1.Dihuang Yinzi Improves Cognitive Function of Mouse Model of Learning and Memory Impairments by Regulating Synaptic Plasticity via SIRT2
Wenting WANG ; Yangjing HAO ; Wenna SU ; Qinqing LI ; Shifeng CHU ; Junlong ZHANG ; Wenbin HE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):9-17
ObjectiveTo investigate the effects of Dihuang Yinzi on the cognitive function in the mouse model of learning and memory impairments induced by scopolamine (SCOP) and explore the treatment mechanism. MethodsA mouse model of learning and memory impairment was induced by intraperitoneal injection of SCOP. Sixty male C57BL/6J mice were randomized into six groups: control (0.9% NaCl, n=10), model (SCOP 1 mg·kg-1·d-1, n=10), low-, medium-, and high-dose Dihuang Yinzi (SCOP 1 mg·kg-1·d-1 + Dihuang Yinzi 5.5, 11.0, and 22.0 g·kg-1·d-1, n=10), and donepezil (SCOP 1 mg·kg-1·d-1 + donepezil 0.84 mg·kg-1·d-1, n=10). Mice were administrated with corresponding drugs for 6 weeks. Modeling started in the 4th week, and mice in other groups except the control group were injected with SCOP intraperitoneally 40 min after daily gavage. Behavioral testing began in the 5th week, 30 min after modeling each day. The Morris water maze and novel object recognition tests were carried out to evaluate the spatial learning and memory function of mice. Nissl staining was employed to observe the survival of neurons and Nissl bodies in the hippocampal CA1 region. Western blot was employed to determine the protein levels of silent information regulator 2 (SIRT2), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor 1 (GluA1), protein kinase A (PKA), cAMP response element-binding protein (CREB), phosphorylated-CREB (p-CREB), postsynaptic density protein 95 (PSD95), growth-associated protein-43 (GAP-43), and synaptophysin (SYN) in the hippocampus. Immunofluorescence was used to detect the expression of doublecortin (DCX) in the hippocampal dentate gyrus (DG) region. ResultsCompared with the control group, the model group showed impaired learning and memory (P<0.01), obvious neuronal damage in the hippocampal CA1 region, a reduction in neuron survival (P<0.01), a decrease in DCX expression in the hippocampal DG region (P<0.01), down-regulated proteins levels of GluA1, PKA, p-CREB/CREB, PSD95, SYN, and GAP-43 in the hippocampal tissue (P<0.05, P<0.01), and an up-regulated protein level of SIRT2 (P<0.01). Compared with the model group, the medium- and high-dose Dihuang Yinzi groups and the donepezil group showed improvements in learning and memory (P<0.05, P<0.01), while the low-, medium-, and high-dose Dihuang Yinzi groups and the donepezil group had increased neuron survival (P<0.05, P<0.01). The medium-dose Dihuang Yinzi group and the donepezil group showed increased DCX expression (P<0.05, P<0.01). The medium- and high-dose Dihuang Yinzi groups and the donepezil group showed up-regulation in the protein levels of GluA1, PKA, p-CREB/CREB, PSD95, SYN, and GAP-43 (P<0.05, P<0.01) and down-regulation in the protein level of SIRT2 (P<0.01). ConclusionDihuang Yinzi can improve the cognitive function in the mouse model of learning and memory impairments induced by SCOP by inhibiting the upregulation of SIRT2, activating the PKA/CREB signaling pathway, improving synaptic plasticity, and reducing hippocampal neuronal damage.
2.Updates and amendments of the Chinese Pharmacopoeia 2025 Edition (Volume Ⅰ)
LI Hao ; SHEN Mingrui ; ZHANG Pang ; ZHAI Weimin ; NI Long ; HAO Bo ; ZHAO Yuxin ; HE Yi ; MA Shuangcheng ; SHU Rong
Drug Standards of China 2025;26(1):017-022
The Chinese Pharmacopoeia is the legal technical standard which should be followed during the research, production, use, and administration of drugs. At present, the new edition of the Chinese Pharmacopoeia is planned to be promulgated and implemented. This article summarizes and analyzes the main characteristics and the content of updates and amendments of the Chinese Pharmacopoeia 2025 Edition(Volume Ⅰ), to provide a reference for the correct understanding and accurate implementation the new edition of the pharmacopoeia.
