Integrin A5B1-mediated endocytosis of polystyrene nanoplastics: Implications for human lung disease and therapeutic targets.

The extensive use of plastic products has exacerbated micro/nanoplastic (MPs/NPs) pollution in the atmosphere, increasing the incidence of respiratory diseases and lung cancer. This study investigates the uptake and cytotoxicity mechanisms of polystyrene (PS) NPs in human lung epithelial cells. Transcriptional analysis revealed significant changes in cell adhesion pathways following PS-NPs exposure. Integrin α5ß1-mediated endocytosis was identified as a key promoter of PS-NPs entry into lung epithelial cells. Overexpression of integrin α5ß1 enhanced PS-NPs internalization, exacerbating mitochondrial Ca2+ dysfunction and depolarization, which induced reactive oxygen species (ROS) production. Mitochondrial dysfunction triggered by PS-NPs led to oxidative damage, inflammation, DNA damage, and necrosis, contributing to lung diseases. This study elucidates the molecular mechanism by which integrin α5ß1 facilitates PS-NPs internalization and enhances its cytotoxicity, offering new insights into potential therapeutic targets for microplastic-induced lung diseases.

Cluster headache: understandings of current knowledge and directions for whole process management.

Cluster headache (CH) is a common primary headache that severely impacts patients' quality of life, characterized by recurrent, severe, unilateral headaches often centered around the eyes, temples, or forehead. Distinguishing CH from other headache disorders is challenging, and its pathogenesis remains unclear. Notably, patients with CH often experience high levels of depression and suicidal tendencies, necessitating increased clinical attention. This comprehensive assessment combines various reports and the latest scientific literature to evaluate the current state of CH research. It covers epidemiology, population characteristics, predisposing factors, and treatment strategies. Additionally, we provide strategic insights into the holistic management of CH, which involves continuous, individualized care throughout the prevention, treatment, and rehabilitation stages. Recent advances in the field have revealed new insights into the pathophysiology of CH. While these findings are still evolving, they offer a more detailed understanding of the neurobiological mechanisms underlying this disorder. This growing body of knowledge, alongside ongoing research efforts, promises to lead to the development of more targeted and effective treatments in the future.

The diagnostic value of neutrophil to lymphocyte ratio, albumin to fibrinogen ratio, and lymphocyte to monocyte ratio in Parkinson's disease: a retrospective study.

Background: Parkinson's disease (PD) is a prevalent disorder of the central nervous system, marked by the degeneration of dopamine (DA) neurons in the ventral midbrain. In the pathogenesis of PD, inflammation hypothesis has been concerned. This study aims to investigate clinical indicators of peripheral inflammation in PD patients and to explore the diagnostic value of neutrophil-to-lymphocyte ratio (NLR), albumin-to-fibrinogen ratio (AFR), and lymphocyte-to-monocyte ratio (LMR) in assessing PD risk. Methods: This study included 186 patients with PD and 201 matched healthy controls (HC) with baseline data. Firstly, the differences of hematological indicators between PD group and healthy participants were compared and analyzed. Univariate and multivariate regression analyses were then conducted. Smooth curve fitting was applied to further validate the relationships between NLR, LMR, AFR, and PD. Subsequently, subgroup analysis was conducted in PD group according to different duration of disease and Hoehn and Yahr (H&Y) stage, comparing differences in clinical indicators. Finally, the receiver operating characteristic (ROC) curve was employed to assess the diagnostic value of NLR, LMR, and AFR in PD. Results: Compared to the HC group, the PD group showed significantly higher levels of hypertension, diabetes, neutrophil count, monocyte count, CRP, homocysteine, fibrinogen, and NLR. Conversely, levels of LMR, AFR, lymphocyte count, HDL, LDL, TG, TC, uric acid, and albumin were significantly lower. The multivariate regression model indicated that NLR (OR = 1.79, 95% CI: 1.39-2.31, p < 0.001), LMR (OR = 0.75, 95% CI: 0.66-0.85, p < 0.001), and AFR (OR = 0.79, 95% CI: 0.73-0.85, p < 0.001) were significant factors associated with PD. Smooth curve fitting revealed that NLR was positively linked to PD risk, whereas AFR and LMR were inversely associated with it. In ROC curve analysis, the AUC of AFR was 0.7290, the sensitivity was 63.98%, and the specificity was 76.00%. The AUC of NLR was 0.6200, the sensitivity was 50.54%, and the specificity was 71.50%. The AUC of LMR was 0.6253, the sensitivity was 48.39%, and the specificity was 73.00%. The AUC of the combination was 0.7498, the sensitivity was 74.19%, and the specificity was 64.00%. Conclusion: Our findings indicate that NLR, LMR, and AFR are significantly associated with Parkinson's disease and may serve as diagnostic markers.

