation of modern technology that accelerates the research and development of medicinal and edible products, as well as the current situation of various modern biotechnologies that reveal the mechanism of action of medicinal and edible materials. Third, it discussed the application scenarios of medicinal and edible materials in proactive health and technological responses to population aging, as well as the future research and development of medicinal and edible materials. By exploring in depth the unique value and importance of medicinal and edible materials, the paper lays a theoretical foundation for improving the health care capabilities of TCM and contributes new strategies derived from TCM to healthy aging.
2.Establishment and Evaluation of Animal Model of Acute Myocardial Infarction with Syndrome of Qi and Yin Deficiency
Yunxiao GAO ; Qiuyan ZHANG ; Juqin PENG ; Hao GUO ; Xiaoxiao CHEN ; Wei HAO ; Longxiao HU ; Yali SHI ; Junguo REN ; Jianxun LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(4):134-142
ObjectiveTo explore the establishment and evaluation methods of the rat model of acute myocardial infarction (AMI) in coronary heart disease with the syndrome of Qi and Yin deficiency by sleep deprivation (SD) combined with isoproterenol (ISO) and preliminarily explore its biological basis. MethodForty SD rats were assigned into normal (no treatment), SD (treatment in modified multi-platform water environment for 96 h), ISO (subcutaneous injection of ISO at 100 mg·kg-1 once every other day for a total of 2 times), and SD+ISO (injection of 100 mg·kg-1 ISO after SD for 72 h and 96 h) groups. The cardiac function was detected by small animal echocardiography. The serum levels of creatine kinase (CK), creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), and cardiac troponin T (cTnT) were measured by biochemical methods. The pathological changes of the myocardial tissue were observed by hematoxylin-eosin staining. The general state, body weight, grip strength, body temperature, behaviors in open field test, serum levels of cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), cAMP/cGMP ratio, red (R), green (G), blue (B) values of the tongue surface, and pulse amplitude were observed and measured to evaluate the modeling results. Enzyme-linked immunosorbent assay was employed to determine the serum levels of interleukin-18 (IL-18), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), malondialdehyde (MDA), corticotropin-releasing factor (CRF), adrenocorticotropic hormone (ACTH), triiodothyronine (T3), tetraiodothyronine (T4), cluster of differentiation 4 (CD4), and cluster of differentiation 8 (CD8). ResultIn terms of disease indicators, the ISO and SD+ISO groups had lower cardiac function indicators than the normal group (P<0.01). The levels of CK, CM-MB, LDH and cTnT elevated in each model group compared with the normal group (P<0.01). The pathological changes of myocardial tissue were obvious in the ISO and SD+ISO groups. In terms of syndrome indicators, compared with the normal group, the SD and SD+ISO groups showed decreased body weight at each time point (P<0.01), and the ISO group showed decreased body weight at the time points of 48 h and 72 h (P<0.05, P<0.01). The paw temperature and rectal temperature increased in the SD group (P<0.01). The model groups showed weakened grasp strength, lowered R, G, and B values of the tongue surface (P<0.01), prolonged immobility time (P<0.01), reduced total distance and number of entering the central area (P<0.01), decreased average speed (P<0.05, P<0.01), and increased cAMP and cGMP (P<0.05, P<0.01). The cAMP/cGMP ratio was increased in the SD+ISO group (P<0.01), and the pulse amplitude was decreased in the SD and SD+ISO groups (P<0.01). In terms of serological indicators,compared with the normal group, the levels of IL-18, TNF-α, SOD and MDA were significantly increased in the ISO and SD+ISO groups (P<0.01), the CRF, ACTH, CORT, T3, T4, CD4 and CD8 in the model groups were increased (P<0.05, P<0.01). ConclusionSleep deprivation for 96 h combined with high-dose ISO can successfully establish a rat model of acute myocardial infarction in coronary heart disease with the syndrome of Qi and Yin deficiency. The model evaluation system can be built with disease indicators of western medicine, histopathological indicators, macroscopic indicators of traditional Chinese medicine, and serological indicators.
