Mastitis is one of the common and prevalent diseases in dairy cows,and the natural prod-uct daidzein is a kind of natural flavonoids with a wide range of pharmacological and anti-inflam-matory effects.However,the effect of daidzein on mastitis in dairy cows has not been reported.Therefore,in this study,we explored the effects of daidzein on LPS-induced inflammatory response and tight junction damage in dairy mammary epithelial cells Firstly,we pretreated the MAC-T cell line using different concentrations of daidzein,and it was clarified that daidzein below 200 μmol/L had no effect on the cell activity.Next,we examined the production of pro-inflammatory mediators in LPS-stimulated MAC-T cell lines using qRT-PCR,and clarified that daidzein could reduce the production of pro-inflammatory mediators in a concentration-dependent manner.Subsequently,af-ter the expression of Occludin,Claudin3 and ZO-1 was detected by immunofluorescence and West-ern Blot,it was clear that daidzein could alleviate MAC-T cell intercellular tight junction injury.Fi-nally,it was demonstrated that daidzein significantly inhibited LPS-induced activation of the NF-κB signaling pathway within MAC-T using network pharmacological analysis and Western Blot.The above results suggest that daidzein can inhibit LPS-induced inflammatory response and tight junc-tion damage in mammary epithelial cells of cows by suppressing the activation of NF-κB signaling pathway.The present study provides a theoretical basis for the alleviation of mastitis by natural products and further expands the pharmacological effects of daidzein.

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:To evaluate the effects of different volumes of ropivacaine for iliopsoas muscle plane block on quadriceps strength in patients undergoing hip arthroplasty.Methods:In this prospective study, 75 patients of either sex, aged 40-80 yr, with a body mass index of 18.5-30.0 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, undergoing elective hip arthroplasty from June to December 2023 at Baoding First Central Hospital, were randomized into 3 groups ( n=25 each) by using a computer-generated randomization sequence: ropivacaine 5 ml group (group Ⅰ), ropivacaine 10 ml group (group Ⅱ), and ropivacaine 15 ml group (group Ⅲ). Before induction of anesthesia, iliopsoas muscle plane block was performed with 0.5% ropivacaine 5, 10 and 15 ml in Ⅰ, Ⅱ and Ⅲ groups, respectively. The lateral femoral cutaneous nerve block was carried out using 0.5% ropivacaine 5 ml in all the three groups. The quadriceps muscle strength and status of quadriceps motor block in the affected limb were assessed on admission to postanesthesia care unit (PACU) and at 2, 4, 6, 24 and 48 h after surgery. The consumption of dezocine, score for patient′s satisfaction with analgesia, and occurrence of complications were recorded. Results:Compared with group Ⅰ, the quadriceps muscle strength scores were significantly decreased on admission to PACU and at 2, 4 and 6 h postoperatively in group Ⅲ, the rate of quadriceps motor block was significantly increased on admission to PACU in group Ⅱ, and the rate of quadriceps motor block was significantly increased on admission to PACU and at 2 and 4 h postoperatively in group Ⅲ ( P<0.05), and the consumption of dezocine was significantly decreased in group Ⅱ and group Ⅲ ( P<0.05). Conclusions:The recommended volume of ropivacaine for iliopsoas plane block is 10 ml in patients undergoing hip arthroplasty.

OBJECTIVES: To investigate the mechanism mediating the regulatory effect of miR-155-5p on proliferation of human submandibular gland epithelial cells (HSGECs) in primary Sjogren's syndrome (pSS). METHODS: Dual luciferase reporter assay was used to verify the targeting relationship between miR-155-5p and the PI3K/AKT pathway. In a HSGEC model of pSS induced by simulation with TRAIL and INF-γ, the effects of miR-155-inhibitor-NC or miR-155 inhibitor on cell viability, cell cycle, apoptosis and proliferation were evaluated using CKK8 assay, flow cytometry and colony formation assay. ELISA and RT-PCR were used to detect the expressions of inflammatory cytokines and miR-155-5p mRNA in the cells; Western blotting was performed to detect the expressions of proteins in the PI3K/AKT signaling pathway. RESULTS: Dual luciferase assay showed that miR-155-5p targets the PI3K/AKT pathway via PIK3R1 mRNA. The HSGEC model of pSS showed significantly decreased cell viability, cell clone formation ability and expressions IL-10 and IL-4 and increased cell apoptosis, cell percentage in G2 phase, expressions of TNF‑α, IL-6, miR-155-5p and PIK3R1 mRNA, p-PI3K/PI3K ratio, p-Akt/AKT ratio, and PIK3R1 protein expression. Treatment of the cell models with miR-155 inhibitor significantly increased the cell viability, G1 phase cell percentage, colony formation ability, and expressions of IL-10 and IL-4 levels, and obviously reduced cell apoptosis rate, G2 phase cell percentage, expressions of TNF-α, IL-6, miR-155-5p and PIK3R1 mRNA, p-PI3K/PI3K ratio, p-AKT/AKT ratio, and PIK3R1 protein expression. CONCLUSIONS In HSGEC model of pSS, inhibition of miR-155-5p can promote cell proliferation and reduced cell apoptosis by targeting PI3K1 mRNA to negatively regulate the overexpression of PI3K/AKT signaling pathway.
Humans ; MicroRNAs/genetics* ; Cell Proliferation ; Signal Transduction ; Proto-Oncogene Proteins c-akt/metabolism* ; Sjogren's Syndrome/pathology* ; Epithelial Cells/cytology* ; Submandibular Gland/cytology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Apoptosis ; Class Ia Phosphatidylinositol 3-Kinase ; Cells, Cultured

