Surgical therapy of supravalvular aortic stenosis (SVAS) is associated with low overall early mortality but high incidence of postoperative adverse cardiac events. The aims of this study were to develop and validate a predictive model for major adverse cardiovascular events (MACE) in patients undergoing surgical repair of SVAS. This study included 262 patients who underwent surgical repair of SVAS between 2002 and 2019 in Beijing and Yunnan, China. MACE occurred during postoperative hospitalization or within 30 days after SVAS repair. Multivariate logistic regression was used to select prognostic factors for MACE and construct a nomogram. The receiver operating characteristic curve (ROC), calibration curve and decision curve analysis (DCA) were used to assess the predictive performance of the nomogram. Age, sex, body surface area, cardiopulmonary bypass time, and aortic valve z score were identified as prognostic factors. These five prognostic factors were used to construct the prediction nomogram. The area under the curve of the model was 0.859 (95

BACKGROUND:Metabolic disturbances are key contributors to myocardial ischemia-reperfusion (I/R) injury, yet the underlying molecular mechanisms remain largely unclear. Rho family GTPase 3 (RND3), a cytosolic small guanosine triphosphatase (GTPase) known to antagonize ROCK1 (Rho-associated coiled-coil kinase 1), has been implicated in several cardiovascular disorders. However, its mitochondrial localization and functional role in cardiac energy metabolism and I/R injury remain unknown. METHODS:A murine model of myocardial I/R injury was established through left anterior descending coronary artery ligation. Mice with cardiomyocyte-specific knockout and overexpression of Rnd3 were generated. To investigate the role of RND3 in cardiac metabolism and I/R injury, we used 13C-nuclear magnetic resonance, 18F-fluorodeoxyglucose positron emission tomography/computed tomography scanning, seahorse mitochondrial energy metabolism assays, and 13C-metabolic flux tracing. Mechanistic studies were conducted using RNA sequencing, coimmunoprecipitation, mass spectrometry, and glutathione S-transferase (GST) pulldown assays. RESULTS:Cardiomyocyte-specific deletion of Rnd3 (Rnd3 conditional knockout, Rnd3cKO) resulted in impaired glucose oxidation and compensatory upregulation of fatty acid oxidation, leading to pronounced cardiac dysfunction and increased mortality. Rnd3cKO hearts exhibited reduced pyruvate/malate-driven complex I respiration and marked uncoupling between glycolysis and the tricarboxylic acid cycle. Mechanistically, RND3 was identified as a novel mitochondrial matrix-localized small GTPase that directly binds to ACAT1 (acetyl-coenzyme A [CoA] acetyltransferase), disrupting its interaction with PDHA1 (pyruvate dehydrogenase E1α subunit) and thereby promoting PDHA1 acetylation and glucose oxidation. It is important to note that RND3 expression was significantly downregulated in both human and murine hearts after I/R insult. Loss of RND3 sensitized the hearts to I/R injury, as evidenced by reduced levels of phosphocreatine and ATP. Conversely, cardiac-specific overexpression of Rnd3 conferred protection against I/R injury, an effect that was abolished upon Pdha1 knockdown. CONCLUSIONS:Our results identify RND3 as a novel mitochondria-localized regulator of glucose oxidation that safeguards the heart against I/R injury. Therapeutic reconstitution of Rnd3 may represent a promising strategy to restore metabolic homeostasis and mitigate myocardial damage in the context of I/R.

The pathogenic mechanism underlying diseases caused by mitochondrial DNA (mtDNA) mutation, including hypertension, persists as an unresolved global challenge. Although mutation-induced mitochondrial defects have been well characterized, how these mito-perturbations are converted into critical intermediary signaling cascades and contribute to diseases remain unknown. Here, using human induced pluripotent stem cell (hiPSC)-derived vascular organoids (VOs) and vascular cells, the hypertensive mt. tRNAIle4263A > G mutation was identified to induce vascular senescence, apoptosis and vascular-specific dysfunction through mitochondria-endoplasmic reticulum (ER) interaction. For the first time, this study mapped the transcriptional reprogramming landscape of human VOs carrying this mutation. Through systematic screening and functional validation, ER stress was screened out, together with downstream mitochondria-associated ER membranes-mitochondrial Ca2+ overload resulting in vascular abnormality. Pathological reactive oxygen species (ROS) elevation, driven by tRNAIle destabilization and bioenergetic failure, acts as the primary instigator of maladaptive ER stress activation in this cascade. Pharmacological targeting of this axis-using mito-Tempol (a mitochondria-targeted ROS scavenger), Tauro Ursodeoxycholic Acid (an ER stress inhibitor), or RU265 (a highly-selective mitochondrial calcium uniporter inhibitor)-rescues vascular abnormality. This study highlights mt. tRNAIle4263A > G mutation orchestrates vascular pathology through ROS induced activation of inter-organelle communication, resolving a long-standing knowledge gap between mtDNA mutations and diseases and establishing therapeutic nexuses for mtDNA mutation-related cardiovascular diseases.