3.Study on Metabonomics of Myocardial Tissue of Rat Model with Coronary Heart Disease of Heart Blood Stasis Syndrome
Jing LI ; Zhihua GUO ; Jianhe LIU ; Senjie ZHONG ; Huifang KUANG ; Yang YANG ; Yi LIU ; Qiuyan ZHANG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(3):119-126
Objective To investigate the biological basis of disease and syndrome by studying the spectrum of myocardial tissue metabolites in the rat model of coronary heart disease with heart blood stasis syndrome.Methods SD rats were randomly divided into sham-operation group and model group.The left anterior descending coronary artery was ligated to prepare the rat model of coronary heart disease with heart blood stasis syndrome.The general condition was observed,and the tongue chromaticity,electrocardiogram,cardiac function were detected.HE staining and transmission electron microscopy were used to observe myocardial tissue morphology and ultrastructure.UPLC-MS technology was used to investigate the differential metabolites in rat myocardial tissue,and enrichment analysis was conducted on metabolic pathways.Results Compared with the sham-operation group,the tongue chromaticity R,G,B values of model group rats were significantly reduced(P<0.05),ECG heart rate and ST segment elevation amplitude significantly increased(P<0.05),LVEF and LVFS significantly decreased,and LVIDs and LVIDd significantly increased(P<0.05).Myocardial tissue pathology revealed that the structure was blurred,inflammatory cells infiltrated,mitochondria swelled,ruptured,and dissolved,and crista structure fracture decreased.A total of 29 potential biomarkers with significant differences between the sham-operation group and the model group were identified in metabolomics(7 upregulated and 22 downregulated),with the majority of 10 pathways enriched in thiamine metabolism,arginine biosynthesis,purine metabolism,aminoacyl-tRNA biosynthesis,alanine,aspartate and glutamate metabolism,pentose and glucuronate interconversions,glycolysis/gluconeogenesis,valine,leucine and isoleucine degradation,TCA cycle,pyruvate metabolism.Conclusion Ligation of the left anterior descending coronary artery can mimic the pathological process of coronary heart disease with blood stasis syndrome in a good way,and its pathological mechanism involves the disruption of multi-level metabolic networks such as glucose metabolism,mitochondrial energy metabolism,amino acid metabolism,protein biosynthesis,and purine metabolism.
4.Mechanism of Glycyrrhizae Radix et Rhizoma Alleviating Tripterygium wilfordii Polyglycoside Tablets-induced Liver Injury
Minghong ZHAO ; Tianming LU ; Li LIU ; Qixin WANG ; Tong YANG ; Na LIN ; Chong QIU ; Tianyu ZHONG ; Qiuyan GUO ; Jigang WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(5):24-31
ObjectiveTo investigate the protective effect of cytochrome P4502D6 (CYP2D6) and cytochrome P4503A4 (CYP3A4), key enzymes of drug metabolism in liver, on acute liver injury in water extract of Glycyrrhizae Radix et Rhizoma (WEOGRR). MethodHealthy male Kunming mice were divided into normal group, model group, WEOGRR low-, medium- and high-dose groups (5, 10, 15 g·kg-1·d-1) and positive drug group (diammonium glycyrrhizinate, 75 mg·kg-1·d-1), with 10 in each group. One week after preventive administration, acute liver injury model was induced by single intragastric administration of 270 mg·kg-1 Tripterygium Glycosides tablets, and samples were collected after 18 h. The pathological changes of liver were observed by hematoxylin-eosin (HE) staining. Serum liver function indexes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptadase (γ-GT), alkaline phosphatase (ALP), and total bilirubin (TBIL) as well as the levels of oxidative stress indexes including malondialdehyde (MDA) and superoxide dismutase (SOD) in hepatocytes were determined by biochemical method. Real-time polymerase chain reaction (Real-time PCR) and Western blot were performed to detect the mRNA and protein expression levels of CYP2D6 and CYP3A4, respectively. ResultCompared with normal group, model group had significant hepatocyte swelling and inflammatory cell infiltration (P<0.01), increased AST, ALT, γ-GT, ALP and TBIL (P<0.05), elevated MDA and decreased SOD (P<0.01) as well as down-regulated mRNA and protein expression levels of CYP2D6 and CYP3A4 (P<0.05). Compared with the model group, the normal group had intact liver structure without obvious abnormality, and the WEOGRR groups and positive drug group presented alleviated hepatocyte swelling and inflammatory cell infiltration (P<0.01), reduced AST, ALT, γ-GT, ALP and TBIL (P<0.01), lowered MDA and increased SOD (P<0.01) as well as up-regulated expression levels of CYP2D6 and CYP3A4 (P<0.01). ConclusionThe protective effect of WEOGRR on acute liver injury induced by Tripterygium glycosides tablets may be related to reducing the contents of AST, ALT, γ-GT, ALP and TBIL in serum, inhibiting MDA and increasing the activity of SOD in liver cells, and enhancing the activities of CYP2D6 and CYP3A4, thus accelerating the metabolism of toxic substances.
