BACKGROUND: The FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial demonstrated that percutaneous coronary intervention (PCI) lesion selection using quantitative flow ratio (QFR) measurement, a novel angiography-based approach for estimating fractional flow reserve, improved two-year clinical outcomes compared with standard angiography guidance. This study aimed to assess the cost-effectiveness of QFR-guided PCI from the perspective of the current Chinese healthcare system. METHODS: This study is a pre-specified analysis of the FAVOR III China trial, which included 3825 patients randomized between December 25, 2018, and January 19, 2020, from 26 centers in China. Patients with stable or unstable angina pectoris or those ≥72 hours post-myocardial infarction who had at least one lesion with a diameter stenosis between 50% and 90% in a coronary artery with a ≥2.5 mm reference vessel diameter by visual assessment were randomized to a QFR-guided strategy or an angiography-guided strategy with 1:1 ratio. During the two-year follow-up, data were collected on clinical outcomes, quality-adjusted life-years (QALYs), estimated costs of index procedure hospitalization, outpatient cardiovascular medication use, and rehospitalization due to major adverse cardiac and cerebrovascular events (MACCE). The primary analysis calculated the incremental cost-effectiveness ratio (ICER) as the cost per MACCE avoided. An ICER of ¥10,000/MACCE event avoided was considered economically attractive in China. RESULTS: At two years, the QFR-guided group demonstrated a reduced rate of MACCE compared to the angiography-guided group (10.8% vs . 14.7%, P <0.01). Total two-year costs were similar between the groups (¥50,803 ± 21,121 vs . ¥50,685 ± 23,495, P = 0.87). The ICER for the QFR-guided strategy was ¥3055 per MACCE avoided, and the probability of QFR being economically attractive was 64% at a willingness-to-pay threshold of ¥10,000/MACCE avoided. Sensitivity analysis showed that QFR-guided PCI would become cost-saving if the cost of QFR were below ¥3682 (current cost: ¥3800). Cost-utility analysis yielded an ICER of ¥56,163 per QALY gained, with a 53% probability of being cost-effective at a willingness-to-pay threshold of ¥85,000 per QALY gained. CONCLUSION: In patients undergoing PCI, a QFR-guided strategy appears economically attractive compared to angiographic guidance from the perspective of the Chinese healthcare system. TRIAL REGISTRATION ClinicalTrials.gov , NCT03656848.
Humans ; Cost-Benefit Analysis ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Angiography/methods* ; Middle Aged ; Aged ; Coronary Artery Disease/surgery* ; Quality-Adjusted Life Years ; Fractional Flow Reserve, Myocardial/physiology*

Objective:To evaluate the long-term outcomes and predictors of coronary atherosclerotic lesions deemed functionally non-ischemic (quantitative flow ratio(QFR)>0.80) and deferred from intervention.Methods:This study is a post-hoc analysis of the FAVOR Ⅲ China trial, which enrolled 3 825 patients with stable or unstable angina pectoris or with myocardial infarction occurring at least 72 hours prior to screening, between December 5, 2018 and January 9, 2020 from 26 research centers in China. Coronary vessels with QFR>0.80 and without interventional treatment were analyzed in this study. The primary endpoint was 3-year target vessel revascularization. Vessels with revascularization (revascularized group) during follow-up were matched 1∶1 using propensity score matching to comparable vessels without revascularization (non-revascularized group). Multivariate Cox regression analysis was used to identify the risk factors for target vessel revascularization (TVR).Results:A total of 6 212 functionally negative vessels with deferred intervention were included in the final analysis, among which 153 vessels (2.5%) underwent TVR during a 3-year follow-up. Prior to propensity score matching, 6 059 vessels comprised the non-revascularized group. At the vessel level, compared to the non-revascularized group, the revascularized group exhibited a significantly higher proportion of males (79.1% (121/153) vs. 70.2% (4 253/6 059), P=0.018), higher body mass index ((25.6±4.0) kg/m2 vs. (24.3±5.2) kg/m2, P=0.003), and a higher prevalence of hypertension (73.9% (113/153) vs. 65.1% (3 944/6 059), P=0.025). And 152 pairs of vessels were successfully matched. Multivariate Cox regression analysis identified in-stent restenosis lesions ( HR=2.59, 95% CI 1.28-5.23, P=0.008) as an independent risk factor for target vessel revascularization. Conclusions:Coronary lesions classified as functionally non-ischemic at baseline are not entirely stable and may progress to lesions that requiring revascularization over time. In-stent restenosis emerges as a critical independent predictor of revascularization.