Objective To investigate the association between the weight-to-waist ratio and total bone mineral density in US adults. Methods This cross-sectional study included 7005 adults from the National Health and Nutrition Examination Survey 2011–2018. The weight-to-waist ratio was calculated as body weight divided by waist circumference, and total bone mineral density was measured using dual-energy X-ray absorptiometry. Survey-weighted multivariable linear regression and restricted cubic spline analyses were conducted to evaluate the association between the weight-to-waist ratio and total bone mineral density after adjustment for demographic, socioeconomic, lifestyle, and clinical covariates. Results A higher weight-to-waist ratio was significantly associated with greater total bone mineral density across all models. In the fully adjusted model, each 1-unit increase in the weight-to-waist ratio was associated with a 0.39 g/cm 2 increase in total bone mineral density (95% confidence interval: 0.35–0.42; P < 0.001). Participants in the highest weight-to-waist ratio quartile had significantly higher total bone mineral density than those in the lowest quartile (β = 0.09, 95% confidence interval: 0.08–0.10; P < 0.001). Restricted cubic spline analysis indicated a significant positive linear association. The association was stronger in men than in women (P for interaction <0.001). Conclusions A higher weight-to-waist ratio was independently associated with greater total bone mineral density in US adults, particularly among men. The weight-to-waist ratio may provide complementary anthropometric information regarding skeletal health, although prospective studies are needed to confirm causality.

BackgroundHepatocellular carcinoma (HCC), the predominant pathological subtype of primary liver cancer, remains a major global health burden with poorly defined molecular mechanisms. Cell growth regulator 11 (CGR11), a novel secreted protein characterized by EF-hand motifs, has recently emerged as a potential extracellular signaling modulator in tumor biology. Although implicated in cancer cell proliferation and metastasis, its precise role and regulatory mechanisms in HCC progression have not been elucidated.MethodsWe integrated bioinformatics analysis with single-cell transcriptomic profiling and CellChat-based intercellular communication mapping. CGR11 expression and localization were validated in tissue microarrays, HCC cell lines, and tumor specimens using immunohistochemical staining, qRT-PCR, and Western blotting. In vitro experiments and both subcutaneous and orthotopic xenograft models were established to evaluate the biological effects of CGR11 overexpression and knockdown. RNA sequencing, LC3 fluorescence assay, and transmission electron microscopy were conducted to elucidate the underlying molecular mechanism.ResultsCGR11 expression was markedly increased in HCC tissues relative to adjacent non-tumorous liver tissues and correlated with poor patient prognosis. Functional and mechanistic analyses demonstrated that CGR11 promotes HCC cell proliferation, invasion and tumor growth by inhibiting autophagy levels through activation of the PI3K/AKT signaling. Conversely, CGR11 knockdown restored autophagy and significantly suppressed tumor progression in both cellular and animal models.ConclusionOur findings establish CGR11 as a novel oncogenic regulator that contributes to HCC progression by suppressing autophagy via PI3K/AKT activation. Targeting the CGR11-PI3K/AKT axis may therefore provide a promising avenue for precision therapeutic intervention in HCC.

