Background and aims: Randomized trials have demonstrated the benefit of endovascular treatment (EVT) in moderate-to-severe acute basilar artery occlusion (BAO), but its benefit in acute mild BAO remains uncertain. This multicenter, retrospective study aimed to explore the EVT efficacy in acute BAO with a low National Institutes of Health Stroke Scale (NIHSS). Methods: Patients with acute BAO and NIHSS<10, hospitalized at 5 stroke centers in China between January 2020 and December 2023, were included and divided into EVT and standard medical treatment (SMT) groups. The primary outcome was 90-day functional independence defined as a modified Rankin Scale (mRS) of 0-2. Secondary outcomes include proportions of 90-day mRS 0-1 and 0-3. Symptomatic intracerebral hemorrhage (sICH) within 48 hours and 90-day mortality were assessed as safety outcomes. Results: 315 BAO patients with NIHSS <10 were enrolled (229 [72.7%] male; median [IQR] age, 65 [58-72] years; median [IQR] baseline NIHSS, 6 [3-8] points), 161 (51.1%) of whom underwent EVT and 154 (48.9%) received SMT only. The EVT group had a higher rate of 90-day functional independence (68.9% vs. 44.8%, adjusted OR, 3.69 [95% CI, 2.04-6.68]; P <.001). There was no significant difference in 90-day mortality (4.3% vs. 4.5%, adjusted OR, 1.22 [95% CI, 0.37-4.03]; P =.80), however, EVT was associated with a higher risk of sICH (8.2% vs. 3.9%, adjusted OR, 3.86 [95% CI, 1.18-12.61]; P =.03). Conclusions: In this cohort of patients with acute mild BAO, EVT was associated with an improved 90-day functional outcome compared with SMT alone, although increasing the risk of sICH.
Background: The effect of rescue balloon angioplasty or stenting for acute large vessel occlusion (LVO) stroke with residual intracranial atherosclerotic stenosis (ICAS) following endovascular thrombectomy (EVT) remains uncertain. This multicenter retrospective study aimed to investigate whether rescue balloon angioplasty or stenting is beneficial in improving neurological recovery in LVO patients with residual ICAS following EVT. Methods: We retrospectively included patients with LVO who underwent EVT with residual ICAS >50% between January 1, 2020, and December 31, 2024 from six stroke centers in China. Eligible patients were divided into two groups: those who received rescue balloon angioplasty with or without stenting (rescue group) and those who received thrombectomy alone (control group). The primary outcome was functional independence at 90 days, defined by a score on the modified Rankin Scale (mRS) of 0 to 2. Safety outcomes included symptomatic intracranial hemorrhage, any intracranial hemorrhage, and 90-day mortality. Results: 292 patients were included in the study, with 186 patients in the rescue group and 106 in the control group. No statistically significant differences were observed between the rescue and control groups regarding the primary outcome (54.8% vs. 63.6%; adjusted OR: 0.92, 95% CI: 0.44–1.91; P=0.82). In safety outcomes, the proportion of any intracranial hemorrhage was numerically higher in the rescue group compared to the control group, although the difference was statistically non-significant after adjustment for confounding factors (19.7% vs. 5.5%; adjusted OR: 1.90, 95 CI%: 0.64-6.46; P=0.27). The 90-day mortality (6.4% vs. 3.6%; adjusted OR:1.21, 95CI%: 0.20-9.91; P=0.85) and symptomatic intracranial hemorrhage (3.2% vs. 1.8%; adjusted OR: 1.42, 95 CI%: 0.19-16.90; P=0.75) also showed no significant differences. Conclusion: Rescue balloon angioplasty and stenting should be applied with greater caution in patients with residual ICAS following LVO thrombectomy.