Objective:This study aimed to evaluate the therapeutic efficacy of early bedside plasma adsorption (PA) combined with pulse high-volume hemofiltration (PHVHF) in patients with septic shock and acute kidney injury (AKI).Methods:A prospective randomized controlled trial was conducted, enrolling septic shock patients with AKI admitted to the intensive care unit of Linyi Central Hospital between January 2022 and January 2024. Participants were randomly assigned to either the Continuous Veno-Venous Hemofiltration (CVVH) group or the integrated treatment group (PHVHF+PA). Both groups received standard care following the 2021 Surviving Sepsis Campaign guidelines. Both groups received standard treatment according to the 2021 Surviving Sepsis Campaign guidelines. The CVVH group received standard CVVH, while the integrated therapy group underwent PHVHF [substitution fluid rate: 85 mL/(kg·h)] combined with PA. Organ function indices, hemodynamic parameters, inflammatory markers, critical illness scores before treatment, at 24 h and 72 h after treatment, and 28-day survival outcomes were monitored. Categorical data were analyzed using the χ2 test, continuous variables were compared with independent samples t-test, repeated-measures data were analyzed by ANOVA, and 28-day survival was evaluated using Kaplan-Meier curves.Results:A total of 56 septic shock patients with AKI were enrolled and randomly divided into CVVH group ( n=27) and integrated therapy group ( n=29). The baseline characteristics including age, gender, and body mass index were comparable between groups (all P>0.05). No significant differences in organ function or hemodynamic parameters were observed before treatment (all P>0.05). At 24 h post-treatment, both groups showed significant improvements in serum creatinine (Scr), mean arterial pressure, heart rate, and lactate levels (all P<0.05), with reduced norepinephrine requirements ( P<0.05). The integrated treatment group demonstrated significant improvements in oxygenation index (PaO 2/FiO 2), total bilirubin, APACHEⅡ and SOFA scores (all P<0.05). By 72 h, the integrated therapy group exhibited significantly higher PaO 2/FiO 2, platelet counts, and MAP, alongside lower total bilirubin, Scr, HR, norepinephrine dosage, and Lac (all P<0.05). Both groups showed reductions in APACHEⅡ, SOFA scores, procalcitonin, C-reactive protein, TNF-α, IL-6, and IL-10 (all P<0.05). The integrated treatment group had shorter ICU stays [(8.9±2.8) d vs. (11.2±3.6) d, P=0.005), and higher 28-day renal function recovery rates [15(51.7%) vs. 8(29.6%), P=0.033] than CVVH group, though no significant differences were observed in 7-day or 28-day survival rates between groups (both P>0.05). Conclusions:Compared to CVVH, the combined therapy of PHVHF and PA demonstrates superior efficacy in eliminating inflammatory mediators and enhancing organ function. However, this combination does not significantly influence 28-day survival outcomes in patients.