INTRODUCTION:Senescent mesenchymal stem cells (MSCs) exhibit impaired self-renewal, limiting their therapeutic potential. While multi-omics have revealed downregulation of pan-tissue Fbn1 with aging, particularly in MSCs, the role of its derivative asprosin in MSC senescence is unknown. OBJECTIVES:To elucidate the regulation of senescence/reparative function in aged MSCs by asprosin and evaluate its therapeutic potential for aged MSC-mediated cardiac repair after myocardial infarction (MI). METHODS:Serum asprosin levels were measured by enzyme-linked immunosorbent assay, and asprosin expression in MSCs was determined by western blotting. Fbn1 expressiondynamics with aging were assessed using public transcriptomic/single-cell datasets. Gain/loss-of-function (lentiviral overexpression/CRISPR-Cas9 knockout) studies were employed to validate the role of asprosin. The effects of recombinant asprosin on senescent MSC proliferation, migration, and pro-angiogenic secretion were tested. Glycolytic flux (Seahorse), metabolites (glucose uptake, G-6-P, lactate), and lactylation (pan-lysine, H3K18la) were measured. Integrated H3K18la CUT&Tag/RNA-seq was performed to identify downstreamtargets, and therapeutic efficacy was assessed in an MI mouse model using intramyocardial injection of asprosin-overexpressing aged MSCs. RESULTS:Circulating asprosin was correlated with adipose mass in young obese mice but was attenuated in aged obese mice. Consistently, human cohorts (normal body mass index) showed an inverse age-asprosin correlation. Systemic and MSC-specific asprosin expression significantly declined with aging. Asprosin knockout intensified H2O2-induced MSC acute premature senescence, whereas its overexpression restored MSC self-renewal. Human recombinant asprosin protein (requiring post-translational modifications for bioactivity) enhanced proliferation, migration, and paracrine angiogenesis in senescent MSCs. Mechanistically, asprosin activated the PI3K/Akt-HIF-1 pathway to upregulate VEGF/TIMP1 (angiogenesis) and drive the glycolysis-lactate-H3K18la axis (proliferation/migration). H3K18la CUT&Tag/RNA-seq identified targets regulating DNA repair, proliferation, and migration. Asprosin deficiency impaired DNA repair. In MI mice, asprosin-overexpressing aged MSCs significantly improved retention and left ventricular ejection fraction, attenuated cardiac remodeling, and promoted peri-infarct angiogenesis. CONCLUSION:Asprosin is a novel MSC-specific rejuvenation factor that antagonizes senescence through metabolic-epigenetic interplay. Targeting the asprosin-driven "Glycolysis-Lactylation-Epigenetics" axis offers a transformative strategy to enhance MSC-based therapies for ischemic heart disease.

ABSTRACT Background Robust longitudinal studies evaluating the association between the C‐reactive protein–triglyceride–glucose index (CTI) and cardiometabolic multimorbidity (CMM) are scarce. To better understand the clinical value of the CTI, this study was conducted to explore the association of the CTI with CMM risk and progression, and to compare its predictive performance with indices incorporating central obesity. Methods This cohort study analyzed data from the China Health and Retirement Longitudinal Study spanning 2011–2020, including 9477 participants. The associations of the CTI, triglyceride–glucose (TyG), TyG–waist circumference (TyG–WC), and TyG‐waist‐to‐height ratio with CMM incidence were assessed using multivariable Cox regression. Predictive performance was compared using the area under the receiver operating characteristic curve (AUC), net reclassification index (NRI), and integrated discrimination improvement (IDI). Multi‐state models were used to analyze disease‐stage transitions. Results During follow‐up, 462 participants developed CMM. After full adjustment, a 1‐standard deviation increase in the CTI was associated with a 41% higher CMM risk (hazard ratio [HR]: 1.41, 95% confidence interval [CI]: 1.17–1.69). In direct comparison, TyG–WC showed the highest predictive AUC (0.704, 95% CI: 0.678–0.730). Adding the CTI to a conventional risk model significantly improved the NRI and IDI. Multistate modeling demonstrated that the CTI was associated with the progression from baseline health to diabetes mellitus, stroke, and heart disease, with a stronger association observed for diabetes mellitus (HR: 1.47, 95% CI: 1.36–1.60). Conclusions The CTI independently predicted CMM risk and progression. Although the TyG–WC index demonstrated superior predictive performance, the CTI remains a clinically convenient, blood‐based composite marker that captures the insulin resistance–inflammation pathway, offering a valuable tool for risk stratification.

