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.

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.

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.

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.

ObjectiveTo investigate the mechanism of Forsythiae Fructus-Lonicerae Japonicae Flos（FF） in the treatment of acute lung injury（ALI） by investigating the effects of FF on serum metabolomics of rats with ALI. MethodsThirty male SD rats were acclimated for 1 week， and 6 rats were randomly selected as the blank group. The other 24 rats were injected with lipopolysaccharide（LPS） solution by tracheal drip to establish an ALI model. After successful model establishment， the rats were randomly divided into the model group， the FF low-dose group（3.0 g·kg^-1）， the FF high-dose group（6.0 g·kg^-1）， and the dexamethasone group（5 mg·kg^-1）， with six rats in each group. The FF low- and high-dose groups and the dexamethasone group were received daily oral administration of the corresponding drug solution， and the blank group and the model group were gavaged with an equal amount of saline， treatment was administered continuously for 3 d. The pathological conditions of rat lung tissues were evaluated by hematoxylin-eosin（HE） staining， wet/dry mass ratio（W/D） of the lung tissues， and protein concentration in rat bronchoalveolar lavage fluid（BALF）. Metabolomic analysis of rat serum was performed by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， combined with multivariate statistical analysis， the potential biomarkers of FF in treating ALI were screened by variable importance in the projection（VIP） value>1， P<0.05 from t-test， and log₂fold change（FC）>1 or log₂FC<-1. Kyoto Encyclopedia of Genes and Genomes（KEGG） database combined with MetaboAnalyst were used for pathway analysis of the screened differential metabolites. The protein expression levels of sphingosine-1-phosphate（S1P）， phosphatidylinositol 3-kinase（PI3K）， protein kinase B1（Akt1）， and phosphorylated Akt1（p-Akt1） were examined by Western bolt. The expression levels of interleukin（IL）-6， IL-1β， and tumor necrosis factor（TNF）-α in BALF were detected by enzyme-linked immunosorbent assay（ELISA）. ResultsCompared with the blank group， rats in the model group showed ALI pathological features such as alveolar lumen dilatation， interstitial hemorrhage and massive inflammatory cell infiltration， and the protein concentration in BALF and W/D of the lung tissues were significantly elevated（P<0.01）. Compared with the model group， the low- and high-dose groups of FF as well as the dexamethasone group exhibited reduced pulmonary bronchial hemorrhage in rats， and the protein concentration in BALF and W/D were significantly decreased（P<0.05）， and the lung injury was significantly alleviated. Analysis of rat serum metabolomics revealed that FF downregulated 38 biomarkers. Pathway enrichment analysis showed that FF primarily exerted therapeutic effects through 7 key metabolic pathways， including arginine biosynthesis， sphingomyelin metabolism， alanine， aspartate and glutamate metabolism， taurine and hypotaurine metabolism， α-linolenic acid metabolism， niacin and nicotinamide metabolism， and retinol metabolism. The results of Western bolt and ELISA showed that， compared with the blank group， the model group exhibited significantly elevated expression levels of S1P， PI3K， Akt1 and p-Akt1 proteins in the lung tissues， as well as increased expression levels of IL-6， IL-1β and TNF-α in BALF（P<0.01）. Compared with the model group， the expression levels of the aforementioned indicators were significantly downregulated in the low- and high-dose FF groups as well as the dexamethasone group（P<0.05， P<0.01）. ConclusionFF may play a role in ALI by regulating amino acid metabolism and lipid metabolism， and its mechanism may be related to the inhibition of S1P/PI3K/Akt1 signaling pathway to attenuate the inflammatory response caused by ALI.

This study aims to explore the pharmacodynamic material basis of Jinbei Oral Liquid(JBOL) against idiopathic pulmonary fibrosis(IPF) based on serum pharmacochemistry and network pharmacology. The ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technology was employed to analyze and identify the components absorbed into rat blood after oral administration of JBOL. Combined with network pharmacology, the study explored the pharmacodynamic material basis and potential mechanism of JBOL against IPF through protein-protein interaction(PPI) network construction, "component-target-pathway" analysis, Gene Ontology(GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. First, a total of 114 compounds were rapidly identified in JBOL extract according to the exact relative molecular mass, fragment ions, and other information of the compounds with the use of reference substances and a self-built compound database. Second, on this basis, 70 prototype components in blood were recognized by comparing blank serum with drug-containing serum samples, including 28 flavonoids, 25 organic acids, 4 saponins, 4 alkaloids, and 9 others. Finally, using these components absorbed into blood as candidates, the study obtained 212 potential targets of JBOL against IPF. The anti-IPF mechanism might involve the action of active ingredients such as glycyrrhetinic acid, cryptotanshinone, salvianolic acid B, and forsythoside A on core targets like AKT1, TNF, and ALB and thereby the regulation of multiple signaling pathways including PI3K/AKT, HIF-1, and TNF. In conclusion, JBOL exerts the anti-IPF effect through multiple components, targets, and pathways. The results would provide a reference for further study on pharmacodynamic material basis and pharmacological mechanism of JBOL.
Drugs, Chinese Herbal/pharmacokinetics* ; Animals ; Tandem Mass Spectrometry ; Network Pharmacology ; Rats ; Chromatography, High Pressure Liquid ; Rats, Sprague-Dawley ; Male ; Idiopathic Pulmonary Fibrosis/metabolism* ; Humans ; Administration, Oral ; Protein Interaction Maps/drug effects* ; Signal Transduction/drug effects*

