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.

Humans ; Diabetes Mellitus, Type 1 ; Hypoglycemia/chemically induced* ; Hypoglycemic Agents/adverse effects* ; China ; Blood Glucose ; Insulin

Objective:To investigate the causality between intestinal flora and hypertrophic scars (HS) of human.Methods:This study was a study based on two-sample Mendelian randomization (TSMR) analysis. The data on intestinal flora ( n=18 473) and HS ( n=208 248) of human were obtained from the genome-wide association study database. Genetically variable genes at five levels (phylum, class, order, family, and genus) of known intestinal flora, i.e., single nucleotide polymorphisms (SNPs), were extracted as instrumental variables for linkage disequilibrium (LD) analysis. Human genotype-phenotype association analysis was performed using PhenoScanner V2 database to exclude SNPs unrelated to HS in intestinal flora and analyze whether the selected SNPs were weak instrumental variables. The causal relationship between intestinal flora SNPs and HS was analyzed through four methods of TSMR analysis, namely inverse variance weighted (IVW), MR-Egger regression, weighted median, and weighted mode. Scatter plots of significant results from the four aforementioned analysis methods were plotted to analyze the correlation between intestinal flora SNPs and HS. Both IVW test and MR-Egger regression test were used to assess the heterogeneity of intestinal flora SNPs, MR-Egger regression test and MR-PRESSO outlier test were used to assess the horizontal multiplicity of intestinal flora SNPs, and leave-one-out sensitivity analysis was used to determine whether HS was caused by a single SNP in the intestinal flora. Reverse TSMR analyses were performed for HS SNPs and genus Intestinimonas or genus Ruminococcus2, respectively, to detect whether there was reverse causality between them. Results:A total of 196 known intestinal flora, belonging to 9 phyla, 16 classes, 20 orders, 32 families, and 119 genera, were obtained, and multiple SNPs were obtained from each flora as instrumental variables. LD analysis showed that the SNPs of the intestinal flora were consistent with the hypothesis that genetic variation was strongly associated with exposure factors, except for rs1000888, rs12566247, and rs994794. Human genotype-phenotype association analysis showed that none of the selected SNPs after LD analysis was excluded and there were no weak instrumental variables. IVW, MR-Egger regression, weighted median, and weighted mode of TSMR analysis showed that both genus Intestinimonas and genus Ruminococcus2 were causally associated with HS. Among them, forest plots of IVW and MR-Egger regression analyses also showed that 16 SNPs (the same SNPs number of this genus below) of genus Intestinimonas and 15 SNPs (the same SNPs number of this genus below) of genus Ruminococcus2 were protective factors for HS. Further, IVW analysis showed that genus Intestinimonas SNPs (with odds ratio of 0.62, 95% confidence interval of 0.41-0.93, P<0.05) and genus Ruminococcus2 SNPs (with odds ratio of 0.62, 95% confidence interval of 0.40-0.97, P<0.05) were negatively correlated with the risk of HS. Scatter plots showed that SNPs of genus Intestinimonas and genus Ruminococcus2 were protective factors of HS. Both IVW test and MR-Egger regression test showed that SNPs of genus Intestinimonas (with Q values of 5.73 and 5.76, respectively, P>0.05) and genus Ruminococcus2 (with Q values of 13.67 and 15.61, respectively, P>0.05) were not heterogeneous. MR-Egger regression test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity (with intercepts of 0.01 and 0.06, respectively, P>0.05); MR-PRESSO outlier test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity ( P>0.05). Leave-one-out sensitivity analysis showed that no single intestinal flora SNP drove the occurrence of HS. Reverse TSMR analysis showed no reverse causality between HS SNPs and genus Intestinimonas or genus Ruminococcus2 (with odds ratios of 1.01 and 0.99, respectively, 95% confidence intervals of 0.97-1.06 and 0.96-1.04, respectively, P>0.05). Conclusions:There is a causal relationship between intestinal flora and HS of human, in which genus Intestinimonas and genus Ruminococcus2 have a certain effect on inhibiting HS.