Objective Intestinal ischemia-reperfusion(IR)injury is a common and critical pathological process in clinical practice.Ferroptosis,a form of cell death characterized by iron-dependent accumulation of uncontrolled lipid peroxidation,has been confirmed to be involved in intestinal IR injury.Nuclear factor erythroid 2-related factor 2(Nrf2)is a key molecule in regulating ferroptosis,and its activation can inhibit this form of cell death,thereby alleviating tissue injury.Sulforaphane(SFN),a classical Nrf2 activator,exerts antioxidant protective effects.This study aims to investigate whether SFN alleviates intestinal IR injury by activating the Nrf2 pathway to inhibit ferroptosis.Methods ① SFN-related target genes,ferroptosis-related genes,and intestinal IR injury-related genes were retrieved and integrated from online databases,including TCMSP,GeneCards and OMIM,and the intersection genes were identified and presented in a Venn diagram.Then the intersection genes were imported into STRING to construct a protein-protein interaction(PPI)network,and topological analysis was performed using Cytoscape(v3.9.1)to screen core targets.Molecular docking was employed to predict the binding affinity between SFN and the key target Nrf2.② Twenty-four SPF-grade male C57BL/6 mice(6 to 8 weeks old,weighing 22±2 g)were randomly divided into 4 groups(n=6):Sham group,IR group,IR+SFN group,and IR+SFN+ML385(a specific Nrf2 inhibitor)group.Except for the Sham group,the other groups were inflicted with clamping the superior mesenteric artery for 45 min followed by reperfusion for 30 min to establish an IR injury model.The IR+SFN and IR+SFN+ML385 groups were given an intraperitoneal injection of SFN(5 mg/kg)1 h before clamping,while the IR+SFN+ML385 group additionally received intraperitoneal injection of ML385(30 mg/kg)2 h before clamping.After 30 min of reperfusion,small intestinal tissues were harvested.Histopathological changes were observed by light microscopy after HE staining,and the severity of intestinal injury was evaluated using Chiu's score.Levels of malondialdehyde(MDA),superoxide dismutase(SOD),and reduced glutathione(GSH)were measured using biochemical reagent kits.Western blotting was performed to detect the protein expression of acyl-CoA synthetase long-chain family member 4(ACSL4),glutathione peroxidase 4(GPX4),Nrf2,and heme oxygenase-1(HO-1).Results ① Network pharmacology analysis identified 162 SFN target genes,2 772 ferroptosis-related genes,and 2 100 intestinal IR injury-related genes,with 43 intersection genes.PPI network topological analysis revealed 36 core genes,including Nrf2.Molecular docking showed that SFN could form a binding conformation with Nrf2,with a binding energy of-3.3 kcal/mol.② In vivo results demonstrated that compared with the Sham group,the IR group exhibited significantly aggravated intestinal mucosal injury,as evidenced by an increased Chiu's score(P＜0.05),elevated MDA level,and decreased SOD and GSH activities(P＜0.05).Meanwhile,the expression of GPX4 was downregulated while that of ACSL4 was upregulated(P＜0.05),suggesting the occurrence of ferroptosis in intestinal IR.SFN pretreatment ameliorated the above pathological and biochemical changes,upregulated Nrf2 and HO-1 expression(P＜0.05),restored GPX4 expression and downregulated ACSL4 expression(P＜0.05).The protective effects of SFN and its regulatory effects on the Nrf2/HO-1 axis and ferroptosis-related proteins were partially reversed by the addition of ML385(P＜0.05).Conclusion SFN can alleviate intestinal IR injury,and its effect may be related to enhancing the antioxidant response associated with the Nrf2/HO-1 signaling axis and ameliorating ferroptosis-related molecular changes.

ABSTRACT Hypoalbuminemia is a recognized risk factor for postoperative pulmonary complications (PPCs), but whether preoperative albumin infusion improves pulmonary outcomes after cardiac surgery remains unclear. In this single‐center, randomized, double‐blind, controlled pilot trial (ChiCTR2300076609), 80 elderly patients with preoperative albumin concentrations <40 g/L who underwent elective cardiac surgery with cardiopulmonary bypass were randomly assigned to receive 100 mL of 20% albumin (40 patients) or saline before surgery (40 patients). The primary outcomes were PPC severity and incidence during hospitalization, and perioperative immune cell changes were also explored. All randomized participants completed the trial. Compared with the controls, the patients in the albumin group had lower PPC severity (median [IQR], 1 [1–2] vs. 2 [2–3]; mean difference, −0.75; 95% CI, −1.15 to −0.35; p = 0.001) and a lower incidence of PPCs (30% vs. 57.5%; risk difference, −0.275; 95% CI, −0.48 to −0.07; p = 0.013). Additionally, the Th17 cell proportion and γδTreg cell proportion were significantly decreased and increased, respectively, in the albumin group after surgery (p < 0.001). These findings suggest that preoperative albumin supplementation may reduce PPC risk and modulate immune responses, warranting confirmation in larger multicenter trials.