Background: Acute ischemic stroke (AIS) caused by severe intracranial atherosclerotic stenosis (ICAS) presents with significant hemodynamic compromise and poor functional outcome. It remains unclear whether immediate angioplasty or stenting could improve functional outcome in AIS patients with severe ICAS who present within 24 hours of symptom onset and are not indicated for mechanical thrombectomy. Method: AIS patients with symptom onset within 24 hours and imaging-confirmed severe ICAS (70%-99%) in the culprit vessel, admitted to 7 stroke centers in China between January 2020 and December 2024, were included and divided into the immediate endovascular treatment (EVT) group with angioplasty or stenting, and the standard medical treatment (SMT) group. The primary outcome was the distribution of modified Rankin Scale (mRS) scores at 90 days. Symptomatic intracranial hemorrhage (sICH) within 24 hours and mortality within 90 days were assessed as safety outcomes. Multivariable models were used to estimate the effectiveness of immediate EVT. Results: A total of 242 patients were included, with a mean age of 65.7 years (SD, 12.3) and a median baseline NIHSS score of 5 (IQR, 2-8). 96 (39.7%) of the patients underwent immediate EVT, and 146 (60.3%) received SMT. The median 90-day mRS score was 1 (IQR, 0-3) in the immediate EVT group and 1 (IQR, 1-3) in the SMT group. The immediate EVT group showed a shift towards better functional outcomes on the mRS (adjusted common odds ratio 2.73 [95% CI, 1.50 to 4.99]; P = 0.001). There was no significant difference in sICH within 24 hours (1.0% vs. 1.4%; adjusted RR, 0.36 [95% CI, 0.02-5.35]; P = 0.456) and mortality within 90 days (2.1% vs. 1.4%; adjusted HR, 1.01 [95% CI, 0.92-1.11]; P = 0.934). Conclusions: In patients with AIS due to severe ICAS, immediate EVT was associated with an improved 90-day functional outcome compared with SMT alone, but not with an increased risk of sICH or mortality. Further prospective, multicenter, randomized trials are warranted to validate the efficacy of immediate EVT for AIS patients due to severe ICAS.
Alzheimer's disease (AD) is the most common neurodegenerative disease leading to dementia in the elderly, and the mechanisms of AD have not been fully defined. Circular RNAs (circRNAs), covalently closed RNAs produced by reverse splicing, have critical effects in the pathogenesis of AD. CircRNAs participate in production and clearance of Aβ and tau, regulate neuroinflammation, synaptic plasticity and the process of apoptosis and autophagy, indicating that circRNAs may be alternative biomarkers and therapeutic targets. Our review summarizes the functions of circRNAs in the progression and development of AD, which provide insights into the prospect of circRNAs in the diagnosis and treatment of AD.
Atmospheric formaldehyde (HCHO) is a major component of oxygenated volatile organic compounds (OVOCs) and plays an important role in O3 formation and atmospheric oxidation capacity. In this study, seasonal observations of gaseous pollutants (HCHO, O3, peroxyacetyl nitrate (PAN), CO, NOx, and VOCs) and ambient conditions (JHCHO, JNO2, solar radiation, temperature, relative humidity, wind speed, and wind direction) were conducted in a coastal city in southeast China. The average HCHO concentrations were 2.54 ppbv, 3.38 ppbv, 2.53 ppbv, and 1.98 ppbv in spring, summer, autumn, and winter, respectively. Diurnal variations were high in the daytime and low in the nighttime, and the peak times varied in different seasons. The correlation between HCHO and O3 was not significant in spring and winter, which is likely related to the effects of photochemical reactions and diffusion conditions. The contributions of background (23.0%), primary (47.6%), and secondary (29.4%) sources to HCHO were quantified using multiple linear regression (MLR) models, revealing that secondary formation was the most significant contributor in summer, whereas primary emissions were predominant in spring. These findings help to improve the understanding of the influence of atmospheric formaldehyde on photochemical pollution control in coastal cities.
This study investigated SOX18's role in calcific aortic valve disease (CAVD). Aortic valve specimens from 67 patients undergoing valve replacement were stratified into control (n = 18), mild (n = 20), and severe calcification (n = 29) groups based on Alizarin Red staining. Immunohistochemistry revealed SOX18 expression localized to valve interstitial cells (VICs), with significantly higher levels in calcified versus control valves (P < .001). Elevated SOX18 was particularly associated with the inflammatory factors CD68 and Nuclear Factor-kappa B (NF-κB) p65, suggesting a potential link between SOX18, inflammation and CAVD progression. These findings highlight SOX18 as a possible mediator in valvular calcification.
