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.

AIM: To compare the clinical outcomes of extended depth-of-focus intraocular lenses(EDOF IOLs)using either micromonovision implantation or mixed implantation of EDOF and diffractive bifocal IOLs.METHODS: This retrospective clinical trial included 130 patients(260 eyes), who were divided into two groups. Group RR comprised 70 patients(140 eyes)bilaterally implanted with ZXR00 IOLs(Tecnis ZXR00, where one target was -0.5 D to -0.75 D and the other was 0 to -0.25 D). Group RM comprised 60 patients(120 eyes)unilaterally implanted with both ZXR00 and ZMB00 IOLs(Tecnis ZMB00, 0 to -0.25 D). Postoperative outcomes were compared after 3 mo, including visual acuity, defocus curves, stereoacuity, modulation transfer functions(MTFs), higher-order aberrations, and Visual Function-14(VF-14)questionnaire responses.RESULTS: Group RR had superior bilateral intermediate vision, while the group RM had superior bilateral near vision(both P<0.05). Group RM also exhibited superior MTFs and reduced higher-order aberrations(both P<0.05). Stereoacuity and VF-14 questionnaire results showed no statistically significant difference between groups(P>0.05).CONCLUSION: The implantation of micromonovision has significantly improved near vision. IOLs and their collocation can be customized according to individual patient needs to achieve precise treatment and provide cataract patients with high-quality vision.

AIM: To compare the clinical outcomes of extended depth-of-focus intraocular lenses(EDOF IOLs)using either micromonovision implantation or mixed implantation of EDOF and diffractive bifocal IOLs.METHODS: This retrospective clinical trial included 130 patients(260 eyes), who were divided into two groups. Group RR comprised 70 patients(140 eyes)bilaterally implanted with ZXR00 IOLs(Tecnis ZXR00, where one target was -0.5 D to -0.75 D and the other was 0 to -0.25 D). Group RM comprised 60 patients(120 eyes)unilaterally implanted with both ZXR00 and ZMB00 IOLs(Tecnis ZMB00, 0 to -0.25 D). Postoperative outcomes were compared after 3 mo, including visual acuity, defocus curves, stereoacuity, modulation transfer functions(MTFs), higher-order aberrations, and Visual Function-14(VF-14)questionnaire responses.RESULTS: Group RR had superior bilateral intermediate vision, while the group RM had superior bilateral near vision(both P<0.05). Group RM also exhibited superior MTFs and reduced higher-order aberrations(both P<0.05). Stereoacuity and VF-14 questionnaire results showed no statistically significant difference between groups(P>0.05).CONCLUSION: The implantation of micromonovision has significantly improved near vision. IOLs and their collocation can be customized according to individual patient needs to achieve precise treatment and provide cataract patients with high-quality vision.

Probiotics play a crucial role in colon cancer treatment by metabolizing prebiotics to generate short-chain fatty acids (SCFAs). Colon cancer patients are frequently propositioned to supplement with probiotics to enhance the conversion and utilization of prebiotics. Nevertheless, the delivery and colonization of probiotics is hindered by the harsh conditions of gastrointestinal tract (GIT). Here, we devised a straightforward yet potent modified prebiotic-based "shield" (Gelatin-Inulin, GI), employing dietary inulin and natural polymer gelatin crosslinked via hydrogen bonding for enveloping Lactobacillus reuteri (Lr) to formulate synbiotic hydrogel capsules (Lr@Gl). The GI "shield" serves as a dynamic barrier, augmenting the resistance of Lr to gastric acid and facilitating its bioactivity and adherence in the GIT, synergizing with Lr to elicit an anti-tumor effect. Simultaneously, Lr@GI demonstrates anti-tumor effects by depleting glutathione to release reactive oxygen species, accompanied by the activation of NLRP3 (NOD-like receptor family pyrin domain containing 3), and the induction M1 macrophage polarization. Furthermore, Lr@GI can not only promote the recovery of intestinal barrier but also regulate intestinal flora, promoting the production of SCFAs and further exerting anti-tumor effect. Crucially, Lr@GI also potentiates the anti-tumor effect of 5-Fluorouracil. The construction and synergistic anti-tumor mechanism of synbiotic hydrogel capsules system provide valuable insights for gut microbial tumor therapy.

The ability of cells to sense and adapt to metabolic changes and environmental variations is essential for their functions. Recent advances in synthetic biology have uncovered increasing mechanisms through which cells detect changes in metabolism and environmental conditions, leading to broader applications. However, a systematic review on the regulation of cellular metabolism and environmental adaption is currently lacking. This article presents a comprehensive overview of this field from three perspectives. First, it introduces key transmembrane and sensor proteins involved in the cellular perception of metabolic and environmental changes. Next, it summarizes the adaptive regulation mechanisms that natural cells employ when confronted with intracellular and extracellular metabolic changes. Finally, the review explores the application scenarios based on cellular adaptive regulation in three aspects: dynamic control, rational metabolic engineering, and adaptive evolution and makes an outlook on the future development directions in this field. This review not only provides a comprehensive perspective on the mechanisms by which cells sense metabolic and environmental variations, but also lays a theoretical foundation for further innovations in the field of synthetic biology. With the continuous advancement of future technologies, a deeper understanding of cellular adaptive regulation mechanisms holds great potential to drive the development and application of novel biomanufacturing platforms.
Adaptation, Physiological ; Synthetic Biology ; Metabolic Engineering/methods* ; Environment ; Bacteria/genetics*

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.