ObjectiveSerum metabolomics of acute lung injury（ALI） in rats was conducted using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） to explore the similarities and differences in the mechanism of Qingqiao（harvested when the fruits of Forsythiae Fructus were initially ripe and still green in color） and Laoqiao（harvested when the fruits of Forsythiae Fructus were ripe） in the treatment of ALI. MethodA total of 24 SD male rats were acclimatized and fed for 1 week， 6 of them were randomly selected for the blank group and 18 for the experimental group. The ALI model was induced in the experimental group by tracheal intubation with lipopolysaccharide（LPS）. After successfully constructing the ALI model， these rats was randomly divided into model group， Qingqiao group and Laoqiao group， with 6 rats in each group. The Qingqiao and Laoqiao groups were administered orally once a day at a dose of 1.5 g·kg^-1， while the blank and model groups received an equivalent volume of saline for 3 consecutive days. The pathological conditions of rat lung tissues were comprehensively assessed by hematoxylin-eosin（HE） staining， wet-to-dry mass ratio（W/D） of lung tissues， and protein concentration in rat bronchoalveolar lavage fluid（BALF）. The levels of interleukin（IL）-6， IL-1β and tumor necrosis factor（TNF）-α in BALF were quantified using enzyme-linked immunosorbent assay（ELISA）. UPLC-Q-TOF-MS was used to identify and analyze the chemical compositions of Qingqiao and Laoqiao， and serum metabolomics of rats in each group was analyzed， combined with multivariate statistical analysis with variable importance in the projection（VIP） value>1， P<0.05 from t-test， and fold change（FC）≥1.5 or FC≤0.5 to screen the differential metabolites Qingqiao and Laoqiao for the treatment of ALI. The Kyoto Encyclopedia of Genes and Genomes（KEGG） database was used in combination with MetaboAnalyst for the metabolic pathway analysis of the screened differential metabolites. ResultCompared with the blank group， rats in the model group exhibited enlarged alveolar lumen， ruptured alveoli， interstitial hemorrhage， bronchial exudation of a large number of neutrophils and erythrocytes， and a significant increase in the protein concentration in the BALF and the W/D value of the lung tissues（P<0.01）. In contrast， compared with the model group， rats in the Qingqiao group and the Laoqiao group showed reduced bronchial hemorrhage in the lungs， and the protein concentration in the BALF and the W/D value of the lung tissues were significantly decreased（P<0.01）， the lung injury was significantly alleviated， but more obvious in the Qingqiao group. Compared with the blank group， the expression levels of IL-6， IL-1β and TNF-α in the BALF of the model group were significantly higher（P<0.01）. Additionally， compared with the model group， the expression levels of IL-6， IL-1β and TNF-α in the Qingqiao and Laoqiao groups were significantly lower（P<0.01）. The chemical composition analysis of Qingqiao and Laoqiao revealed that 63 components were detected in Qingqiao and 55 components were detected in Laoqiao， with 47 common components， 16 components unique to Qingqiao and 8 components unique to Laoqiao. Characterizing the differences in serum metabolomics in rats， 19 and 12 metabolites were called back by Qingqiao and Laoqiao， respectively. The metabolic pathway enrichment analysis showed that Qingqiao exerted its therapeutic effects by affecting 6 key metabolic pathways， including linoleic acid metabolism， phenylalanine metabolism， phenylalanine， tyrosine and tryptophan biosynthesis， glycerophospholipid metabolism， α-linolenic acid metabolism， and arachidonic acid metabolism， and Laoqiao exerted therapeutic effects by affecting 6 key metabolic pathways， including linoleic acid metabolism， arachidonic acid metabolism， sphingolipid metabolism， phenylalanine metabolism， ascorbate and aldarate metabolism， and glycerophospholipid metabolism. ConclusionQingqiao and Laoqiao have therapeutic effects on ALI， and Qingqiao is more effective. Both of them can play a therapeutic role in ALI by regulating amino acid metabolism and lipid metabolism， but the metabolic pathways affected by them are different.

Rapid epidemiological screening for tuberculosis (TB) usually uses tuberculin pure protein derivative (PPD) skin test, which has limitations such as low specificity and high side effects. ESAT-6 and CFP-10 are secreted proteins of Mycobacterium tuberculosis, but the related genes are missing from Bacillus Calmette-Guerin (BCG). In this study, the fusion protein ESAT6-CFP10 (EC) was expressed and purified, and prepared into chitosan nanoparticles (EC-NPs), which were loaded into the microneedle patch and carried out the preliminary test of tuberculosis skin test. The drug loading capacity of MNP-EC-NPs (microneedle patch, MNP) can reach 0.03 μg per needle and 1.92 μg per patch. The shelf life of MNP-EC-NPs can reach 6 months at room temperature, and it can effectively penetrate the epidermis. Volunteer skin test results showed that MNP-EC-NPs can effectively distinguish between BCG vaccinators, and can effectively show positive reaction in the skin of tuberculosis patients without significant side effects. The experiment was approved by the Ethics Committee of Wuhan Pulmonary Hospital [2022 (2)]. In this study, a TB skin test method was established, using ESAT6-CFP10 fusion protein instead of PPD, and using soluble microneedle dosage form, which improved the specificity of TB skin test diagnosis and provided a new technical scheme for TB epidemic screening.