Objective To investigate the effect of endothelial cells in the perivascular niche on the stem cell-like characteristics of osteosarcoma cells and primarily explore the possible molecular mechanism.Methods A co-culture model was established in vitro using SV40T-human umbilical vein endothelial cells(HUVEC-T1)and osteosarcoma stem cells(OSCs)derived from the human osteosarcoma cell line 143B.Thus,there were 2 groups of cells,OSCs and co-cultured OSCs.The self-renewal capacity of OSCs between the 2 groups was assessed using a limiting dilution forming sphere assay.Flow cytometry and Western blotting were used to detect the expression of stem cell marker CD133 and stemness transcription factors SOX2 and NANOG.Fourteen female nude mice(4～6 weeks old,weighing 18～20 g)were randomly and equally divided into 2 groups of subcutaneous xenograft models:the control group(OSCs suspension)and the experimental group(OSCs+HUVEC-T1 mixed suspension).The tumor volume and mass were compared between the 2 xenograft groups.Immunofluorescence(IF)staining was used to verify the spatial proximity between endothelial cells and OSCs in vivo,while immunohistochemistry was employed to compare microvessel density(MVD)and CD133 expression level between the 2 groups.RNA-seq was performed to identify potential signaling pathways of endothelial cells affecting the stemness of OSCs.PCR and Western blotting were applied to confirm the RNA-seq findings.Exogenous protein treatment,IF staining,Western blotting and sphere formation assay were utilized to preliminarily validate the role of the identified pathway in regulating the stemness phenotype of OSCs.Results The in vitro co-culture model of HUVEC-T1 and OSCs was successfully established.Compared with the control group,the co-culture group exhibited significantly enhanced self-renewal ability of OSCs,laeger proportion of the stemness marker CD133+[(8.20±1.64)％vs(4.32±1.34)％,P<0.05],enhanced expression of CD117,SOX2 and NANOG(P<0.05),along with more sphere formation(P<0.05)and elevated SOX2/NANOG protein levels.The xenograft mice from the experimental group showed larger tumor volume(643.10±413.50 vs 247.90±93.66 mm3,P<0.05)and heavier tumor weight(0.52±0.27 vs 0.24±0.10 g,P<0.05)when compared the control group,correspondingly showing increased MVD(22.57±11.84 vs 11.43±5.38,P<0.05)and elevated CD133 expression(P<0.05).IF staining confirmed the adjacency of CD31-labeled endothelial cells and CD133-labeled OSCs in vivo.RNA-seq and functional experiments demonstrated that CXCR4 was highly expressed in co-cultured OSCs,CXCL12 was highly expressed in co-cultured endothelial cells,and exogenous CXCL12 promoted the sphere formation and expression levels of SOX2 and NANOG of OSCs(P<0.05).Conclusion Endothelial cells within the perivascular niche may promote the stemness phenotype of osteosarcoma cells via the CXCL12/CXCR4 pathway.

Objectives:To explore the predictive value of residual Murray's law-based quantitative flow ratio(μQFR)on long-term vessel-oriented composite endpoints(VoCE).Methods:This retrospective study included 3 510 patients from the FAVOR Ⅲ China trial.Offline residual μQFR analysis was performed on all vessels(diameter≥2.5 mm)with 50%-90%stenotic lesions.Patients were stratified into high-,intermediate-,and low-risk groups based on residual μQFR tertiles.The primary endpoint was 3-year VoCE,defined as a composite of cardiac death related to the target vessel,target vessel-related spontaneous myocardial infarction,and ischemia-driven target vessel revascularization.Results:Offline analysis was performed on 5 256 vessels from 3 510 patients.The mean residual μQFR was 0.92±0.75.The high-risk group(residual μQFR≤0.91)with 1 554 patients(1 958 vessels);the intermediate-risk group(residual μQFR 0.92-0.96)with 1 211 patients(1 906 vessels);and the low-risk group(residual μQFR>0.96)with 745 patients(1 392 vessels).Over 3-year follow-up,VoCE occurred in 227 vessels(4.3%).The 3-year VoCE incidence was significantly higher in the high-risk group compared to the intermediate-and low-risk groups(6.2%vs.4.1%vs.2.5%,log-rank P<0.001),primarily driven by ischemia-driven target vessel revascularization(5.0%vs.3.0%vs.1.6%,log-rank P<0.001).Hypertension(OR=0.83,95%CI:0.72-0.96),hypercholesterolemia(OR=0.84,95%CI:0.73-0.97),bifurcation lesions(OR=0.72,95%CI:0.63-0.83),moderate/severe calcification(OR=0.70,95%CI:0.57-0.84),and tandem lesions(OR=0.59,95%CI:0.47-0.75)were independent predictors of lower residual μQFR values.Conclusions:Lower residual μQFR is significantly associated with increased VoCE risk during the 3-year follow up period.