BACKGROUND:While elevated fibrinogen-to-albumin ratio (FAR) correlates with all-cause mortality in adults, its prognostic value in pediatric intensive care units (PICUs) remains unclear. This study aimed to investigate the association between FAR and in-hospital all-cause mortality in critically ill pediatric patients. METHODS:We conducted a retrospective cohort study analyzing the PIC database from 2010 to 2018. Blood samples for fibrinogen and serum albumin were collected within 24 h of admission. The primary outcome was 28-day all-cause mortality. We utilized multivariable Cox proportional hazards regression, smooth curve fitting, and Kaplan-Meier survival curves, along with subgroup analyses and a two-piecewise linear regression model to assess associations. RESULTS:A total of 5,087 patients (mean age 1.4 years; 44.7% female) were included. The 28-day mortality rate was 4.7% (240/5,087). FAR was independently associated with mortality risk (HR: 0.83, 95% CI: 0.70-0.98; P = 0.031). Higher FAR tertiles correlated with decreased mortality risk (HR: 0.66, 95% CI: 0.44-1.00; P = 0.005). The FAR-mortality relationship was L-shaped, with a threshold around 0.648. The effect sizes on the left and right sides of the inflection point were 0.076 (95% CI: 0.025-0.234, P < 0.001) and 1.126 (95% CI: 0.669-1.895, P = 0.656), respectively. No significant interactions were observed between FAR and 28-day mortality, except in patients with malignant cancer (P for interaction > 0.05). The results of the sensitivity analysis remained stable. CONCLUSIONS:This study reveals an L-shaped relationship between FAR and 28-day in-hospital all-cause mortality in PICU patients, suggesting that FAR may serve as a prognostic marker for mortality in critically ill children.

Cholangiocarcinoma (CCA), which is a malignant tumor originating from the epithelial cells of the bile ducts, has witnessed an increasing incidence year by year. Owing to the dearth of effective treatments, the prognosis for CCA is rather poor. Isorhamnetin is known to possess anti-tumor, anti-inflammatory and oxidative stress modulating effects; however, its role in CCA remains unclear. Firstly, we screened the core targets and pathways of isorhamnetin for the treatment of CCA through a network pharmacology approach. Subsequently, we verified via molecular docking that the core targets could dock stably with isorhamnetin. Finally, we verified the inhibitory effect of isorhamnetin on the malignant biological behavior of CCA in vitro and in vivo experiments. Based on the network pharmacology analysis, we came to the conclusion that AKT1 might be a core target of isorhamnetin in the treatment of CCA. Molecular docking indicated that AKT1 was capable of binding stably to isorhamnetin. Subsequently, In vitro experiments demonstrated that isorhamnetin was able to suppress the proliferation and metastasis of CCA cells, and AKT1 played a pivotal role in this process. Mechanistically speaking, isorhamnetin exerts its inhibitory effect on tumor growth via the PI3K/AKT signaling pathway. Our study demonstrated for the first time that isorhamnetin can inhibit the progression of CCA through PI3K/AKT, and that AKT1 may be a target of isorhamnetin for the treatment of CCA.