5.Mechanism of Honghua Oral Liquid in Alleviating Neuropathic Pain
Qiuyan GUO ; Minghong ZHAO ; Tianming LU ; Fei XIA ; Ying ZHANG ; Hongbing ZHANG ; Xiaoru ZHAI ; Qian YANG ; Yongdong LI ; Jin LI ; Xin LI ; Shuo SHEN ; Liwei GU ; Maobo DU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(6):222-230
ObjectiveTo investigate the pharmacodynamic characteristics and explore the molecular mechanism of Honghua oral liquid (HOL) in relieving neuropathic pain (NP). MethodHealthy male SD rats were randomly assigned into sham group, model group, low-, medium-, high-dose (0.5, 1.0, 2.0 mL·kg-1·d-1, respectively) HOL groups, and a positive drug (pregabalin, 25 mg·kg-1·d-1) group, with 6 rats in each group. Spinal nerve ligation (SNL) of L5 was conducted in other groups except the sham group. Drug administration was performed 3 days after the SNL surgery for 2 consecutive weeks, and samples were collected after the end of the administration. During the treatment period, the mechanical pain threshold and cold pain threshold were determined to measure the pain-relieving effect of HOL. Transcriptome sequencing was performed on hippocampal tissue samples from the sham, model, and high-dose HOL groups, and differentially expressed genes between the sham group and the model group as well as the model group and HOL high-dose group were obtained. After pathway enrichment analysis, we selected the targets which were closely related to neuroinflammation for validation, and predicted the specific binding sites of the major active components in HOL with the targets through molecular docking. In addition, the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were determined by enzyme-linked immunosorbent assay (ELISA) to evaluate the effect of HOL on neuroinflammation in NP rats. ResultCompared with the sham group, SNL decreased the mechanical pain threshold and cold pain threshold (P<0.05). Compared with the model group, HOL recovered the mechanical pain threshold and cold pain threshold (P<0.05). The transcriptome data showed that 376 differentially expressed genes (DEGs) were identified between the model group and the sham group, including 124 upregulated genes and 252 downregulated genes, and 194 DEGs between the model group and the high-dose HOL group, including 33 upregulated genes and 161 downregulated genes. Among them, insulin-like growth factor 1(IGF1), matrix metallopeptidase-2 (MMP-2), matrix metallopeptidase-14 (MMP-14), erb-B2 receptor tyrosine kinase 2 (ERBB2), and integrin subunit alpha 5 (ITGA5) associated with NP were selected for further validation. The Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) results showed that compared with the sham group, the modeling up-gurelated the mRNA levels of the above five molecules in the hippocampus (P<0.01). Compared with model group, HOL down-regulated the mRNA levels of these molecules (P<0.01). The molecular docking results showed that the main active components of safflower, hydroxysafflor yellow A, kaempferol, and quercetin, formed stable hydrogen bonds with the amino acid residues of IGF1, MMP-2, MMP-14, ERBB2, and ITGA5. The enzyme-linked immunosorbent assay(ELISA) results showed that compared with those in the sham group, the serum levels of TNF-α and IL-10 were out of balance in the model rats (P<0.01). Compared with the model group, HOL lowered the level of the pro-inflammatory cytokine TNF-α (P<0.01) and elevated that of the anti-inflammatory cytokine IL-10 (P<0.05). ConclusionHOL exerts analgesic effect on SNL rats by inhibiting neuroinflammation.
