Endothelial dysfunction induced by inflammation and oxidative stress represents a critical pathological mechanism in cardiovascular and cerebrovascular diseases, including sepsis and atherosclerosis. Although crebanine has been reported to possess antiinflammatory and analgesic properties, its effects on inflammation and oxidative stress in endothelial cells remain unknown. In this study, we assessed cell viability, apoptosis, and migration using the Cell Counting Kit-8 (CCK-8), flow cytometry, and a wound healing assay, respectively. The levels of reactive oxygen species (ROS) and the expression of inflammatory and oxidative stress markers were determined by qRT-PCR, enzyme-linked immunosorbent assay (ELISA), and Western blotting analysis. Our results demonstrated that crebanine alleviated lipopolysaccharide (LPS)-induced apoptosis and dysfunction in human umbilical vein endothelial cells (HUVECs). Crebanine treatment inhibited the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), ROS, and malondialdehyde (MDA), while it enhanced the activity of the antioxidant enzyme superoxide dismutase (SOD). Mechanistically, crebanine suppressed LPS-induced activation of the NF-κB signaling pathway in HUVECs. Furthermore, the improvement effect of crebanine on the inflammation and dysfunction in LPS-treated HUVECs was reversed by diprovocim, an NF-κB activator.These findings suggest that crebanine ameliorates LPS-induced inflammation and oxidative stress in HUVECs by inhibiting the NF-κB signaling pathway, indicating its potential therapeutic value for treating vascular endothelial dysfunction-related diseases.

Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

Background: This study was performed to characterize the incidence, costs, and risk factors associated with renal and cardiovascular adverse outcomes following primary percutaneous coronary intervention (pPCI) in patients with ST-elevation myocardial infarction (STEMI). Methods: Patients with STEMI who underwent pPCI using iso-osmolar contrast were enrolled at 39 centers. The incidence of acute kidney injury (AKI) and major adverse renal and cardiovascular events (MARCE) was analyzed, as well as inpatient costs. Logistic regression analysis was performed to identify risk factors. Results: Among 2,293 patients, the incidence of AKI and MARCE within 72 hours post-pPCI was 4.14% (n = 95) and 4.40% (n = 101), respectively. AKI and/or MARCE were associated with systolic blood pressure (AKI: odds ratio [OR], 1.009; 95% confidence interval [CI], 1.000–1.018), hypertension (AKI: OR, 1.815; 95% CI, 1.133–2.906; MARCE: OR, 1.760;95% CI, 1.118–2.769), anterior wall infarction (AKI: OR, 1.895; 95% CI, 1.196–3.004; MARCE:OR, 1.939; 95% CI, 1.240–3.032), Killip class (AKI: OR, 1.465; 95% CI, 1.117–1.922; MARCE:OR, 1.467; 95% CI, 1.131–1.903), and serum creatinine (SCr; MARCE: OR, 1.006; 95% CI, 1.000–1.012). Hospitalization costs for patients with STEMI who developed AKI or MARCE were significantly higher than for those without AKI (9,595 ± 5,795 vs. 8,279 ± 3,872 USD, P = 0.003) or without MARCE (9,890 ± 5,616 vs. 8,255 ± 3,859 USD, P < 0.001). Conclusions In patients with STEMI undergoing pPCI with iso-osmolar contrast, the incidence of AKI and MARCE was associated with higher hospitalization costs. Systolic blood pressure, hypertension, anterior wall infarction, Killip class, and SCr were identified as risk factors for these outcomes.

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.

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective:To investigate the differential expression profiles of long non-coding RNAs(LncRNAs) and messenger RNAs(mRNAs) regulated by soluble dipeptidyl peptidase-4(sDPP4) during vascular smooth muscle cell calcification, and to explore the potential underlying calcification mechanisms.Methods:DPP4 levels in blood vessels and peripheral blood of diabetic patients were measured using Western blotting(WB) and real-time quantitative PCR(RT-qPCR). A cellular calcification model was established by treating human aortic vascular smooth muscle cells(HASMCs) with sDPP4. The effects of sDPP4 on HASMCs were assessed by WB, RT-qPCR, alizarin red staining, and calcium content determination. High-throughput sequencing was performed to analyze the differential expression profiles of LncRNA and mRNA following sDPP4 treatment. Among them, LncRNA ENST00000540293, which exhibited the most pronounced downregulation and was located adjacent to the matrix metalloproteinase-1(MMP-1) gene, was selected for further investigation. The osteogenic transdifferentiation of HASMCs after silencing LncRNA ENST00000540293 was evaluated using WB, RT-qPCR, alizarin red staining, and immunofluorescence-based cytoskeletal staining.Results:DPP4 expression was significantly elevated in both blood vessels and peripheral blood of diabetic patients. sDPP4 stimulation upregulated the protein levels of osteopontin(OPN) and runt-related transcription factor 2(RUNX2) in HASMCs, enhanced alizarin red staining, and increased intracellular calcium deposition. RNA sequencing revealed significant downregulation of LncRNA ENST00000540293 following sDPP4 exposure, while GO and pathway analysis indicated a marked increase in extracellular matrix binding activity(GO: 0050840). Silencing LncRNA ENST00000540293 suppressed α-smooth muscle actin(α-SMA) expression, promoted OPN and RUNX2 expression, increased calcification as shown by positive alizarin red staining, and cytoskeletal staining demonstrated osteogenic transdifferentiation of HASMCs, accompanied by a significant rise in MMP-1 protein level.Conclusion:sDPP4 promotes osteogenic transdifferentiation of HASMCs, potentially by downregulating LncRNA ENST00000540293. MMP-1 may be a potential target regulated by LncRNA ENST00000540293.