BackgroundPatients who underwent surgical repair of supravalvular aortic stenosis (SVAS) are at high risk for postoperative major adverse cardiovascular events (MACE). This study aimed to investigate the association between cardiopulmonary bypass (CPB) duration and MACE occurring during postoperative hospitalization or within 30 days post-surgery.MethodsPatients who underwent surgical repair of SVAS from 2002 to 2019 at Beijing Fuwai Hospital and Yunnan Fuwai Hospital were included in this study. Patients were stratified into “CPB duration >2 h” and “CPB duration ≤2 h” groups based on intraoperative CPB duration. Various statistical methodologies were employed to investigate the association between CPB duration and early postoperative MACE, including multivariate adjustment, propensity score adjustment, propensity score matching, and logistic regression based on propensity score weighting.Results297 participants were included and 164 were finally matched. In the propensity score-matched cohort, CPB duration was positively associated with early postoperative MACE (odds ratio = 18.13; 95% confidence interval 2.33–140.86; P = 0.006). Consistent results were obtained in the Inverse probability of treatment-weighted, standardized mortality ratio-weighted, pairwise algorithmic-weighted, and overlap-weighted models.ConclusionPatients with CPB duration >2 h were at a higher risk of early postoperative MACE compared to those with CPB duration ≤2 h. This emphasized the significance of minimizing CPB exposure for the prognosis of patients with SVAS.

Rationale: Myocardial ischemia reperfusion (I/R) injury is a major cause of adverse outcomes following revascularization therapy. Although alterations in metabolic activities during reperfusion have been implicated, the molecular mechanisms underlying the pathogenesis of I/R injury remain elusive. Metaxin 2 (MTX2), initially identified as a core component of protein import complexes, has recently been characterized in diverse cellular functions. Nevertheless, its involvement in myocardial I/R injury has yet to be fully elucidated. In this study, we aim to evaluate the role and the underlying mechanism of MTX2 in I/R injury. Methods: The myocardial I/R model was established, and the protein levels of MTX2 were determined at different time points following coronary occlusion. Loss-of-function and gain-of-function strategies were applied via genetic ablation or intra-myocardial adenovirus injection to ascertain the role of MTX2 in myocardial I/R injury. RNA sequencing, seahorse metabolic analysis, and mass spectrometry were conducted to uncover the underlying molecular mechanisms. Results: We observed that the expression of MTX2 was significantly decreased in I/R hearts. Tamoxifen-induced cardiomyocyte-specific deletion of Mtx2 led to aggravated myocardial I/R injury, resulting in impaired cardiac oxidative phosphorylation and glycolysis. Mechanistically, dimeric PKM2, a less active pyruvate kinase form compared with tetrameric PKM2, was found to be dramatically accumulated in Mtx2 deficiency mice after myocardial I/R surgery. The TOM37 domain of MTX2 interacted directly with PKM2 to promote PKM2 tetramerization, thereby modulating glucose metabolic flux. Pharmacological activation of PKM2 by a small-molecule PKM2 activator, TEPP-46, rescued the metabolic and functional outcomes of I/R in Mtx2 deficiency mice. Conclusions: Our results identified, for the first time, a cardioprotective role of MTX2 in modulating cardiac glucose metabolism by facilitating PKM2 tetramerization. Targeting metabolic homeostasis by restoring MTX2 might be a promising therapeutic strategy to mitigate myocardial I/R injury.

Background ​ ​ While peripheral artery disease (PAD) is an established risk factor for long-term mortality in stable coronary artery disease (CAD) patients following percutaneous coronary intervention (PCI), its predictors and impact on a broader range of clinical outcomes require further investigation.​ ​ Methods ​ ​ This study enrolled 204 consecutive patients with newly diagnosed stable CAD undergoing PCI at Shinonoi General Hospital between October 2014 and October 2017. The association between PAD and 4-year outcomes—including all-cause death (ACD), the composite of ACD, non-fatal myocardial infarction (MI), and stroke (ACD-MI-Stroke), the composite of cardiac death (CD), non-fatal MI, and stroke (CD-MI-Stroke), and stroke alone—was assessed using inverse probability of treatment weighting (IPTW) and adjusted Kaplan-Meier curves.​ ​ Results ​ ​ Multivariable analysis identified diabetes mellitus (DM), dyslipidemia (DLP), old cerebral infarction (OCI), coronary ostial lesions, and high triglycerides (TG) as independent predictors of PAD. For the ACD-MI-Stroke endpoint, IPTW analysis demonstrated that PAD was consistently associated with a significant, approximately threefold increased risk (hazard ratio [HR]: 3.0-3.2), with narrow confidence intervals and sustained significance (p ≤ 0.008). Although the association between PAD and ACD was of borderline significance in the unadjusted model (HR: 2.51, 95% confidence interval [CI]: 0.93–6.74), IPTW adjustment revealed a robust and consistently significant threefold risk (HR ≈ 3.0-3.1, p ≤ 0.047). For the CD-MI-Stroke endpoint, the statistical precision of the PAD effect was attenuated with the inclusion of more covariates. Moreover, adjusted Kaplan-Meier curves consistently showed a lower survival probability for patients with PAD across all four outcomes over the 4-year follow-up.​ ​ Conclusions ​ ​ In CAD patients undergoing PCI, PAD independently and substantially increases the risk of multiple adverse outcomes, notably ACD, stroke and combinations involving them. DM, DLP, OCI, coronary ostial lesions, and elevated TG levels were identified as significant risk factors for the presence of PAD.