6.Pathogenesis of Metabolic Remodeling of Energy Substrate Based on Theory of Deficient Qi Stagnation and Progress of Chinese Medicine Intervention
Jing LI ; Senjie ZHONG ; Huifang KUANG ; Yang YANG ; Yi LIU ; Shuchun HUANG ; Zhihua GUO ; Qiuyan ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(17):195-202
In the case of cardiac dysfunction, energy metabolism changes and the metabolism of myocardial substrates is reconstructed, as manifested by variation in the selection and utilization of energy substrates such as fatty acids and glucose. Persistent metabolic disorders of substrates will decrease energy supply, thus resulting in the occurrence and development of heart failure. Metabolic remodeling of substrate is resulted from the decline of visceral function and the accumulation of pathological products. Deficient Qi stagnation is the core pathogenesis. Deficient Qi (heart Qi deficiency, insufficient energy) is the root cause, which exists in the whole disease course. Stagnation (phlegm, blood stasis, fluid, lipid toxic products, lactic acid, etc.) is the symptom, which evidences the aggravation of the disease. Deficient Qi and stagnation are intertwined and causal, which form a spiral vicious circle. The typical syndrome is excess resulted from deficiency and deficiency-excess in complexity. The treatment principle is reinforcing healthy Qi and tonifying deficiency, dredging and removing pathogen. At the early stage, the method of reinforcing healthy Qi and tonifying deficiency (benefiting Qi) should be used, and the method of dredging and removing pathogen (activating blood) can be applied according to the conditions of patients. At the middle and late stages, both reinforcing healthy Qi and tonifying deficiency (benefiting Qi and warming Yang) and dredging and removing pathogen (activating blood, resolving stasis, and excreting water) should be emphasized. Chinese medicine can be applied according to the pathogenesis, thereby promoting the utilization of fatty acids, glucose, and other substrates and reducing the accumulation of toxic products derived from metabolic remodeling of substrate. Thus, both the root cause and symptoms can be alleviated, further improving cardiac energy metabolism and heart function.
7.Single-cell transcriptome analysis reveals the regulatory effects of artesunate on splenic immune cells in polymicrobial sepsis
Jiayun CHEN ; Xueling HE ; Yunmeng BAI ; Jing LIU ; Kwan-Yin WONG ; Lulin XIE ; Qian ZHANG ; Piao LUO ; Peng GAO ; Liwei GU ; Qiuyan GUO ; Guangqing CHENG ; Chen WANG ; Jigang WANG
Journal of Pharmaceutical Analysis 2023;13(7):817-829
Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomod-ulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various im-mune cells remain limited.This study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental validations.The scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during sepsis.ART could restore neutrophils'chemotaxis and immune function in the septic spleen.It inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during sepsis.ART also promoted the differentiation and activity of splenic B cells in mice with sepsis.These results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the host.Overall,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.
8.Single-cell transcriptome analysis uncovers underlying mechanisms of acute liver injury induced by tripterygium glycosides tablet in mice
Qiuyan GUO ; Jiangpeng WU ; Qixin WANG ; Yuwen HUANG ; Lin CHEN ; Jie GONG ; Maobo DU ; Guangqing CHENG ; Tianming LU ; Minghong ZHAO ; Yuan ZHAO ; Chong QIU ; Fei XIA ; Junzhe ZHANG ; Jiayun CHEN ; Feng QIU ; Jigang WANG
Journal of Pharmaceutical Analysis 2023;13(8):908-925
Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40%of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated he-patic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and ther-apeutic targets for liver protection.
9.Discovery and repurposing of artemisinin.