Giant mucinous liposarcoma of the abdominal cavity: A case report.

RATIONALE: Mucinous liposarcoma myxoid liposarcoma is a malignant mucoid soft tissue tumor derived from undifferentiated stromal cells in perivascular, subbody cavity and intermuscular space, and composed of cells at different stages of differentiation from preadipocytes to mature cells. In rare cases, it may change from lipoma malignancy. The main manifestations is painless mass, relatively slow growth, the course can last decades, the prevalence of liposarcoma in the population is 14% to 18%, mainly in adults, male prevalence is higher than women, but not significant. The main good hair part is the thigh, have mucinous sex, high differentiation type, dedifferentiation type, polymorphic type. Clinical diagnosis is difficult, and there are no obvious symptoms in the early stage, so the diagnosis should be combined with B ultrasound, MRI, CT, and other auxiliary examinations. The gold standard is pathological examination. In December 2023, our department admitted a patient with a mucinous abdominal mass. The report is as follows. PATIENT CONCERNS: Does liposarcoma metastasize? Is any chemotherapy required after surgery? Will it ever relapse in the future? What is the survival period after surgery? DIAGNOSIS: Mucinous liposarcoma. INTERVENTIONS: Surgical resection of the sarcoma. RESULTS: The nodule sample was 33 * 28 * 13 cm, with complete capsule, gray and yellow sections, fine texture, soft, gray, red, grayish, and yellow mucoid nodules in some areas, and the maximum diameter of the nodules was 21cm. Immunohistochemistry was: CD34 (+), CDK 4 (+), CK (-), Desmin (weak +), Ki67 (index 5%), MDM 2 (-), p16 (weak +), S-100P (+), Vimentin (+), BCL-2 (+). He was also sent to the Department of Pathology of Peking Union Medical College Hospital for consultation with Professor Lu Zhaohui, whose consultation opinion was in line with myxoliposarcoma. CONCLUSION: Retroperitoneal liposarcoma is a common retroperitoneal tumor, but it is relatively rare in clinical practice; the overall morbidity is low, mainly manifested as abdominal pain and abdominal distension, abdominal distension, and a long course of disease; it is not sensitive to radiotherapy and chemotherapy, and should be closely follow up by CT examination to understand the recurrence and metastasis.

The Sources, Structures and Cytotoxicity of Animal-Derived Bisindole Compounds.

Bisindole compounds constitute a significant class of natural compounds distinguished by their characteristic bisindole structure and renowned for their anticancer properties. Over the past four decades, researchers have isolated 229 animal-derived bisindole compounds (ADBCs) from various animals. These compounds demonstrate a wide range of pharmacological properties, including cytotoxicity, antibacterial, antifungal, antiviral, and other activities. Notably, among these activities, cytotoxicity emerges as the most prominent characteristic of ADBCs. This review also summarizes the structureactivity relationship (SAR) studies associated with the cytotoxicity of these compounds and explores the druggability of these compounds. In summary, our objective is to provide an overview of the research progress concerning ADBCs, with the aim of fostering their continued development and utilization.

Association between vitamin B1 intake and hyperuricemia in adults.