BACKGROUND:To assess the midterm efficacy and safety of drug-coated balloons (DCBs) compared with standard percutaneous transluminal angioplasty (PTA) in the treatment of femoropopliteal artery in-stent restenosis in the AcoArt I trial. METHODS:The AcoArt I trial was a prospective, multicentered, randomized clinical study of 50 patients with femoropopliteal artery in-stent restenosis treated with either paclitaxel-coated balloon angioplasty (DCB group; n = 27) or standard PTA (PTA group; n = 23). Primary patency and clinical outcomes were assessed at 6, 12, and 24 months postoperatively. RESULTS:Over a 24-month period, the primary patency rate of the DCB group was significantly higher than that of the PTA group (P < 0.001), with Kaplan-Meier curves demonstrating sustained superiority at all time points (6 month: 100% vs. 55%; 12 month: 87.5% vs. 15%; and 24 month: 54.2% vs. 5%). The hazard ratio for primary patency between DCB and PTA was 8.35 (95% confidence interval: 3.72-18.74,P < 0.001). In addition, the DCB group demonstrated a significantly higher rate of freedom from clinically driven target lesion revascularization than the PTA group (88.0% vs. 31.8%; P < 0.001). The incidence of major adverse events did not significantly differ between groups. CONCLUSION:The use of paclitaxel-coated balloon catheters improved the angiographic and midterm clinical outcomes in most patients with in-stent restenosis.

BACKGROUND:Remimazolam is a novel, ultra-short-acting benzodiazepine. This systematic review and meta-analysis compared the anesthetic efficacy and safety of remimazolam versus propofol for procedural sedation and general anesthesia. METHOD:A comprehensive search of PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials was conducted through 26 July 2024. Randomized controlled trials comparing remimazolam and propofol for procedural sedation or general anesthesia were included. The primary outcome was the success rate of sedation or general anesthesia. Data were analyzed using fixed and random-effects models to calculate pooled risk ratios (RRs), mean differences, 95% confidence intervals (CIs), and P values. RESULTS:Twenty-seven studies involving 7283 patients met the inclusion criteria. Sedation and general anesthesia success rates were comparable between remimazolam and propofol (RR: 0.99; 95% CI: 0.97-1.00; P = 0.10; N = 4858). While remimazolam had a longer time to awake, it was associated with significantly lower rates of hypotension and injection pain. Rates of nausea, vomiting, and discharge times were similar between the drugs. Subgroup analyses revealed that during procedural sedation, remimazolam resulted in longer awakening times and a reduced risk of hypoxemia. However, these effects were not observed in general anesthesia. CONCLUSION:Remimazolam and propofol achieved comparable success rates for sedation and general anesthesia. Remimazolam reduced hypoxemia risk but prolonged awakening times during procedural sedation. It also lowered the incidence of hypotension and injection pain across both procedural sedation and general anesthesia. Additional studies are needed to further clarify its role, particularly in general anesthesia.