3.Gut microbiota and osteoporotic fractures
Wensheng ZHAO ; Xiaolin LI ; Changhua PENG ; Jia DENG ; Hao SHENG ; Hongwei CHEN ; Chaoju ZHANG ; Chuan HE
Chinese Journal of Tissue Engineering Research 2025;29(6):1296-1304
BACKGROUND:Osteoporotic fracture is the most serious complication of osteoporosis.Previous studies have demonstrated that gut microbiota has a regulatory effect on skeletal tissue and that gut microbiota has an important relationship with osteoporotic fracture,but the causal relationship between the two is unclear. OBJECTIVE:To explore the causal relationship between gut microbiota and osteoporotic fractures using Mendelian randomization method. METHODS:The genome-wide association study(GWAS)datasets of gut microbiota and osteoporotic fracture were obtained from the IEU Open GWAS database and the Finnish database R9,respectively.Using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,Mendelian randomization analyses with random-effects inverse variance weighted,MR-Egger regression,weighted median,simple model,and weighted model methods were performed to assess whether there is a causal relationship between gut microbiota and osteoporotic fracture.Sensitivity analyses were performed to test the reliability and robustness of the results.Reverse Mendelian randomization analyses were performed to further validate the causal relationship identified in the forward Mendelian randomization analyses. RESULTS AND CONCLUSION:The results of this Mendelian randomization analysis indicated a causal relationship between gut microbiota and osteoporotic fracture.Elevated abundance of Actinomycetales[odds ratio(OR)=1.562,95%confidence interval(CI):1.027-2.375,P=0.037),Actinomycetaceae(OR=1.561,95%CI:1.027-2.374,P=0.037),Actinomyces(OR=1.544,95%CI:1.130-2.110,P=0.006),Butyricicoccus(OR=1.781,95%CI:1.194-2.657,P=0.005),Coprococcus 2(OR=1.550,95%CI:1.068-2.251,P=0.021),Family ⅩⅢ UCG-001(OR=1.473,95%CI:1.001-2.168,P=0.049),Methanobrevibacter(OR=1.274,95%CI:1.001-1.621,P=0.049),and Roseburia(OR=1.429,95%CI:1.015-2.013,P=0.041)would increase the risk of osteoporotic fractures in patients.Elevated abundance of Bacteroidia(OR=0.660,95%CI:0.455-0.959,P=0.029),Bacteroidales(OR=0.660,95%CI:0.455-0.959,P=0.029),Christensenellacea(OR=0.725,95%CI:0.529-0.995,P=0.047),Ruminococcaceae(OR=0.643,95%CI:0.443-0.933,P=0.020),Enterorhabdus(OR=0.558,95%CI:0.395-0.788,P=0.001),Eubacterium rectale group(OR=0.631,95%CI:0.435-0.916,P=0.016),Lachnospiraceae UCG008(OR=0.738,95%CI:0.546-0.998,P=0.048),and Ruminiclostridium 9(OR=0.492,95%CI:0.324-0.746,P=0.001)would reduce the risk of osteoporotic fractures in patients.We identified 16 gut microbiota associated with osteoporotic fracture by the Mendelian randomization method.That is,using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,eight gut microbiota showed positive causal associations with osteoporotic fracture and another eight gut microbiota showed negative causal associations with osteoporotic fracture.The results of this study not only identify new biomarkers for the early prediction of osteoporotic fracture and potential therapeutic targets in clinical practice,but also provide an experimental basis and theoretical basis for the study of improving the occurrence and prognosis of osteoporotic fracture through gut microbiota in bone tissue engineering.