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*

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.

Mastitis is one of the common and prevalent diseases in dairy cows,and the natural prod-uct daidzein is a kind of natural flavonoids with a wide range of pharmacological and anti-inflam-matory effects.However,the effect of daidzein on mastitis in dairy cows has not been reported.Therefore,in this study,we explored the effects of daidzein on LPS-induced inflammatory response and tight junction damage in dairy mammary epithelial cells Firstly,we pretreated the MAC-T cell line using different concentrations of daidzein,and it was clarified that daidzein below 200 μmol/L had no effect on the cell activity.Next,we examined the production of pro-inflammatory mediators in LPS-stimulated MAC-T cell lines using qRT-PCR,and clarified that daidzein could reduce the production of pro-inflammatory mediators in a concentration-dependent manner.Subsequently,af-ter the expression of Occludin,Claudin3 and ZO-1 was detected by immunofluorescence and West-ern Blot,it was clear that daidzein could alleviate MAC-T cell intercellular tight junction injury.Fi-nally,it was demonstrated that daidzein significantly inhibited LPS-induced activation of the NF-κB signaling pathway within MAC-T using network pharmacological analysis and Western Blot.The above results suggest that daidzein can inhibit LPS-induced inflammatory response and tight junc-tion damage in mammary epithelial cells of cows by suppressing the activation of NF-κB signaling pathway.The present study provides a theoretical basis for the alleviation of mastitis by natural products and further expands the pharmacological effects of daidzein.

Objective:To evaluate the effects of different volumes of ropivacaine for iliopsoas muscle plane block on quadriceps strength in patients undergoing hip arthroplasty.Methods:In this prospective study, 75 patients of either sex, aged 40-80 yr, with a body mass index of 18.5-30.0 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, undergoing elective hip arthroplasty from June to December 2023 at Baoding First Central Hospital, were randomized into 3 groups ( n=25 each) by using a computer-generated randomization sequence: ropivacaine 5 ml group (group Ⅰ), ropivacaine 10 ml group (group Ⅱ), and ropivacaine 15 ml group (group Ⅲ). Before induction of anesthesia, iliopsoas muscle plane block was performed with 0.5% ropivacaine 5, 10 and 15 ml in Ⅰ, Ⅱ and Ⅲ groups, respectively. The lateral femoral cutaneous nerve block was carried out using 0.5% ropivacaine 5 ml in all the three groups. The quadriceps muscle strength and status of quadriceps motor block in the affected limb were assessed on admission to postanesthesia care unit (PACU) and at 2, 4, 6, 24 and 48 h after surgery. The consumption of dezocine, score for patient′s satisfaction with analgesia, and occurrence of complications were recorded. Results:Compared with group Ⅰ, the quadriceps muscle strength scores were significantly decreased on admission to PACU and at 2, 4 and 6 h postoperatively in group Ⅲ, the rate of quadriceps motor block was significantly increased on admission to PACU in group Ⅱ, and the rate of quadriceps motor block was significantly increased on admission to PACU and at 2 and 4 h postoperatively in group Ⅲ ( P<0.05), and the consumption of dezocine was significantly decreased in group Ⅱ and group Ⅲ ( P<0.05). Conclusions:The recommended volume of ropivacaine for iliopsoas plane block is 10 ml in patients undergoing hip arthroplasty.

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.