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

Objective:To investigate the differential expression profiles of long non-coding RNAs(LncRNAs) and messenger RNAs(mRNAs) regulated by soluble dipeptidyl peptidase-4(sDPP4) during vascular smooth muscle cell calcification, and to explore the potential underlying calcification mechanisms.Methods:DPP4 levels in blood vessels and peripheral blood of diabetic patients were measured using Western blotting(WB) and real-time quantitative PCR(RT-qPCR). A cellular calcification model was established by treating human aortic vascular smooth muscle cells(HASMCs) with sDPP4. The effects of sDPP4 on HASMCs were assessed by WB, RT-qPCR, alizarin red staining, and calcium content determination. High-throughput sequencing was performed to analyze the differential expression profiles of LncRNA and mRNA following sDPP4 treatment. Among them, LncRNA ENST00000540293, which exhibited the most pronounced downregulation and was located adjacent to the matrix metalloproteinase-1(MMP-1) gene, was selected for further investigation. The osteogenic transdifferentiation of HASMCs after silencing LncRNA ENST00000540293 was evaluated using WB, RT-qPCR, alizarin red staining, and immunofluorescence-based cytoskeletal staining.Results:DPP4 expression was significantly elevated in both blood vessels and peripheral blood of diabetic patients. sDPP4 stimulation upregulated the protein levels of osteopontin(OPN) and runt-related transcription factor 2(RUNX2) in HASMCs, enhanced alizarin red staining, and increased intracellular calcium deposition. RNA sequencing revealed significant downregulation of LncRNA ENST00000540293 following sDPP4 exposure, while GO and pathway analysis indicated a marked increase in extracellular matrix binding activity(GO: 0050840). Silencing LncRNA ENST00000540293 suppressed α-smooth muscle actin(α-SMA) expression, promoted OPN and RUNX2 expression, increased calcification as shown by positive alizarin red staining, and cytoskeletal staining demonstrated osteogenic transdifferentiation of HASMCs, accompanied by a significant rise in MMP-1 protein level.Conclusion:sDPP4 promotes osteogenic transdifferentiation of HASMCs, potentially by downregulating LncRNA ENST00000540293. MMP-1 may be a potential target regulated by LncRNA ENST00000540293.

Objective To explore the effect and mechanism of knockdown of mitochondrial transcription factor A(TFAM)on the growth of gastrointestinal stromal tumor(GIST)cells mediated by tumor-associated macrophages(TAMs)polarization.Methods Human acute leukemia mononuclear macrophage cell line THP-1 induced by phobate and interleukin(IL)-4 was used to establish TAMs,lentivirus shRNA TFAM and negative control shRNA NC were transfected into TAMs,which were recorded as TAMs+sh-TFAM group and TAMs+sh-NC group,respectively,the untransfected cells were recorded as the TAMs group.The mRNA expression of TFAM,IL-10 and arginase-1(Arg-1)was detected by qRT-PCR.The TFAM protein expression was detected by Western blot.The expression level of CD206 was detected by flow cytometry.The human GIST cell line GIST-T1 were divided into GIST-T1 group,TAMs+GIST-T1 group,TAMs+sh-NC+GIST-T1 group,TAMs+sh-TFAM+GIST-T1 group,and treated with fresh medium containing different TAMs culture supernatants.The cell proliferation and apoptosis levels were detected by CCK-8,EdU staining and Annexin V-FITC/PI double staining respectively.Results Compared with TAMs group and TAMs+sh-NC group,the TFAM mRNA and protein expression levels of THP-1 cells in TAMs+sh-TFAM group were significantly down-regulated(P<0.05).Compared with control group,the expression levels of CD206 and IL-10 and Arg-1 mRNA of THP-1 cells in TAMs group were significantly increased(P<0.05).Compared with TAMs+sh-NC group,the expression levels of CD206 and IL-10 and Arg-1 mRNA of THP-1 cells in TAMs+sh-TFAM group were significantly decreased(P<0.05).Compared with GIST-T1 group,the proliferative activity of GIST-T1 cells and EdU positive cells rate in TAMs+GIST-T1 group were significantly increased(P<0.05),while the apoptosis rate was significantly decreased(P<0.05).Compared with TAMs+sh-NC+GIST-T1 group,the proliferative activity of GIST-T1 cells and EdU positive cells rate in TAMs+sh-TFAM+GIST-T1 group were significantly decreased(P<0.05),while the apoptosis rate was significantly increased(P<0.05).Conclusion Knockdown of TFAM can inhibit the polarization of TAMs to M2 phenotype,thus inhibiting the proliferation of GIST cells,promoting cell apoptosis,and preventing the progression of GIST.