Studies investigating the relationship between dietary vitamin B1 intake and risk of Hyperuricemia (HU) are scarce, the present study aimed to examine the association of dietary vitamin B1 intake and HU among adults. This cross-sectional study included 5750 adults whose data derived from National Health and Nutrition Examination Survey (NHANES) from March 2017 to March 2020. The dietary intake of vitamin B1 was assessed using 24-h dietary recall interviews. The characteristics of study participants were grouped into five levels according to the levels of vitamin B1 quintile. Multivariate logistic regression analysis was used to estimate the odds ratio (OR) and 95% confidence interval (CI) of HU, according to the vitamin B1 intake quintile for male and female separately. The dose-response relationship was determined by the restricted cubic spline (RCS). Smoothed curve fitting was used to assess serum uric acid concentration versus dietary vitamin B1 intake in the study population. The prevalence of hyperuricemia was 18.90% (20.15% and 17.79% for males and females, respectively) in the United States from March 2017 to March 2020. Multiple logistic regression analyses showed that in the male population, the HU ratio (OR) of vitamin B1 intake in Q2 to Q5 compared with the lowest quintile (Q1) was 0.75 (95% CI 0.52, 1.09), 0.70 (95% CI 0.48, 1.02), 0.66 (95% CI 0.44, 0.99) and 0.55 (95% CI 0.34, 0.90). The P for trend was 0.028. In women, the ORs for vitamin B1 intake Q2 to Q5 were 0.87 (95% CI 0.64, 1.19), 0.97 (0.68-1.38), 1.05 (0.69-1.60) and 0.75 (0.42-1.34), respectively. The P for trend was 0.876. The RCS curve revealed a linear relationship between vitamin B1 intake and the risk of hyperuricemia in men (P nonlinear = 0.401). Smoothed curve fitting demonstrated a negative association between vitamin B1 intake and serum uric acid concentration in men, whereas there was no significant association between dietary vitamin B1 intake and the risk of hyperuricemia in women. In the US adult population, dietary vitamin B1 intake was negatively associated with hyperuricemia in males.

U-Shaped Relationship Between Fibrinogen Level and 10-year Mortality in Patients With Acute Coronary Syndrome: Prospective Cohort Study.

This study demonstrated that fibrinogen is an independent risk factor for 10-year mortality in patients with acute coronary syndrome (ACS), with a U-shaped nonlinear relationship observed between the two. These findings underscore the importance of monitoring fibrinogen levels and the consideration of long-term anti-inflammatory treatment in the clinical management of patients with ACS.

Parallel CNN-Deep Learning Clinical-Imaging Signature for Assessing Pathologic Grade and Prognosis of Soft Tissue Sarcoma Patients.

BACKGROUND: Traditional biopsies pose risks and may not accurately reflect soft tissue sarcoma (STS) heterogeneity. MRI provides a noninvasive, comprehensive alternative. PURPOSE: To assess the diagnostic accuracy of histological grading and prognosis in STS patients when integrating clinical-imaging parameters with deep learning (DL) features from preoperative MR images. STUDY TYPE: Retrospective/prospective. POPULATION: 354 pathologically confirmed STS patients (226 low-grade, 128 high-grade) from three hospitals and the Cancer Imaging Archive (TCIA), divided into training (n = 185), external test (n = 125), and TCIA cohorts (n = 44). 12 patients (6 low-grade, 6 high-grade) were enrolled into prospective validation cohort. FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T/Unenhanced T1-weighted and fat-suppressed-T2-weighted. ASSESSMENT: DL features were extracted from MR images using a parallel ResNet-18 model to construct DL signature. Clinical-imaging characteristics included age, gender, tumor-node-metastasis stage and MRI semantic features (depth, number, heterogeneity at T1WI/FS-T2WI, necrosis, and peritumoral edema). Logistic regression analysis identified significant risk factors for the clinical model. A DL clinical-imaging signature (DLCS) was constructed by incorporating DL signature with risk factors, evaluated for risk stratification, and assessed for progression-free survival (PFS) in retrospective cohorts, with an average follow-up of 23 ± 22 months. STATISTICAL TESTS: Logistic regression, Cox regression, Kaplan-Meier curves, log-rank test, area under the receiver operating characteristic curve (AUC)，and decision curve analysis. A P-value <0.05 was considered significant. RESULTS: The AUC values for DLCS in the external test, TCIA, and prospective test cohorts (0.834, 0.838, 0.819) were superior to clinical model (0.662, 0.685, 0.694). Decision curve analysis showed that the DLCS model provided greater clinical net benefit over the DL and clinical models. Also, the DLCS model was able to risk-stratify patients and assess PFS. DATA CONCLUSION: The DLCS exhibited strong capabilities in histological grading and prognosis assessment for STS patients, and may have potential to aid in the formulation of personalized treatment plans. TECHNICAL EFFICACY: Stage 2.

A 38-Year-Old Woman With REM Predominant Central Sleep Apnea After Bulbar Infarction.