Qiaoli SHI ; Fei XIA ; Qixin WANG ; Fulong LIAO ; Qiuyan GUO ; Chengchao XU ; Jigang WANG
Frontiers of Medicine 2022;16(1):1-9
Malaria is an ancient infectious disease that threatens millions of lives globally even today. The discovery of artemisinin, inspired by traditional Chinese medicine (TCM), has brought in a paradigm shift and been recognized as the "best hope for the treatment of malaria" by World Health Organization. With its high potency and low toxicity, the wide use of artemisinin effectively treats the otherwise drug-resistant parasites and helps many countries, including China, to eventually eradicate malaria. Here, we will first review the initial discovery of artemisinin, an extraordinary journey that was in stark contrast with many drugs in western medicine. We will then discuss how artemisinin and its derivatives could be repurposed to treat cancer, inflammation, immunoregulation-related diseases, and COVID-19. Finally, we will discuss the implications of the "artemisinin story" and how that can better guide the development of TCM today. We believe that artemisinin is just a starting point and TCM will play an even bigger role in healthcare in the 21st century.
Artemisinins/therapeutic use*
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COVID-19/drug therapy*
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Drug Repositioning
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Humans
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Medicine, Chinese Traditional
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Neoplasms/drug therapy*
10.Application value of imaging examinations in the diagnosis of small hepatocellular carcinoma
Qiuyan WU ; Juan LIU ; Chongshuang YANG ; Chunlin TANG ; Ping CHEN ; Kaixuan CHEN ; Li LIU ; Yangmei ZENG ; Yanli GUO
Chinese Journal of Digestive Surgery 2022;21(4):543-550
Objective:To investigate the application value of contrast-enhanced ultra-sound, enhanced computed tomography (CT) and enhanced magnetic resonance imaging (MRI) in the diagnosis of small hepatocellular carcinoma.Methods:The clinical diagnositic trial was con-ducted. The clinicopathological data of 145 patients with small hepatocellular carcinoma who were admitted to the First Affiliated Hospital of Amy Medical University from January 2019 to June 2021 were collected. There were 121 males and 24 females, aged from 26 to 78 years, with a median age of 54 years. All patients were examined with contrast-enhanced ultrasound, enhanced CT and enhanced MRI, and underwent surgical resection of liver lesions within one month. Observation indicators: (1) postoperative histopathological examinations of patients with small hepatocellular carcinoma; (2) examination of small hepatocellular carcinoma by contrast-enhanced ultrasound, enhanced CT and enhanced MRI; (3) imaging features of small hepatocellular carcinoma in the contrast-enhanced ultrasound, enhanced CT and enhanced MRI; (4) enhancement mode distribution of small hepatocellular carcinoma in the arterial, portal and delayed phases of contrast-enhanced ultrasound, enhanced CT and enhanced MRI; (5) the efficacy of contrast-enhanced ultrasound, enhanced CT and enhanced MRI in the diagnosis of small hepatocellular carcinoma. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the Cochran′s Q test or the chi-square test. The sensitivity, specificity and accuracy were used to analyze the efficacy of contrast-enhanced ultrasound, enhanced CT and enhanced MRI in the diagnosis of small hepatocellular carcinoma. Results:(1) Postoperative histopathological examinations of patients with small hepatocellular carcinoma. There were 154 lesions detected in the postoperative histopathological examinations for the 145 small hepatocellular carcinoma patients, with the tumor diameter as (2.2±0.6)cm. (2) Examination of small hepatocellular carcinoma by contrast-enhanced ultrasound, enhanced CT and enhanced MRI. There were 153, 154 and 154 lesions detected in contrast-enhanced ultrasound, enhanced CT and enhanced MRI for the 145 patients with small hepatocellular carcinoma, respectively, with the detection rate as 99.35%(153/154), 100.00%(154/154) and 100.00%(154/154), showing no significant difference among the 3 imaging examination methods ( Q=2.00, P>0.05). (3) Imaging features of small hepatocellular carcinoma in the contrast-enhanced ultrasound, enhanced CT and enhanced MRI. Of the 153 lesions reported in contrast-enhanced ultrasound for patients with small hepatocellular carcinoma, 140 lesions showed "fast-in and fast-out" enhancement, 12 lesions showed "fast-in and