Delirium and postoperative cognitive dysfunction (POCD) are common complications post-cardiac surgery, yet no specific medical intervention is currently recommended for prevention. This study aimed to evaluate the efficacy of gastrodin infusion in preventing delirium and POCD in critically ill patients following cardiac surgery. A double-blind, randomized, placebo-controlled trial was conducted on patients aged 18–75, scheduled for coronary artery bypass grafting (CABG) surgery, with or without valve replacement. Participants were randomized in a 1:1 ratio to receive gastrodin infusion 600 mg twice daily or placebo from the day of surgery until the postoperative day (POD) 6. The co-primary outcomes were the incidences of delirium and POCD, assessed from ICU admission until POD 7 and at 1 and 3 months postoperatively. This study was registered with the Chinese Clinical Trials Registry (ChiCTR1800020414). Of 160 randomized participants, 155 were analyzed (77 gastrodin, 78 placebo) according to a modified intention to treat principle. The incidence of postoperative delirium was 19.5

Sepsis is a leading cause of in-hospital mortality, with more than 50% of patients developing Acute Lung Injury (ALI). Alveolar macrophages are the primary immune cells in lung tissue and play a crucial role in the pathogenesis of ALI. In this study, we investigated the potential therapeutic effects of dexmedetomidine (DEX) in both sepsis mice models of ALI and Lipopolysaccharide & Interferon gamma (LPS&IFN-γ)- stimulated macrophages, elucidating its underlying mechanism. In vivo experiments were conducted using the cecal ligation and puncture (CLP) technique to induce sepsis in mice, and intraperitoneal administration of DEX was initiated at 3, 6, 12 h post-CLP. Results showed that DEX significantly ameliorated CLP-induced lung tissue injury, impeded proinflammatory cytokine release, and reduced neutrophil infiltration. Additionally, DEX decreased M1 macrophage polarization in the lung tissue of septic mice. In vitro, experiments showed that DEX effectively attenuated the elevation of macrophage glycolysis levels induced by LPS & IFN-γ. Mechanistically, DEX treatment suppressed the phosphorylation of Pyruvate kinase M2 (PKM2) at the Y105 site and its nuclear translocation levels, thus disrupting the Warburg effect to reduce M1 cell polarization. Therefore, this work has demonstrated the role of DEX in macrophage polarization and sepsis-induced acute lung injury, providing valuable guidance for the treatment of critically ill patients with clinical sepsis.

The prevalence of type 2 diabetes mellitus (T2DM) is rising, with hypertension as a common comorbidity that significantly increases cardiovascular and microvascular risks. Accurate prediction of hypertension in T2DM is essential for early intervention and personalized management. In this editorial, we comment on a recent retrospective study by Zhao et al, which developed a nomogram model using a large cohort of 26850 patients to predict hypertension risk in patients with T2DM. The model incorporated key independent risk factors, including age, body mass index, duration of diabetes, low-density lipoprotein cholesterol and urine protein levels, demonstrating promising discriminative power and predictive accuracy in internal validation. However, its external applicability requires further confirmation. This editorial discusses the clinical value and limitations of the predictive model, highlighting the unfavorable impact of hypertension on T2DM patients. Future research should evaluate the potential contribution of other risk factors to enhance risk prediction and improve the management of T2DM comorbidities.

IntroductionNaringenin (Nar), a common flavanone abundant in citrus fruits and tomatoes, is common in diets. Although Nar can alleviate intestinal ischemia/reperfusion injury (IRI), the exact anti-inflammatory mechanisms are unclear and require further study.MethodsIn this study, we employed a comprehensive research strategy that integrated network pharmacology analysis with both in vitro and in vivo experimental validations to systematically elucidate Nar’s anti-inflammatory mechanisms in intestinal IRI.ResultsNetwork pharmacology uncovered 88 common anti-inflammatory targets for Nar in intestinal IRI. Among these, TNF, IL6, AKT1, IL1B, TP53, STAT3, and PTGS2 were identified as hub genes. Validation experiments demonstrated that Nar induced anti-inflammatory responses through downregulating calprotectin, IL-1β, IL-6, and TNF-α, while promoting IL-10 secretion. Additionally, Nar pretreatment significantly downregulated PTGS2 and phosphorylated STAT3 (p-STAT3). Further mechanistic investigations were conducted using the YAP inhibitor verteporfin (VP) in vitro and in vivo. Nar pretreatment activated YAP, thereby enhancing its anti-inflammatory effects. Conversely, inhibiting YAP activation with VP increased p-STAT3 and enhanced inflammatory responses, diminishing Nar’s efficacy.ConclusionThis study demonstrated that Nar inhibited intestinal inflammatory responses by activating YAP, which suppressed p-STAT3 expression, and provided a theoretical basis for Nar’s clinical application in intestinal IRI.