4.Diagnosis and treatment strategies of respiratory viral infection in transplant recipients
Chunrong JU ; Chuangli HAO ; Wujun XUE ; Jianxing HE
Organ Transplantation 2025;16(2):220-228
Viral infection has always been a significant challenge to human health. Transplant recipients, including those who have undergone solid organ transplantation and allogeneic hematopoietic stem cell transplantation, are at high risk of viral infection due to their weak immune function under immunosuppressive therapy. Unlike the general population, transplant recipients are prone to pneumonia and even severe pneumonia after respiratory viral infection, which requires close attention from clinicians. Therefore, this article reviews the clinical characteristics and special management of viral infection in this population, focusing on the epidemiological features of common respiratory viral infection in transplant recipients, early diagnosis and intervention after infection, severe warning signs and drug treatment strategies, for the reference of clinical colleagues.
5.The effect and mechanism of Huangkui capsule pretreatment of human umbilical cord mesenchymal stem cell-derived exosomes on improving renal ischemia-reperfusion injury
Yawei YAO ; Jiahui HE ; Hao WANG ; Yutong WANG ; Ruiyan WANG ; Xingyu WAN ; Yujia LIU ; Xinghua LÜ
Organ Transplantation 2025;16(2):237-245
Objective To explore the effects and mechanisms of human umbilical cord mesenchymal stem cell (HUC-MSC)-derived exosomes (Exo) pretreated with Huangkui capsules on renal ischemia-reperfusion injury (IRI). Methods HUC-MSCs were cultured in media containing different concentrations of Huangkui capsules for 24 hours to determine cell viability and select an appropriate concentration for subsequent experiments. HUC-MSCs were pretreated with 50 μg/mL Huangkui capsules for 24 hours, and Exo were extracted using an exosome extraction kit. The morphology was observed under a transmission electron microscope, particle size was measured by nanoparticle tracking analysis, and the expression of exosomal membrane surface marker proteins was detected by Western blot. Human renal tubular epithelial cells (HK-2 cells) were randomly divided into hypoxia/reoxygenation group (M group), hypoxia/reoxygenation + Exo group (E group), and hypoxia/reoxygenation + Huangkui capsules pretreated Exo group (H group). Western blotting was used to measure the expression of endoplasmic reticulum stress (ERS)-related proteins, and real-time fluorescent quantitative reverse transcription polymerase chain reaction was used to measure the expression of ERS-related gene messenger RNA (mRNA). Mice were randomly divided into sham operation group (Sham group), ischemia-reperfusion group (I/R group), ischemia-reperfusion + Exo group (E group), and ischemia-reperfusion + Huangkui capsules pretreated Exo group (H group). Renal histological assessment, serum creatinine (Scr), blood urea nitrogen (BUN) measurement and inflammatory factor detection were performed 24 hours later. Results Both Exo and Huangkui capsules prereated Exo had a bilayer membrane structure and a cup-shaped morphology; their average particle sizes were 116.8 nm and 81.3 nm, respectively. Both expressed CD9, CD63, TSG101. Compared with the M group, the E group had decreased relative expression of transcription factor 6 (ATF6) and protein kinase R-like endoplasmic reticulum kinase (PERK) proteins, increased mRNA relative expression, increased relative expression of C/EBP homologous protein (CHOP) protein, and decreased mRNA relative expression. Compared with the E group, the H group had decreased relative expression of ATF6, PERK, CHOP proteins, and decreased mRNA relative expression of ATF6 and PERK (all P<0.05). Animal experimental results showed that compared with the Sham group, the I/R group had increased renal tubular injury scores, Scr, BUN, interleukin (IL)-1β, IL-10, IL-18, tumor necrosis factor (TNF)-α levels. Compared with the I/R group, the E and H groups had decreased renal tubular injury scores and Scr, BUN, IL-1β, IL-10, IL-18, TNF-α levels. Compared with the E group, the H group had decreased renal tubular injury scores and Scr, BUN, IL-1β, IL-10, IL-18, TNF-α levels (all P<0.05). Conclusions Huangkui capsules pretreatment HUC-MSC-derived Exo may alleviate renal IRI by inhibiting ERS.