BACKGROUND:Randomized trials have demonstrated the benefit of endovascular treatment (EVT) in moderate-to-severe acute basilar artery occlusion (BAO), but its benefit in acute mild BAO remains uncertain. This multicenter, retrospective cohort study aimed to explore the efficacy of EVT in acute BAO with a low National Institutes of Health Stroke Scale. METHODS:Patients with acute BAO and National Institutes of Health Stroke Scale <10, hospitalized at 5 stroke centers in China between January 2020 and December 2023, were included and divided into EVT and standard medical treatment groups. The primary outcome was 90-day functional independence, defined as a modified Rankin Scale score of 0 to 2. Secondary outcomes include proportions of 90-day modified Rankin Scale score of 0 to 1 and 0 to 3. Symptomatic intracerebral hemorrhage within 48 hours and 90-day mortality were assessed as safety outcomes. RESULTS:Three hundred fifteen patients with BAO with National Institutes of Health Stroke Scale <10 were enrolled (229 [72.7%] male; median [interquartile range] age, 65 [58-72] years; median [interquartile range] baseline National Institutes of Health Stroke Scale score, 6 [3-8] points), 161 (51.1%) of whom underwent EVT and 154 (48.9%) received standard medical treatment. The EVT group had a higher rate of 90-day functional independence (68.9% versus 44.8%; adjusted odds ratio, 3.69 [95% CI, 2.04-6.68]; P<0.001). There was no significant difference in 90-day mortality (4.3% versus 4.5%; adjusted odds ratio, 1.22 [95% CI, 0.37-4.03]; P=0.80). However, EVT was associated with a higher risk of symptomatic intracerebral hemorrhage (8.2% versus 3.9%; adjusted odds ratio, 3.86 [95% CI, 1.18-12.61]; P=0.03). CONCLUSIONS:In this cohort of patients with acute mild BAO, EVT was associated with an improved 90-day functional outcome compared with standard medical treatment alone, although the risk of symptomatic intracerebral hemorrhage was increased.
The role of macrophages (M Phi s) remains incompletely understood in kidney injury and repair. The plasticity of M Phi s offers an opportunity to polarize them toward mediating injury resolution in both native and transplanted kidneys undergoing ischemia and/or rejection. Here, we show that infiltrating kidney M Phi s augmented their own allograft inflammatory factor 1 (AIF-1) expression after injury. Aif1 genetic deletion led to M Phi polarization toward a reparative phenotype while halting the development of kidney fibrosis. The enhanced repair was mediated by higher levels of antiinflammatory and proregenerative markers, leading to a reduction in cell death and an increase in proliferation of kidney tubular epithelial cells after ischemia followed by reperfusion injury (I/RI). Adoptive transfer of Aif1-/- M Phi s into Aif1+/+ mice conferred protection against I/RI. Conversely, depletion of M Phi s reversed the tissue-reparative effects in Aif1-/- mice. We further demonstrated increased expression of AIF-1 in human kidney biopsies from native kidneys with acute kidney injury or chronic kidney disease, as well as in biopsies from kidney allografts undergoing acute or chronic rejection. We conclude that AIF-1 is a M Phi marker of renal inflammation, and its targeting uncouples M Phi reparative functions from profibrotic functions. Thus, therapies inhibiting AIF-1 when ischemic injury is inevitable have the potential to reduce the global burden of kidney disease.