Objective:To investigate the impact of high-density lipoprotein (HDL) subfraction cholesterol, measured by the vertical auto profile (VAP) technique based on vertical density gradient ultracentrifugation, on the occurrence and progression of coronary heart disease.Methods:This retrospective case-control study consecutively enrolled 94 inpatients diagnosed with coronary artery disease (CAD) by percutaneous coronary angiography at Ningbo University Affiliated First Hospital between June 2023 and June 2024 (CAD group), and 48 outpatients from the cardiology department without carotid or coronary atherosclerosis(non-CAD group). The VAP technique was employed to measure HDL subfraction cholesterol levels (HDL 3-C and HDL 2-C) and their subtypes (HDL 2a-C, HDL 2b-C, HDL 2c-C; HDL 3a-C, HDL 3b-C, HDL 3c-C, HDL 3d-C). Logistic regression analysis was performed to assess the association between HDL subfraction composition and CAD. CAD patients were further stratified by the number of affected coronary vessels (left anterior descending artery, left circumflex artery, and right coronary artery): 44 with single-vessel disease, 22 with double-vessel disease, and 28 with triple-vessel disease for correlation analysis. All CAD patients underwent 6-month clinical and telephone follow-up to record major adverse cardiovascular events (MACE), including acute myocardial infarction, stroke, and repeat revascularization. Using the median HDL 3d-C level (0.064 mmol/L) as cutoff, CAD patients were divided into high-level ( n=48) and low-level ( n=46) subgroups for Kaplan-Meier survival analysis with log-rank testing. Results:Compared with non-CAD controls, CAD patients showed significantly higher HDL 3d-C [0.064 (0.041, 0.095) mmol/L vs 0.055 (0.038, 0.067) mmol/L] and HDL 3b-C [0.031 (0.001, 0.054) mmol/L vs 0.007 (0.004, 0.029) mmol/L], lower HDL 3c-C (0.220±0.080 mmol/L vs 0.254±0.062 mmol/L) and HDL 3a-C [0.282 (0.224, 0.351) mmol/L vs 0.334 (0.269, 0.433) mmol/L] (all P<0.05). Logistic regression revealed that HDL2b-C was a protective factor against atherosclerosis severity ( OR=0.914, 95% CI 0.896-0.987, P<0.001); HDL 3d-C served as both a CAD risk factor ( OR=2.303,95% CI 1.740-3.047, P<0.001) and disease progression indicator ( OR=1.224, 95% CI 1.123-1.335, P=0.025). MACE patients ( n=6) had elevated HDL3d-C versus non-MACE cases ( n=88) [0.120 (0.083, 0.173) mmol/L vs 0.061 (0.037, 0.092) mmol/L, P<0.05]. The high HDL 3d-C subgroup demonstrated significantly lower 6-month survival (χ2=4.777, P=0.029). Conclusion:Contrary to conventional understanding, our study reveals that HDL2b serves as a protective factor against coronary artery disease progression, whereas HDL 3d-C acts not only as a pathogenic factor for CAD but also as a critical determinant of CAD-related adverse events.

Objective:To analyze the blood-transition prototype components and metabolites of Fengliaoxing Fengshi Dieda medicinal liquor.Methods:Ultra-high performance liquid chromatographyquadrupole/electrostatic field orbital trap high resolution mass spectrometry (UHPLC-Q Exactive Focus MS/MS) technique was used to compare the chromatogram differences of Fengliaoxing Fengshi Dieda medicinal liquor extract, blank serum and drug-containing serum. According to the retention time, relative molecular weight and the ratio with primary and secondary ion fragments provided by MS, the prototype components and metabolites of Fengliaoxing Fengshi Dieda medicinal liquor extract were analyzed in serum of rats after oral administration. The detection conditions were as follows: the mobile phase of methanol (A)-0.1% formic acid solution (B) for elution gradient (0-5 min, 5%A; 5-60 min, 5%-95%A; 60-65 min, 95%A), the flow rate of 0.3 ml/min, heated electrospray ionization, detection range of m/z 80-1 200, positive and negative ion scanning modes.Results:A total of 31 transitional components were detected in the serum, of which 9 were prototype components and 22 were metabolites. The 9 prototype components were identified as phenylacetaldehyde, baogongteng C/ erycibellin, p-coumaric acid, 5-Hydroxymethylfurfural, quinic acid, paeonol, 3-Hydroxybenzaldehyde, salicylic acid, and isourecumenol. The 22 metabolites mainly consist of 11 organic acid components, 3 indole components, 2 organic phenolic components, 2 alkaloid components, 1 nucleoside component, 1 amino acid component, 1 lactone component, and 1 sulfonic component. The metabolic pathways were mainly glucuronidation, sulfation and others, which by phase Ⅱ metabolism.Conclusion:Organic phenols and organic acids are the main components that enter the body of Fengliaoxing Fengshi Dieda Medicinal Liquor, while alkaloid compounds and organic acid components may be potential active ingredients for its pharmacological effects.

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.