Objective To investigate whether the extracts of Patrinia heterophylla(MTH)inhibits the activation of macrophages induced by lipopolysaccharide(LPS)in vitro and the inflammatory response induced in vivo by suppressing the nuclear factor kappa B(NF-κB)signaling pathway.Methods Cellular studies:RAW264.7 cells were divided into 6 groups:control group,LPS group,LPS+Dexamethasone(DEX)group and LPS+MTH(low,medium,high dose)groups.The LPS group,LPS+DEX and LPS+MTH group were induced with a final concentration of 100 ng/ml LPS.While the LPS+DEX group was additionally treated with 5.0 ng/ml DEX,the LPS+MTH group was additionally treated with MTH(final concentrations of 0.1,0.2 and 0.4 mg/ml).The cell activity was detected using CCK-8 assay,cell invasion was detected using Transwell assay,cell apoptosis was detected using flow cytometry,and interleukin-6(IL-6),interleukin-17(IL-17)and tumor necrosis factor-α(TNF-α)were detected using real-time fluorescence quantitative PCR and enzyme-linked immunosorbent assay,respectively.The expression and secretion levels of nitric oxide(NO)in cells were detected by Griess assay,total reactive oxygen species(ROS)levels were detected by flow cytometry.The phosphorylation level of p65 and inhibitor of κB(IκB)were detected by protein immunoblotting assay.The transcriptional activity was detection by luciferase reporter gene assay.Animal studies:50 rats were randomly divided into 5 groups,10 per group,namely the control group,LPS group,LPS+DEX group,LPS+MTH low-dose group(6 g/kg)and LPS+MTH high-dose group(24 g/kg).LPS was injected into the lungs of rats,and the groups were orally administered at 36 h,24 h,12 h before modeling,and 12 h,24 h after modeling.12 h after the last administration,bronchoalveolar lavage fluid was collected,and the IL-6,IL-17,TNF-α and NF-κB signaling pathway-related indicators in the bronchoalveolar lavage fluid were measured.Results Cellular studies:Compared with the control group,the cell activity,invasion,apoptosis,IL-6,IL-17 and TNF-α mRNA and protein,NO,ROS,phosphorylation level of P536 protein S536 site and IκB protein S32 site and transcription activity of NF-κB had significantly increased in the LPS group(all P＜0.05).Compared with the LPS group,the cell activity,invasion,IL-6,IL-17,and TNF-αmRNA and protein,NO,ROS,phosphorylation level of P536 protein S536 site and IκB protein S32 site and transcription activity of NF-κB had significantly decreased in 3 LPS+MTH groups(all P＜0.05),and apoptosis was significantly increased in 3 LPS+MTH groups(all P＜0.05).All of which showed a dose-dependent trend of MTH.Animal studies:Compared with the control group,the LPS group showed a significant increase in IL-6,IL-17,TNF-α and phosphorylation levels of p65 protein at S536 site and IκB protein at S32 site(all P＜0.05).Compared with the LPS group,the 2 LPS+MTH groups showed a significant decrease in IL-6,IL-17,TNF-α and phosphorylation levels of p65 protein at S536 site and IκB protein at S32 site(all P＜0.05).These indicators showed a dose-dependent trend with MTH.Conclusion MTH can inhibit the activation of mouse macrophage RAW264.7 induced by LPS and the inflammatory response in the lungs of rats induced by LPS,which may be related to the inhibition of the NF-κB signaling pathway.