Objectives:To explore the predictive value of residual Murray's law-based quantitative flow ratio(μQFR)on long-term vessel-oriented composite endpoints(VoCE).Methods:This retrospective study included 3 510 patients from the FAVOR Ⅲ China trial.Offline residual μQFR analysis was performed on all vessels(diameter≥2.5 mm)with 50%-90%stenotic lesions.Patients were stratified into high-,intermediate-,and low-risk groups based on residual μQFR tertiles.The primary endpoint was 3-year VoCE,defined as a composite of cardiac death related to the target vessel,target vessel-related spontaneous myocardial infarction,and ischemia-driven target vessel revascularization.Results:Offline analysis was performed on 5 256 vessels from 3 510 patients.The mean residual μQFR was 0.92±0.75.The high-risk group(residual μQFR≤0.91)with 1 554 patients(1 958 vessels);the intermediate-risk group(residual μQFR 0.92-0.96)with 1 211 patients(1 906 vessels);and the low-risk group(residual μQFR>0.96)with 745 patients(1 392 vessels).Over 3-year follow-up,VoCE occurred in 227 vessels(4.3%).The 3-year VoCE incidence was significantly higher in the high-risk group compared to the intermediate-and low-risk groups(6.2%vs.4.1%vs.2.5%,log-rank P<0.001),primarily driven by ischemia-driven target vessel revascularization(5.0%vs.3.0%vs.1.6%,log-rank P<0.001).Hypertension(OR=0.83,95%CI:0.72-0.96),hypercholesterolemia(OR=0.84,95%CI:0.73-0.97),bifurcation lesions(OR=0.72,95%CI:0.63-0.83),moderate/severe calcification(OR=0.70,95%CI:0.57-0.84),and tandem lesions(OR=0.59,95%CI:0.47-0.75)were independent predictors of lower residual μQFR values.Conclusions:Lower residual μQFR is significantly associated with increased VoCE risk during the 3-year follow up period.

Objective:To evaluate the long-term outcomes and predictors of coronary atherosclerotic lesions deemed functionally non-ischemic (quantitative flow ratio(QFR)>0.80) and deferred from intervention.Methods:This study is a post-hoc analysis of the FAVOR Ⅲ China trial, which enrolled 3 825 patients with stable or unstable angina pectoris or with myocardial infarction occurring at least 72 hours prior to screening, between December 5, 2018 and January 9, 2020 from 26 research centers in China. Coronary vessels with QFR>0.80 and without interventional treatment were analyzed in this study. The primary endpoint was 3-year target vessel revascularization. Vessels with revascularization (revascularized group) during follow-up were matched 1∶1 using propensity score matching to comparable vessels without revascularization (non-revascularized group). Multivariate Cox regression analysis was used to identify the risk factors for target vessel revascularization (TVR).Results:A total of 6 212 functionally negative vessels with deferred intervention were included in the final analysis, among which 153 vessels (2.5%) underwent TVR during a 3-year follow-up. Prior to propensity score matching, 6 059 vessels comprised the non-revascularized group. At the vessel level, compared to the non-revascularized group, the revascularized group exhibited a significantly higher proportion of males (79.1% (121/153) vs. 70.2% (4 253/6 059), P=0.018), higher body mass index ((25.6±4.0) kg/m2 vs. (24.3±5.2) kg/m2, P=0.003), and a higher prevalence of hypertension (73.9% (113/153) vs. 65.1% (3 944/6 059), P=0.025). And 152 pairs of vessels were successfully matched. Multivariate Cox regression analysis identified in-stent restenosis lesions ( HR=2.59, 95% CI 1.28-5.23, P=0.008) as an independent risk factor for target vessel revascularization. Conclusions:Coronary lesions classified as functionally non-ischemic at baseline are not entirely stable and may progress to lesions that requiring revascularization over time. In-stent restenosis emerges as a critical independent predictor of revascularization.