The support effect of sulfated SnO2, TiO2, ZrO2, and SiO2 on FeVO4/CeO2-nanosheet was systematically investigated in this work. Among them, FeVO4/CeO2-nanosheet/sulfated-SnO2 (FeVCe/SSn) catalyst exhibited the widest operating temperature window (227-422 degrees C) with efficient NOx conversion beyond 90 % and N-2 selectivity exceeding 97 %, as well as superior resistance to SO2 and H2O (above 90 % activity retention for 24 h). The catalytic performance followed the order: FeVCe/SSn > FeVCe/STi > FeVCe/SZr > FeVCe/SSi, which aligns well with their redox properties. FeVCe/SSn presents the best redox ability and the second highest surface acidity. Owing to the most pronounced interaction of sulfated SnO2 with FeVO4 and CeO2 nanosheet, surface oxygen vacancies were significantly increased; simultaneously, sulfated SnO2 provided abundant superacidic Br & oslash;nsted acid sites and Lewis acid sites inherent to SnO2. This synergistic effect enhanced NH3 adsorption/activation and suppressed SO2 adsorption, thereby improving SCR activity and SO2/H2O resistance. The plausible mechanistic studies reveal that the SCR reaction over FeVCe/SSn is governed by a synergistic Eley-Rideal and Langmuir-Hinshelwood pathway. This study demonstrates that the rational design of acid-site density and the interfacial synergy between support and active phase constitute a feasible design principle for SCR catalysts that simultaneously afford a broad temperature window and high SO2/H2O durability.
Lactate plays diverse roles in brain pathophysiology, including ischemic stroke. Here, the role of lysine lactylation, an epigenetic modification of lactate, in cerebral ischemia is investigated. Using a mouse model of transient middle cerebral artery occlusion, increased brain lactate levels and global protein lactylation are observed. Proteomics analysis reveals significant lactylation of non-histone proteins in the ischemic penumbra. Lactylation of MeCP2, a transcriptional regulator, is identified as a protective mechanism against stroke-induced neuronal death. Inhibition of MeCP2 lactylation through chemical or genetic manipulation increases infarct volume and aggravates neurological deficits. Mechanistically, MeCP2 lactylation at K210/K249 represses the transcription of apoptosis-associated genes, including Pdcd4 and Pla2g6, thereby attenuating neuronal apoptosis. Additionally, HDAC3 and p300 are identified as key enzymes that regulate MeCP2 lactylation post-stroke. The findings suggest that MeCP2 lactylation offers a potential therapeutic target for alleviating neuronal damage and improving stroke outcomes.
Developing eco-friendly catalysts with high NOx removal efficiency and SO2 resistance in a wide temperature range is crucial. A series of efficient CeVO4/sulfated-SnO2 (CeV/Sn-S) and CeVO4/SnO2 (CeV/SnO2) catalysts were developed, and the optimal mass fraction of CeVO4 was 9 wt%. 9%CeV/SnO2 and 9%CeV/Sn-S achieved over 90.0 % NOx conversion at 220-385 and 240-430 degrees C, respectively, and they both showed notable SO2 resistance. CeV, 9%CeV/SnO2 and 9%CeV/Sn-S displayed different acid sites and SO2 adsorption capabilities. CeV exhibited low surface acidity, primarily Br & Oslash;nsted acidity. The introduction of SnO2 enhanced Lewis acidity, while sulfated SnO2 addition increased both Lewis and Br & Oslash;nsted acidity, and reduced SO2 adsorption, which benefitedthe SO2 resistance. 9%CeV/Sn-S had more lattice defects, a lager surface area, and higher Ce4+ and V5+ ratios than 9%CeV/SnO2, indicating a stronger interaction between CeVO4 and sulfated SnO2. Then, 9%CeV/SnS catalyst's strong NH3 adsorption and moderate redox properties contributed to its higher NOx conversions and N2 selectivity above 330 degrees C, along with a broader operational window. Both Eley-Rideal (E-R) and LangmuirHinshelwood (L-H) mechanisms were observed in these catalysts. However, the presence of sulfates on 9% CeV/Sn-S limited NOx adsorption, thereby reducing the contribution of L-H mechanism. The 9%CeV/SnO2 catalyst's strong Lewis acidity and abundant adsorbed NOx species favored the L-H mechanism, resulting in its higher NOx conversion below 250 degrees C compared to 9%CeV/Sn-S. This work contributes to sharpening comprehension for the influence of acid sites and steering the design of novel SCR catalysts for efficient NOx abatement in practical applications.