CASE PRESENTATION: A 38-year-old previously healthy woman was referred to our sleep center for recurrent witnessed breathing arrest during sleep. She had been brought to the ED 3 months earlier because of sudden onset of dizziness with nausea and vomiting, numbness and weakness of the left limb, less clear speech, double vision, dysphagia, and choking cough while drinking water. Brain MRI showed an acute cerebral infarction in the left medulla oblongata (Fig 1). High-resolution MRI showed vertebral artery dissection (Fig 2). Antiplatelet aggregation, lipid reduction, plaque stabilization, and trophic nerve treatments were administered, and the left limb strength, speech, and swallowing function improved. She complained of poor sleep and difficulties with memory.

Synthesis of Asp-based lactam cyclic peptides using an amide-bonded diaminodiacid to prevent aspartimide formation.

Asp-based lactam cyclic peptides are considered promising drug candidates. However, using Fmoc solid-phase peptide synthesis (Fmoc-SPPS) for these peptides also causes aspartimide formation, resulting in low yields or even failure to obtain the target peptides. Here, we developed a diaminodiacid containing an amide bond as a ß-carboxyl-protecting group for Asp to avoid aspartimide formation. The practicality of this diaminodiacid has been illustrated by the synthesis of lactam cyclic peptide cyclo[Lys9,Asp13] KIIIA7-14 and 1Y.

A cell-permeable Ub-Dha probe for profiling E1-E2-E3 enzymes in live cells.

Activity-based ubiquitin probes (Ub-ABPs) have recently been developed as effective tools for studying the capabilities of E1-E2-E3 enzymes, but most of them can only be used in cell lysates. Here, we report the first cell-penetrating Ub-Dha probes based on thiazolidine-protected cysteines, which enable successful delivery into cells confirmed by a fluorophore at the N-terminus of Ub and live-cell fluorescence microscopy. A total of 18 E1-E2-E3 enzymes in live cells were labelled and enriched in combination with label-free quantification (LFQ) mass spectrometry. This work provided a new cell-penetrating Ub tool for studying the activity and function of Ub-related enzymes.

Highly Enantioselective Catalysis by Enzyme Encapsulated in Metal Azolate Frameworks with Micelle-Controlled Pore Sizes.

Encapsulating enzymes within metal-organic frameworks has enhanced their structural stability and interface tunability for catalysis. However, the small apertures of the frameworks restrict their effectiveness to small organic molecules. Herein, we present a green strategy directed by visible linker micelles for the aqueous synthesis of MAF-6 that enables enzymes for the catalytic asymmetric synthesis of chiral molecules. Due to the large pore aperture (7.6 Å), double the aperture size of benchmark ZIF-8 (3.4 Å), MAF-6 allows encapsulated enzyme BCL to access larger substrates and do so faster. Through the optimization of surfactants' effect during synthesis, BCL@MAF-6-SDS (SDS = sodium dodecyl sulfate) displayed a catalytic efficiency (Kcat/Km) that was 420 times greater than that of BCL@ZIF-8. This biocomposite efficiently catalyzed the synthesis of drug precursor molecules with 94-99% enantioselectivity and nearly quantitative yields. These findings represent a deeper understanding of de novo synthetic encapsulation of enzyme in MOFs, thereby unfolding the great potential of enzyme@MAF catalysts for asymmetric synthesis of organics and pharmaceuticals.

Targeting Protein Phosphatases for the Treatment of Chronic Liver Disease.

There exists a huge number of patients suffering from chronic liver disease worldwide. As a disease with high incidence and mortality worldwide, strengthening the research on the pathogenesis of chronic liver disease and the development of novel drugs is an important issue related to the health of all human beings. Phosphorylation modification of proteins plays a crucial role in cellular signal transduction, and phosphatases are involved in the development of liver diseases. Therefore, this article summarized the important role of protein phosphatases in chronic liver disease with the aim of facilitating the development of drugs targeting protein phosphatases for the treatment of chronic liver disease.

The management of non-culprit vessel(s) in patients with unstable angina/non-ST elevation myocardial infarction and chronic kidney dysfunction.