slow-out" enhancement and 1 lesion showed isoenhancement in arterial phases and hypoenhancement in portal and delayed phase. Of the 154 lesions reported in enhanced CT for patients with small hepatocellular carcinoma, 112 lesions showed "fast-in and fast-out" enhancement, 13 lesions showed "fast-in and slow-out" enhancement, 14 lesions showed isoenhancement in arterial phase and hypoenhancement in portal and delayed phases, 5 lesions showed rim-like hyperenhancement in arterial phase and hypoenhancement in portal and delayed phases, 5 lesions showed hypoenhancement in the three phases, 3 lesions showed hyperenhancement in the three phases, 1 lesion showed isoenhancement in the three phases and 1 lesion showed isoenhancement in arterial and portal phases and hypoenhancement in delayed phase. Of the 154 lesions reported in enhanced MRI for patients with small hepatocellular carcinoma, 134 lesions showed "fast-in and fast-out" enhancement, 1 lesion showed "fast-in and slow-out" enhancement, 8 lesions showed isoenhancement in arterial phase and hypoenhance-ment in portal and delayed phases, 5 lesions showed rim-like hyperenhancement in arterial phase and hypoenhancement in portal and delay phases, 2 lesions showed rim-like hyperenhancement in the three phases, 1 lesion showed hyperenhancement in the three phases, 1 lesion showed hypoenhancement in the three phases, 1 lesion showed isoenhancement in arterial and portal phases and hypoenhancement in delayed late phase, 1 lesion showed edge delay enhancement in the three phases. (4) Enhancement mode distribution of small hepatocellular carcinoma in the arterial, portal and delayed phases of contrast-enhanced ultrasound, enhanced CT and enhanced MRI. Of the 153 lesions reported in contrast-enhanced ultrasound for patients with small hepatocellular carcinoma, there were 152 lesions with hyperenhancement and 1 lesion with iso or hypoenhance-ment in the arterial phase, there were 55 lesions with hyper or isoenhancement and 98 lesions with hypoenhancement in the portal venous phase, there were 12 lesions with hyper or isoenhancement and 141 lesions with hypoenhancement in the delayed phase. Of the 154 lesions reported in enhanced CT for patients with small hepatocellular carcinoma, there were 133 lesions with hyperen-hancement signal and 21 lesions with iso or hypoenhancement in the arterial phase, there were 53 lesions with hyper or isoenhancement and 101 lesions with hypoenhancement in the portal phase, there were 17 lesions with hyper or isoenhancement and 137 lesions with hypoenhancement in the delayed phase. Of the 154 lesions reported in enhanced MRI for patients with small hepatocellular carcinoma, there were 143 lesions with hyperenhancement and 11 lesions with iso or hypoenhance-ment in the arterial phase, there were 29 lesions with hyper or isoenhancement and 125 lesions with hypoenhancement in the portal phase, there were 5 lesions with hyper or isoenhancement and 149 lesions with hypoenhancement in the delayed phase. There were significant differences in the enhancement mode distribution of lesions in the arterial, portal and delayed phases among contrast-enhanced ultrasound, enhanced CT and enhanced MRI ( χ2=19.47, 13.21, 6.92, P<0.05). (5) The efficacy of contrast-enhanced ultrasound, enhanced CT and enhanced MRI in the diagnosis of small hepatocellular carcinoma. Of the 153 lesions reported in contrast-enhanced ultrasound for patients with small hepatocellular carcinoma, there were 3 lesions misdiagnosed according to the postoperative histopathological examinations. Of the 154 lesions reported in enhanced CT and enhanced MRI for patients with small hepatocellular carcinoma, there were 7 lesions and 2 lesions misdiagnosed according to the postoperative histopathological examinations, respectively. Lesions misdiagnosed in one imaging examination method were correctly diagnosed in the other two imaging examination methods. The sensitivity, specificity, accuracy were 97.4%, 63.0%, 92.3% for contrast-enhanced ultrasound in the diagnosis of small hepatocellular carcinoma. The above indica-tors were 95.5%, 63.0%, 90.6% for enhanced CT and 98.7%, 63.0%, 93.4% for enhanced MRI in the diagnosis of small hepatocellular carcinoma. There was no significant difference in the sensitivity and accuracy among the 3 imaging examination methods ( Q=2.92, 0.00, 1.81, P>0.05). Conclusion:Contrast-enhanced ultrasound, enhanced CT and enhanced MRI all have good diagnostic value in diagnosis of small hepatocellular carcinoma, and they complement each other.

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