Atmospheric PM2.5 samples were collected from Nan Kang City, Jiangxi Province, in four seasons from October 2018 to July 2019 to explore the pollution characteristics, sources, and health risks of heavy metals. The contents of 11 heavy metals (Cu, Fe, Zn, Mn, Cd, Co, As, Ba, Pb, Cr, and Ti) were determined using inductively coupled plasma mass spectrometry (ICP-MS), and the pollution characteristics of Cu, Fe, Zn, Mn, Cd, Co, As, Ba, and Pb were analyzed. Combined with enrichment factor analysis, multivariate analysis (maximum variance rotation factor analysis), absolute principal component linear regression (APCS-MLR), and positive definite matrix factor (PMF) models, the sources of heavy metals in atmospheric PM2.5 were quantitatively analyzed, and the human health risks of these elements were evaluated. The results showed that the average mass concentration of PM2.5 in the study area during the sampling period was 46.98 μg·m-3, which exceeded the national ambient air quality secondary standard, with the highest concentration observed in winter. The concentrations of the nine heavy metals were ranked as follows: Fe > Zn > Pb > As > Mn > Cu > Ba > Cd > Co. The results of enrichment factor analysis showed that the content of most metal elements in atmospheric PM2.5 in the study area exceeded the environmental background value of soil in Layer A of Jiangxi Province. Except Fe and Ba, the other heavy metals were relatively enriched in the environment and were greatly affected by human activities. Factor analysis showed that the heavy metal pollution sources of atmospheric PM2.5 in the study area mainly fell into four categories: motor vehicle sources, industrial sources, coal burning sources, and natural sources; Mn, Cu, and Zn were mainly from motor vehicle sources; Co was mainly from industrial sources represented by the furniture factory; As, Cd, and Pb were mainly from coal burning; and Fe and Ba were mainly from natural sources. APCS-MLR and PMF model analysis showed that the pollution sources caused by human activities (motor vehicle sources, industrial sources, and coal sources) had a higher contribution rate, and the contribution rate of coal sources in the two models ranged from 20-40%. Health risk assessment analysis showed that Cu, Pb, Zn, Mn, Cd, Co, and As did not have non-carcinogenic risks, and the non-carcinogenic risks were in the order of children > adult men > adult women. As and Mn had potential carcinogenic risks for all three groups, and the carcinogenic risk for adult men was the highest.
Importance:Functional outcomes in patients with acute ischemic stroke due to large-vessel occlusion who undergo thrombectomy remain suboptimal, and the benefits of intra-arterial alteplase after thrombectomy remain uncertain. Objective:To investigate whether treatment with intra-arterial alteplase after successful endovascular reperfusion improves functional outcomes among patients with acute, anterior-circulation, large-vessel occlusion stroke. Design, Setting, and Participants:This multicenter, randomized clinical trial recruited patients with anterior-circulation, large-vessel occlusion stroke within 24 hours of symptom onset who achieved successful reperfusion (expanded Thrombolysis in Cerebral Infarction scale score of ≥2b50) after thrombectomy. Guideline-based intravenous thrombolysis was allowed. Patients were randomized between August 1, 2023, and October 16, 2024, and the trial was conducted at 28 hospitals in China. Final follow-up occurred on January 7, 2025. Interventions:Intra-arterial alteplase treatment (n = 164) with 0.225 mg/kg (maximum dose of 20 mg) vs standard treatment (n = 160). Main Outcomes and Measures:The primary outcome was the proportion of patients with a modified Rankin Scale score of 0 or 1 at 90 days (score range, 0 [no symptoms] to 6 [death]; a score of 0 or 1 indicates an