BACKGROUND AND AIMS: The clinical effects of multivessel interventions in patients with unstable angina/non-ST-segment elevation myocardial infarction (UA/NSTEMI), multivessel disease (MVD) and chronic kidney disease (CKD) remain uncertain. This study aimed to investigate the safety and effectiveness of intervention in non-culprit lession(s) among this cohort. METHODS: We consecutively included patients diagnosed with UA/NSTEMI, MVD and CKD between January 2008 and December 2018 at our centre. After successful percutaneous coronary intervention (PCI), we compared 48-month overall mortality between those undergoing multivessel PCI (MV-PCI) through a single-procedure or staged-procedure approach and culprit vessel-only PCI (CV-PCI) after 1:1 propensity score matching. We conducted stratified analyses and tests for interaction to investigate the modifying effects of critical covariates. Additionally, we recorded the incidence of contrast-induced nephropathy (CIN) to assess the perioperative safety of the two treatment strategies. RESULTS: Of the 749 eligible patients, 271 pairs were successfully matched. Those undergoing MV-PCI had reduced all-cause mortality (hazard ratio (HR): 0.67, 95% confidence interval (CI): 0.48-0.67). Subgroup analysis showed that those with advanced CKD (estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m2 ) could not benefit from MV-PCI (P = 0.250), and the survival advantage also tended to diminish in diabetes (P interaction < 0.01; HR = 0.95, 95% CI = 0.65-1.45). Although the staged-procedure approach (N = 157) failed to bring additional survival benefits compared to single-procedure MV-PCI (N = 290) (P = 0.460), it showed a tendency to decrease the death risk. CIN risks in MV-PCI and CV-PCI groups were not significantly different (risk ratio = 1.60, 95% CI = 0.94-2.73). CONCLUSION: Among patients with UA/NSTEMI and non-diabetic CKD and an eGFR > 30 mL/min/1.73 m2 , MV-PCI was associated with a reduced risk of long-term death but did not increase the incidence of CIN during the management of MVD compared to CV-PCI. And staged procedures might be a preferable option over single-procedure MV-PCI.

STELLATE GANGLION BLOCK REVERSES PHSML-INDUCED VASCULAR HYPOREACTIVITY THROUGH INHIBITING AUTOPHAGY-MEDIATED PHENOTYPIC TRANSFORMATION OF VSMCs.

ABSTRACT: Posthemorrhagic shock mesenteric lymph (PHSML) return-contributed excessive autophagy of vascular smooth muscle cells (VSMCs) is involved in vascular hyporeactivity, which is inhibited by stellate ganglion block (SGB) treatment. The contractile phenotype of VSMCs transforms into a synthetic phenotype after stimulation with excessive autophagy. Therefore, we hypothesized that SGB ameliorates PHSML-induced vascular hyporeactivity by inhibiting autophagy-mediated phenotypic transformation of VSMCs. To substantiate this hypothesis, a hemorrhagic shock model in conscious rats was used to observe the effects of SGB intervention or intravenous infusion of the autophagy inhibitor 3-methyladenine (3-MA) on intestinal blood flow and the expression of autophagy- and phenotype-defining proteins in mesenteric secondary artery tissues. We also investigated the effects of intraperitoneal administration of PHSML intravenous infusion and the autophagy agonist rapamycin (RAPA) on the beneficial effect of SGB. The results showed that hemorrhagic shock decreased intestinal blood flow and enhanced the expression of LC3 II/I, Beclin 1, and matrix metalloproteinase 2, which were reversed by SGB or 3-MA treatment. In contrast, RAPA and PHSML administration abolished the beneficial effects of SGB. Furthermore, the effects of PHSML or PHSML obtained from rats treated with SGB (PHSML-SGB) on cellular contractility, autophagy, and VSMC phenotype were explored. Meanwhile, the effects of 3-MA on PHSML and RAPA on PHSML-SGB were observed. The results showed that PHSML, but not PHSML-SGB, incubation decreased VSMC contractility and induced autophagy activation and phenotype transformation. Importantly, 3-MA administration reversed the adverse effects of PHSML, and RAPA treatment attenuated the effects of PHSML-SGB incubation on VSMCs. Taken together, the protective effect of SGB on vascular reactivity is achieved by inhibiting excessive autophagy-mediated phenotypic transformation of VSMCs to maintain their contractile phenotype.

Superantigen-fused T cell engagers for tumor antigen-mediated robust T cell activation and tumor cell killing.

Inadequate T cell activation has severely limited the success of T cell engager (TCE) therapy, especially in solid tumors. Enhancing T cell activity while maintaining the tumor specificity of TCEs is the key to improving their clinical efficacy. However, currently, there needs to be more effective strategies in clinical practice. Here, we design novel superantigen-fused TCEs that display robust tumor antigen-mediated T cell activation effects. These innovative drugs are not only armed with the powerful T cell activation ability of superantigens but also retain the dependence of TCEs on tumor antigens, realizing the ingenious combination of the advantages of two existing drugs. Superantigen-fused TCEs have been preliminarily proven to have good (>30-fold more potent) and specific (>25-fold more potent) antitumor activity in vitro and in vivo. Surprisingly, they can also induce the activation of T cell chemotaxis signals, which may promote T cell infiltration and further provide an additional guarantee for improving TCE efficacy in solid tumors. Overall, this proof-of-concept provides a potential strategy for improving the clinical efficacy of TCEs.