This study aimed to preliminarily evaluate the efficacy of posterior debridement and corpectomy via the spinal canal’s lateral wall approach (PDC-SCLWA) for spinal infection after vertebral augmentation (SIAVA). The procedure is characterized as “lateral wall resection for access, anterior lesion removal for debridement, and posterior wall preservation for bone graft fusion.” This distinguishes it from conventional 360° decompression that involves extensive lamina and facet joint resection. Eight patients who underwent PDC-SCLWA were included. The mean surgical duration was 290.6±59.2 minutes, with an average intraoperative blood loss of 775.0±389.7 mL. Intraoperative dural laceration occurred in two patients. All patients’ symptoms were alleviated, and no recurrent infection was observed during follow-up. Seven patients received double titanium meshes, and one received an iliac bone graft. At 3 months postoperatively, the fusion rates of intervertebral bodies and posterolateral laminae were 93.8% (15/16) and 100% (7/7), respectively. SIAVA is a severe postoperative complication, especially in elderly patients with multiple comorbidities. PDC-SCLWA is a safe and effective surgical technique. It provides advantages through posterior wall preservation that minimize spinal cord disruption, maintains mechanical stability, and optimizes the bone graft bed for fusion.

Objective To explore the feasibility and short-term clinical efficacy of single segment thora-columbar tuberculosis treated with one-stage posterior approach lamina-sparing decompression.Methods A total of 11 patients with single segment thoracolumbar tuberculosis who underwent one-stage posterior ap-proach preservation of vertebral plate lesion removal,bone graft fusion,and internal fixation treatment in this hospital from September 2021 to June 2022 were selected.C-reactive protein(CRP)and erythrocyte sedimen-tation rate(ESR)were monitored to evaluate tuberculosis bacteremia and activity control,visual analogue scale(VAS)score and Oswestry disability index(ODI)were followed up to evaluate the improvement of clin-ical function,and the American Spinal Injury Association(ASIA)injury scale was used to evaluate neurologi-cal function,and the correction of kyphosis was followed up.Results All 11 patients were fully followed up.The average surgical duration is(270.91±45.98)minutes,and the average surgical bleeding is(522.72± 194.11)mL.During the follow-up period,none of the 11 patients experienced tuberculosis recurrence,and all 11 patients achieved bone graft fusion.The fusion time was 6-9 months after surgery with an average of(7.36±1.12)months.Two patients with preoperative nerve damage recovered after surgery.During the fol-low-up period,11 patients did not experience any complications related to surgery.The average CRP,ESR,ODI score,and VAS score of postoperative patients decreased compared to preoperative levels,and further de-creased at 12 months after surgery;The patient's kyphosis caused by thoracolumbar tuberculosis was correc-ted,and no obvious angle loss was found at the last follow-up(P＞0.05).Conclusion One-stage posterior ap-proach lamina-sparing decompression is a safe and effective method for treating single segment thoracolumbar tuberculosis.

Objective:To investigate the potential mechanism of miR-1298-5p in non-small cell lung cancer(NSCLC)to regu-late the MSH2 gene and its effect on the biological behavior of tumor cells and the tumor immune microenvironment.Methods:Bioin-formatics was used to identify the key genes and miRNA involved in NSCLC.Cell proliferation was detected by CCK-8 assay,and cell invasion and migration were detected by Transwell assay.Levels of inflammatory factors were detected by ELISA assay.Western blot was used to measure the expression of MSH2 in cells,and fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to detect the expressions of miR-1298-5p and MSH2 gene in NSCLC cells.Dual luciferase reporter gene assay was performed to verify the targeting relationship between miR-1298-5p and MSH2.Spearman correlation analysis was performed to correlate miR-1298-5p with immune cells and immune factors in the tumor immune microenvironment.Results:The level of miR-1298-5p was down-regulated in NSCLC cells compared with normal lung tissue cells.miR-1298-5p overexpression inhibited the proliferation,migration and inva-sion of NSCLC cells.MSH2 was confirmed to be a target gene of miR-1298-5p using luciferase reporter gene assay.Furthermore,down-regulation of miR-1298-5p in NSCLC cells could be reversed by silencing MSH2.miR-1298-5p expression levels were negatively corre-lated with the levels of Treg,IL-10,and TGF-β,and positively correlated with the levels of CD3+T,CD4+T,CD8+T,NK cells,IL-2,and IFN-γ.Conclusion:miR-1298-5p negatively regulates MSH2 to inhibit the proliferation,invasion and migration of NSCLC cells and improve the tumor immune microenvironment.