Objective To obtain the monitoring measurement range of quality indicators of red blood cells,plasma and derivatives and leukocyte-reduced apheresis platelets provided by blood stations in Hebei province,explore the distribution of monitoring values and the change of monitoring level,so as to further strengthen the homogenization construction of quality control laboratories in blood stations in Hebei.Methods In 2023,the sampling data of 12 blood stations in Hebei from 2015 to 2022 were collected,scatter plots were made and the range markers were set,and the"mean±SD"line was taken as the upper limit and lower limit of the measurement range.In 2024,the monitoring values in 2023 were added,and the changes of two measurement ranges were compared to analyze the stability and overall level.Results Comparison of the measurement range from 2015 to 2022 and the measurement range from 2015 to 2023 showed that the standard deviation of the content of deleukocyte suspension of red blood cells-hemoglobin,washed erythrocyte-hemoglobin,washed erythrocyte-su-pernatant protein,cryoprecipitate coagulation factor-FⅧ,fresh frozen plasma-FⅧ,leukocyte-reduced apheresis platelets-leukocyte residue and leukocyte-reduced apheresis platelet-red blood cell concentration decreased from 8.132 to 7.993,6.252 to 6.104,0.273 to 0.267,57.506 to 56.276,0.920 to 0.892,0.653 to 0.644 and 2.653 to 2.603,respectively.The narrowing of the standard deviation range of the above items led to more concentrated monitoring values and reduced disper-sion.Comparison of the measurement range from 2015 to 2022 and the measurement range from 2015 to 2023 showed that the mean value of leukocyte residue of the deleukocyte suspension of red blood cells,hemoglobin content of the wash eryth-rocyte,protein content of supernatant of the wash erythrocyte,hemolysis rate of the wash erythrocyte,FⅧ content of the cryoprecipitate coagulation factor,plasma protein content of the fresh frozen plasma,FⅧ content of the fresh frozen plasma,platelet content of the leukocyte-reduced apheresis platelets changed from 0.362 to 0.476,44.915 to 44.861,0.280 to 0.283,0.137 to 0.142,133.989 to 133.271,60.262 to 60.208,1.301 to 1.277 and 3.036 to 3.033,respectively,and was closer to the national standard line,which reflects an increase in the number of unqualified monitoring values or values close to the national standard line in 2023.The long-term qualified rate of coagulation items was low,and no improvement has been ob-served.The stability of biochemical items has been enhanced but overall deviation has occurred,with the average value close to the national standard line.The possibility of subsequent testing failure has increased.The counting items showed no obvi-ous common characteristics.Conclusion The use of"mean±SD"in the analysis can visually display the distribution of mo-nitoring values of different items in Hebei,forming an indicator measurement range covering the past nine years.It shows the characteristics of each item,and provides reference for subsequent quality control laboratory data analysis of each blood sta-tions to takes active measures to improve the monitoring level.

Background and Objectives: Angiographic assessment of coronary stenosis severity using quantitative coronary angiography (QCA) is often inconsistent with that based on fractional flow reserve (FFR) or intravascular ultrasound (IVUS). We investigated the incidence of discrepancies between QCA and FFR or IVUS, and the outcomes of FFR- and IVUS-guided strategies in discordant coronary lesions. Methods: This study was a post-hoc analysis of the FLAVOUR study. We used a QCA-derived diameter stenosis (DS) of 60% or greater, the highest tertile, to classify coronary lesions as concordant or discordant with FFR or IVUS criteria for percutaneous coronary intervention (PCI). The patient-oriented composite outcome (POCO) was defined as a composite of death, myocardial infarction, or revascularization at 24 months. Results: The discordance rate between QCA and FFR or IVUS was 30.2% (n=551). The QCAFFR discordance rate was numerically lower than the QCA-IVUS discordance rate (28.2% vs. 32.4%, p=0.050). In 200 patients with ≥60% DS, PCI was deferred according to negative FFR (n=141) and negative IVUS (n=59) (15.3% vs. 6.5%, p<0.001). The POCO incidence was comparable between the FFR- and IVUS-guided deferral strategies (5.9% vs. 3.4%, p=0.479).Conversely, 351 patients with DS <60% underwent PCI according to positive FFR (n=118) and positive IVUS (n=233) (12.8% vs. 25.9%, p<0.001). FFR- and IVUS-guided PCI did not differ in the incidence of POCO (9.5% vs. 6.5%, p=0.294). Conclusions The proportion of QCA-FFR or IVUS discordance was approximately one third for intermediate coronary lesions. FFR- or IVUS-guided strategies for these lesions were comparable with respect to POCO at 24 months.