Objective To investigate the factors affecting the prognosis of endovascular treatment(EVT)for acute vertebrobasilar artery occlusion(AVBAO)within 24 h of onset of disease.Methods General and clinical data of AVBAO patients admitted to the Department of Cerebrovascular Diseases,Henan Provincial People's Hospital who received EVT within 24h of onset from October 2020 to September 2023 were retrospectively and consecutively included,including age,sex,stroke-related risk factors(hyperlipidemia,hypertension,diabetes mellitus,atrial fibrillation,coronary artery disease,smoking,and previous stroke),preoperative National Institutes of Health stroke scale(NIHSS)score,preoperative modified Rankin scale(mRS)score,form of onset,preoperative intravenous thrombolysis,posterior circulation Alberta stroke program early CT score(pc-ASPECTS),basilar artery on computed tomography angiography(BATMAN)score,site of occlusion(intracranial segment of vertebral artery,basilar artery),and surgical procedure(direct aspiration and/or stent-retrieval,balloon dilatation,stenting,etc.First-line stenting or balloon dilatation is direct angioplasty;if blood flow cannot be maintained after thrombectomy,further balloon dilatation and/or stenting is required as remedial angioplasty),onset-to-puncture time,puncture-to-recanalization time,and postprocedure immediate modified thrombolysis in cerebral infarction(mTICI)grading(successful recanalization was defined as mTICI grading 2b or 3),and perioperative complications(intraprocedural thrombus migration,intraprocedural reocclusion,intraprocedural dissection,postoperative hemorrhagic transformation within 3 d,and symptomatic intracranial hemorrhage[sICH]).Patient prognosis was assessed by mRS score at 90 d postoperatively.The mRS score≤3 was classified as good prognosis,and mRS score＞3 was classified as poor prognosis.Indicators with P＜0.1 in the results of univariate analysis were included,and variables were screened by backward elimination and subjected to multifactorial Logistic regression analysis to analyze the factors influencing the prognosis of AVBAO patients undergoing EVT within 24 h of the onset of the disease.Results A total of 149 AVBAO patients who underwent EVT were included,including 79 patients with good prognosis,70 patients with poor prognosis,145 patients with successful revascularization,34 patients with perioperative complications,and 32 patients with death.(1)The results of univariate analysis showed that compared with patients with poor prognosis,patients with good prognosis had lower preoperative NIHSS scores(16.0[12.0,23.0]vs.24.5[16.8,31.3],Z=-4.280,P＜0.01)and preoperative mRS scores(4[4,4]vs.5[4,5],Z=-4.711,P＜0.01),a lower percentage of diabetes mellitus(15.2％[12/79]vs.35.7％[25/70],x2=8.376,P=0.004),and the incidence of postoperative hemorrhagic transformation within 3d(7.6％[6/79]vs.25.7％[18/70],x2=-0.246,P=0.003)and the incidence of sICH(1.3％[1/79]vs.14.3％[10/70],x2=-0.249,P=0.002)were significantly lower in patients with good prognosis than that in patients with poor prognosis.(2)Age,hyperlipidemia,diabetes mellitus,preoperative NIHSS score,preoperative mRS score,postoperative hemorrhagic transformation within 3 d and sICH were included in multifactorial Logistic regression analysis,which showed that hyperlipidemia(OR,2.433,95％CI 1.088-5.441),diabetes mellitus(OR,2.797,95％CI 1.168-6.701),high preoperative NIHSS score(OR,3.715,95％CI 1.684-8.195),and postoperative sICH within 3 d(OR,19.681,95％CI 1.984-195.192)were the independent risk factors for poor prognosis of patients with AVBAO who underwent EVT within 24 h of onset(all P＜0.05).Conclusion Hyperlipidemia,diabetes mellitus,high preoperative NIHSS score,and postoperative sICH within 3 d were independent risk factors for poor prognosis in AVBAO patients who underwent EVT within 24 h of onset.