6.Action Mechanism of Resolving Dampness and Phlegm of Pinelliae Rhizoma Praeparatum Based on Interconnection Between Lung and Large Intestine
Xingbao TAO ; Chentao ZHAO ; Xiaofu ZHU ; Hao WU ; Jun HE ; Weiguo CAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):122-131
ObjectiveTo investigate the effects of Pinelliae Rhizoma Praeparatum (PRP) on lung tissue, gut microbiota, and short-chain fatty acid (SCFA) metabolism in a model of mice with cold fluid retention in the lung and explore its mechanism of action in resolving dampness and phlegm based on the interconnection between the lung and large intestine. MethodsFifty female ICR mice were randomly divided into a normal group, model group, positive control group (Xiaoqinglong granules, 6.5 g·kg-1), and high-dose and low-dose PRP decoction groups (3.0, 1.5 g·kg-1), with 10 mice in each group. A model of mice with cold fluid retention in the lung was established using ovalbumin (OVA) sensitization combined with cold-water immersion. Drug interventions were conducted from day 18 to day 33 for 15 consecutive days. The airway resistance value of the mice was measured using a non-invasive pulmonary function analyzer. Phlegm-resolving effects were evaluated via a microplate reader. Eosinophil and neutrophil counts in bronchoalveolar lavage fluid (BALF) were analyzed using an automated hematology analyzer. Serum levels of total immunoglobulin E (IgE), interferon-γ (IFN-γ), interleukin-4 (IL-4), and BALF levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) were quantified by enzyme-linked immunosorbent assay (ELISA). Lung histopathology was assessed using hematoxylin-eosin (HE) staining. Immunohistochemistry (IHC) was employed to detect mucin 5AC (MUC5AC) and aquaporin 5 (AQP5) protein expression in lung tissue. Gut microbiota composition was analyzed via agarose gel electrophoresis, and fecal SCFA levels were measured by gas chromatography-mass spectrometry (GC-MS). ResultsCompared with the normal group, the model group exhibited significantly increased airway resistance value (RI) (P<0.05), elevated eosinophil and neutrophil counts and IL-6 and IL-8 levels in BALF (P<0.05), increased serum IgE and IL-4 levels (P<0.05), with reduced IFN-γ levels (P<0.05). It also showed thickened bronchial walls, widened alveolar septa, narrowed lumens, and mucus plugs in lung tissue, upregulated MUC5AC protein expression and downregulated AQP5 protein expression (P<0.05), decreased relative abundance of beneficial gut microbiota (Firmicutes, Clostridia, Clostridiales, Lactobacillaceae, and Lactobacillus), and increased abundance of harmful microbiota (Bacteroidetes, Bacteroidia, Bacteroidales, Muribaculaceae, and Muribaculum). In addition, the model group presented reduced fecal SCFA levels (acetate, propionate, and butyrate) (P<0.05). After the intervention of PRP decoction, compared to the model group, all drug administration groups showed decreased RI (P<0.05), increased phenol red excretion, declined eosinophil and neutrophil counts and IL-6, IL-8, IgE, and IL-4 levels (P<0.05), and improved IFN-γ levels (P<0.05) and lung pathology improved. The MUC5AC protein expression decreased (P<0.05), and the AQP5 protein expression increased (P<0.05). The disorder of gut microbiota was improved, and the diversity of gut microbiota was restored, with a significantly increased relative abundance ratio of beneficial microbiota (P<0.05) and a significantly reduced relative abundance ratio of harmful microbiota (P<0.05). The SCFA levels (acetate, propionate, and butyrate) increased (P<0.05). The efficacy indicators of serum inflammatory factors (IgE, IL-4, and IFN-γ), phlegm-resolving effect, airway resistance, total pathological score, and the protein expression of MUC5AC and AQP5 were correlated with gut microbiota and SCFAs. ConclusionPRP decoction alleviates cold-phlegm syndrome by modulating the gut-lung axis, promoting beneficial gut microbiota, enhancing SCFA production, restoring the balance of gut microbiota, and suppressing respiratory inflammation. This study provides novel insights into the TCM theory of interconnection between the lung and large intestine.