Ent-labdane-type diterpene glycosides obtained from Rubus chingii Hu and their inhibitory effects on PDE5A activity.

In this study, 16 new ent-labdane-type diterpene glycosides, designated as goshonosides J1-J16 (1-16), along with nine previously known diterpene glycosides (17-25) were extracted from the fruits of Rubus chingii Hu. The structures of goshonosides J1-J16 were elucidated using various analytical techniques, such as nuclear magnetic resonance, electron capture detector ECD, high-resolution electrospray ionization mass spectrometry HREIMS, single-crystal X-ray diffraction, and hydrolysis. Furthermore, the isolates' efficacy in inhibiting the activity of phosphodiesterase type 5 A was evaluated. Goshonosides J1, J2, and G effectively inhibited the activity of the aforementioned enzyme (IC50 values: 6.15 ± 1.76, 3.27 ± 0.65, and 9.61 ± 2.36 µM, respectively). Our findings highlight the remarkable structural diversity of bioactive compounds in R. chingii Hu and offer insights into the use of this shrub.

Design, synthesis and triglyceride-lowering activity of tricyclic matrine derivatives for the intervention of non-alcoholic fatty liver disease.

Thirty new tricyclicmatrinic derivatives were successively synthesized and evaluated for their inhibitory activity on the accumulation of triglycerides (TG) in AML12 cells, using 12 N-m-trifluoromethylbenzenesulfonyl matrine (1) as the hit compound. Among the analogues, compound 7n possessing 11-trimethylbutylamine quaternary exerted the highest in vitro TG-lowering potency, as well as a good safety profile. 7n significantly attenuated the hepatic injury and steatosis, and ameliorated dyslipidemia and dysglycemia in the mice with non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet. Primary mechanism study revealed that upregulation of peroxisome proliferator-activated receptors α (PPARα)-carnitine palmitoyltransferase 1A (CPT1A) pathway mediated the efficacy of 7n. Our study provides powerful information for developing this kind of compound into a new class of anti-NAFLD candidates, and compound 7n is worthy of further investigation as an ideal lead compound.

Optimal treatment of asymptomatic patients with severe aortic stenosis: protocol of a prospective, multicentre, registry study.

INTRODUCTION: Decisions regarding the optimal timing of intervention for asymptomatic aortic stenosis (AS) are controversial. The study aims to identify potential risk factors for asymptomatic patients with severe AS that are associated with worse prognosis and to evaluate the benefits of early interventions for asymptomatic patients presenting with one or more additional risk factors. METHODS AND ANALYSIS: This is a non-interventional, prospective, open-label, multicentre registry study across China. A total of 1000 patients will be enrolled and categorised as symptomatic or asymptomatic. The primary endpoint is the occurrence of all-cause mortality, stroke, acute myocardial infarction and heart failure-related hospitalisation at 1-year follow-up. In asymptomatic severe AS patients presenting with one or more risk factors, the occurrence rate of the primary endpoint between those who undergo transcatheter aortic valve replacement (TAVR) and those who do not will be compared. We will also compare the occurrence rate of the primary endpoint for asymptomatic severe AS patients with additional risk factors who undergo TAVR with those presenting with symptoms. This study is believed to provide additional evidence to help clinicians identify and refer severe AS patients who are asymptomatic but present with additional risk factors for early intervention of TAVR. ETHICS AND DISSEMINATION: The study protocol has been approved by the local ethics committee of each participating site: West China Hospital, Sichuan University; Sir Run Run Shaw Hospital, Zhejiang University School of Medicine; Second Hospital of Hebei Medical University; Tianjin Chest Hospital; and First Affiliated Hospital of Nanchang University. All participants will provide written informed consent. Study results will be published through academic conferences and peer-reviewed journals. TRIAL REGISTRATION: This study was registered at the Chinese Clinical Trial Registry (https:// www.chictr.org.cn), with the registration number ChiCTR2200064853.