Objective:To explore the differences in bacterial community structure between proximal colon cancer (PC), distal colon cancer (DC), and rectal cancer (RC), and the values of featured microbiota in differentiating PC with tumor markers.Methods:This case-control study enrolled 85 newly diagnosed colorectal cancer patients, including 22 PC, 15 DC and 48 RC patients, and 8 colorectal adenoma patients from May 2019 to July 2022 at the Department of General Surgery, Anyang Oncology Hospital. The blood and fecal samples were collected before surgery and then subjected to biochemical tests for tumor markers and 16S rDNA tests, respectively. SPSS (27.0.1) was applied to perform the t-test, one-way ANOVA, Mann-Whitney U test, Kruskal-Wallis H test, and Chi-Squared Test. Also, the receiver operating characteristic curve (ROC) was plotted on tumor markers and/or f_Bacteroidaceae with SPSS software .Results:All groups had significant differences in the CA125 ( F=3.543, P<0.05), CA72-4 ( F=3.596, P<0.05), and serum tumor-associated materials (TAM) levels ( F=5.787, P<0.01). In PC group, the levels of CA125 [PC vs RC, (36.84±6.30) kU/L vs (12.73±4.21) kU/L, P<0.01] and CA72-4 [PC vs RC, (45.56±10.86) kU/L vs (3.30±7.63) kU/L, P<0.01] were significantly higher than that of the RC group, while the level of TAM was remarkably elevated in PC group than in RC group [PC vs RC, (124.84±5.19) U/ml vs (102.44±3.63) U/ml, P<0.001] and CRA group [PC vs CRA, (124.84±5.19) U/ml vs (95.39±8.42) U/ml, P<0.01]. The LEfSe analysis showed that the featured microbiota in the PC group included f_Bacteroidaceae, f_Neisseriaceae, f_Clostridiaceae_1, f_Spirochaetaceae, and so on. The largest area under the ROC belonged to the combination of TAM and f_Bacteroidaceae, which reached 0.845 (95% CI 0.747-0.944), with sensitivity being 0.857 and specificity being 0.815. Conclusions:There is heterogeneity in gut microbiota composition among PC, DC, RC, and CRA. The combination of gut microbiota and tumor biomarkers demonstrated good differentiating effects in proximal colon cancers.

OBJECTIVE To observe the effects of Panax quinquefolium-Acorus calamus on learning and memory abilities in diabetes mellitus(DM) mice and investigate the mechanism of Panax quinquefolium-Acorus calamus in treating diabetic cognitive impairment(DCI) through network pharmacology and animal experiments. METHODS Diabetic mouse model was established by intraperitoneal injection of streptozotocin(80 mg·kg−1), followed by 8 weeks of oral administration and assessment of drug efficacy using the Morris water maze. The active ingredients and targets of Panax quinquefolium-Acorus calamus were collected using TCMSP, Swiss Target Prediction, and Gene Cards. The protein-protein interaction network of "Traditional Chinese Medicine-Ingredient-Disease targets" was constructed using the String platform and Cytoscape, visualized, and subjected to enrichment analysis using the Metascape database. The anti-DCI mechanism of Panax quinquefolium-Acorus calamus was examined through ELISA and Western blotting, while changes in hippocampal neurons of diabetic mice were observed using HE staining. RESULTS Panax quinquefolium-Acorus calamus reduced the escape latency of diabetic mice(P<0.05), without significant impact on swimming speed. Network pharmacology results indicated that the main components of Panax quinquefolium-Acorus calamus in treating DCI were ginsenoside Re, ginsenoside Rh2, and shanjin phenol, which regulated the Nrf2-Keap1 signaling pathway to treat DCI. Animal experiments demonstrated that Panax quinquefolium-Acorus calamus increased SOD activity(P<0.05), decreased MDA levels(P<0.01), enhanced the expression of HO-1, Keap1, Nrf2 in mouse brain(P<0.01), and alleviated the loosening of granule cell arrangement and nuclear condensation in the hippocampal CA1, CA3, and DG regions. CONCLUSION Using animal experiments combined with network pharmacology, this study preliminarily elucidates the potential targets and mechanisms of Panax quinquefolium-Acorus calamus in intervening DCI, and predictes the molecular basis for its intervention in DCI through molecular docking, providing insights for further in-depth research on Panax quinquefolium-Acorus calamus.