7.Action Mechanism of Resolving Dampness and Phlegm of Pinelliae Rhizoma Praeparatum Based on Interconnection Between Lung and Large Intestine
Xingbao TAO ; Chentao ZHAO ; Xiaofu ZHU ; Hao WU ; Jun HE ; Weiguo CAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):122-131
ObjectiveTo investigate the effects of Pinelliae Rhizoma Praeparatum (PRP) on lung tissue, gut microbiota, and short-chain fatty acid (SCFA) metabolism in a model of mice with cold fluid retention in the lung and explore its mechanism of action in resolving dampness and phlegm based on the interconnection between the lung and large intestine. MethodsFifty female ICR mice were randomly divided into a normal group, model group, positive control group (Xiaoqinglong granules, 6.5 g·kg-1), and high-dose and low-dose PRP decoction groups (3.0, 1.5 g·kg-1), with 10 mice in each group. A model of mice with cold fluid retention in the lung was established using ovalbumin (OVA) sensitization combined with cold-water immersion. Drug interventions were conducted from day 18 to day 33 for 15 consecutive days. The airway resistance value of the mice was measured using a non-invasive pulmonary function analyzer. Phlegm-resolving effects were evaluated via a microplate reader. Eosinophil and neutrophil counts in bronchoalveolar lavage fluid (BALF) were analyzed using an automated hematology analyzer. Serum levels of total immunoglobulin E (IgE), interferon-γ (IFN-γ), interleukin-4 (IL-4), and BALF levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) were quantified by enzyme-linked immunosorbent assay (ELISA). Lung histopathology was assessed using hematoxylin-eosin (HE) staining. Immunohistochemistry (IHC) was employed to detect mucin 5AC (MUC5AC) and aquaporin 5 (AQP5) protein expression in lung tissue. Gut microbiota composition was analyzed via agarose gel electrophoresis, and fecal SCFA levels were measured by gas chromatography-mass spectrometry (GC-MS). ResultsCompared with the normal group, the model group exhibited significantly increased airway resistance value (RI) (P<0.05), elevated eosinophil and neutrophil counts and IL-6 and IL-8 levels in BALF (P<0.05), increased serum IgE and IL-4 levels (P<0.05), with reduced IFN-γ levels (P<0.05). It also showed thickened bronchial walls, widened alveolar septa, narrowed lumens, and mucus plugs in lung tissue, upregulated MUC5AC protein expression and downregulated AQP5 protein expression (P<0.05), decreased relative abundance of beneficial gut microbiota (Firmicutes, Clostridia, Clostridiales, Lactobacillaceae, and Lactobacillus), and increased abundance of harmful microbiota (Bacteroidetes, Bacteroidia, Bacteroidales, Muribaculaceae, and Muribaculum). In addition, the model group presented reduced fecal SCFA levels (acetate, propionate, and butyrate) (P<0.05). After the intervention of PRP decoction, compared to the model group, all drug administration groups showed decreased RI (P<0.05), increased phenol red excretion, declined eosinophil and neutrophil counts and IL-6, IL-8, IgE, and IL-4 levels (P<0.05), and improved IFN-γ levels (P<0.05) and lung pathology improved. The MUC5AC protein expression decreased (P<0.05), and the AQP5 protein expression increased (P<0.05). The disorder of gut microbiota was improved, and the diversity of gut microbiota was restored, with a significantly increased relative abundance ratio of beneficial microbiota (P<0.05) and a significantly reduced relative abundance ratio of harmful microbiota (P<0.05). The SCFA levels (acetate, propionate, and butyrate) increased (P<0.05). The efficacy indicators of serum inflammatory factors (IgE, IL-4, and IFN-γ), phlegm-resolving effect, airway resistance, total pathological score, and the protein expression of MUC5AC and AQP5 were correlated with gut microbiota and SCFAs. ConclusionPRP decoction alleviates cold-phlegm syndrome by modulating the gut-lung axis, promoting beneficial gut microbiota, enhancing SCFA production, restoring the balance of gut microbiota, and suppressing respiratory inflammation. This study provides novel insights into the TCM theory of interconnection between the lung and large intestine.
8.Cost-effectiveness of Fractional Flow Reserve Versus Intravascular Ultrasound to Guide Percutaneous Coronary Intervention: Results From the FLAVOUR Study
Doyeon HWANG ; Hea-Lim KIM ; Jane KO ; HyunJin CHOI ; Hanna JEONG ; Sun-ae JANG ; Xinyang HU ; Jeehoon KANG ; Jinlong ZHANG ; Jun JIANG ; Joo-Yong HAHN ; Chang-Wook NAM ; Joon-Hyung DOH ; Bong-Ki LEE ; Weon KIM ; Jinyu HUANG ; Fan JIANG ; Hao ZHOU ; Peng CHEN ; Lijiang TANG ; Wenbing JIANG ; Xiaomin CHEN ; Wenming HE ; Sung Gyun AHN ; Ung KIM ; You-Jeong KI ; Eun-Seok SHIN ; Hyo-Soo KIM ; Seung-Jea TAHK ; JianAn WANG ; Tae-Jin LEE ; Bon-Kwon KOO ;
Korean Circulation Journal 2025;55(1):34-46
Background and Objectives:
The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea.
Methods:
A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D.
Results:
From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis.
Conclusions
Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.
9.Cost-effectiveness of Fractional Flow Reserve Versus Intravascular Ultrasound to Guide Percutaneous Coronary Intervention: Results From the FLAVOUR Study
Doyeon HWANG ; Hea-Lim KIM ; Jane KO ; HyunJin CHOI ; Hanna JEONG ; Sun-ae JANG ; Xinyang HU ; Jeehoon KANG ; Jinlong ZHANG ; Jun JIANG ; Joo-Yong HAHN ; Chang-Wook NAM ; Joon-Hyung DOH ; Bong-Ki LEE ; Weon KIM ; Jinyu HUANG ; Fan JIANG ; Hao ZHOU ; Peng CHEN ; Lijiang TANG ; Wenbing JIANG ; Xiaomin CHEN ; Wenming HE ; Sung Gyun AHN ; Ung KIM ; You-Jeong KI ; Eun-Seok SHIN ; Hyo-Soo KIM ; Seung-Jea TAHK ; JianAn WANG ; Tae-Jin LEE ; Bon-Kwon KOO ;
Korean Circulation Journal 2025;55(1):34-46
Background and Objectives:
The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea.
Methods:
A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D.
Results:
From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis.
Conclusions
Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.
10.Cost-effectiveness of Fractional Flow Reserve Versus Intravascular Ultrasound to Guide Percutaneous Coronary Intervention: Results From the FLAVOUR Study
Doyeon HWANG ; Hea-Lim KIM ; Jane KO ; HyunJin CHOI ; Hanna JEONG ; Sun-ae JANG ; Xinyang HU ; Jeehoon KANG ; Jinlong ZHANG ; Jun JIANG ; Joo-Yong HAHN ; Chang-Wook NAM ; Joon-Hyung DOH ; Bong-Ki LEE ; Weon KIM ; Jinyu HUANG ; Fan JIANG ; Hao ZHOU ; Peng CHEN ; Lijiang TANG ; Wenbing JIANG ; Xiaomin CHEN ; Wenming HE ; Sung Gyun AHN ; Ung KIM ; You-Jeong KI ; Eun-Seok SHIN ; Hyo-Soo KIM ; Seung-Jea TAHK ; JianAn WANG ; Tae-Jin LEE ; Bon-Kwon KOO ;
Korean Circulation Journal 2025;55(1):34-46
Background and Objectives:
The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea.
Methods:
A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D.
Results:
From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis.
Conclusions
Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

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