excellent outcome). The safety outcomes included symptomatic intracranial hemorrhage within 36 hours of randomization, all-cause mortality within 90 days, and any intracranial hemorrhage within 36 hours. Results:Of the 324 patients randomized (median age, 68 years [IQR, 58-75 years]; 99 were female [30.6%]), 1 patient in each group was lost to follow-up. The proportion of patients with a modified Rankin Scale score of 0 or 1 at 90 days was 44.8% (73/163) in the intra-arterial alteplase group vs 30.2% (48/159) in the standard treatment group (adjusted risk ratio [RR], 1.45 [95% CI, 1.08-1.96]; P = .01). The proportion of patients with symptomatic intracranial hemorrhage within 36 hours was 4.3% (7/164) in the intra-arterial alteplase group vs 5.0% (8/160) in the standard treatment group (adjusted RR, 0.85 [95% CI, 0.43-1.69]; P = .67). The proportion of patients with all-cause mortality within 90 days was 17.1% (28/164) in the intra-arterial alteplase group vs 11.3% (18/160) in the standard treatment group (adjusted hazard ratio, 1.60 [95% CI, 0.88-2.89]; P = .12). The proportion of patients with any intracranial hemorrhage within 36 hours was 32.9% (54/164) in the intra-arterial alteplase group vs 26.9% (43/160) in the standard treatment group (adjusted RR, 1.22 [95% CI, 0.92-1.63]; P = .17). Conclusions and Relevance:Among patients with acute, anterior-circulation, large-vessel occlusion stroke who achieved successful endovascular reperfusion by mechanical thrombectomy, intra-arterial alteplase resulted in a higher likelihood of excellent outcomes at 90 days. The incidence of all-cause mortality and any intracranial hemorrhage was higher in patients who received intra-arterial alteplase, although these differences were not statistically significant. Trial Registration:ClinicalTrials.gov Identifier: NCT05856851.
Dendritic cells (DCs) are implicated in the progression of chronic kidney disease (CKD), and emerging evidence demonstrates that metabolic reprogramming profoundly influences DC differentiation and activation. Dynamin-related protein 1 (Drp1), a central regulator of mitochondrial fission, modulates mitochondrial metabolism; however, its role in DC-mediated immune responses remains unclear. To investigate the role of myeloid Drp1 in regulating DC function and CKD, we generate CD11c-specific Drp1 knockout mice (Drp1 MKO) by breeding Drp1 flox/flox with Cd11c-Cre mice. Drp1 expression was significantly reduced in splenic DCs (0.45 ± 0.01 vs. 1.0 ± 0.09 au; p <0.001) and BMDCs (0.20 ± 0.003 vs. 1.0 ± 0.009 au; p <0.001) from Drp1 MKO compared to wild-type (WT) mice. At baseline, Drp1 MKO mice had normal kidneys and similar renal immune cell profiles compared WT mice. However, following nephrotoxic serum (NTS)-induced CKD, Drp1 MKO mice showed higher mortality (50% vs. 10%; p =0.057), elevated BUN levels (178 ± 23 vs. 91 ± 14 mg/dL; p<0.05), and more severe kidney injury and inflammation, as corroborated by increased mRNA expression of kidney injury and inflammation markers, including Lcn2 (3.0 ± 0.54 vs. 1.0 ± 0.26 au; p =0.015), Havcr1 (5.3 ± 1.4 vs. 1.0 ± 0.3 au; p =0.024), Fn1 (1.6 ± 0.17 vs. 1.0 ± 0.19 au; p =0.068), Tnf (3.5 ± 0.71 vs. 1.0 ± 0.23 au; p =0.015), and Il1b (2.3 ± 0.44 vs. 1.0 ± 0.40 au; p =0.077). Costimulatory molecules on DCs provide the second signal required for effective T cell priming and promote clonal expansion of T cells. During NTS-induced CKD, Drp1 MKO kidneys exhibited increased numbers of CD86 + DCs (1.92 ± 0.17 vs. 1.15 ± 0.25 X10 4 /g; p=0.035) and T cells (20.2 ± 1.2 vs. 13.0 ± 1.7 X10 4 /g; p=0.01) compared to WT mice. Furthermore, Drp1 MKO kidneys had elevated numbers of effector memory T cells (CD44 hi CD62 lo , 10.01 ± 0.60 vs. 7.23 ± 0.98 X10 4 /g; p=0.047) and tissue-resident memory T cells (CD69 + , 6.63 ± 0.38 vs. 4.21 ± 0.39 X10 4 /g; p=0.002) compared to WT controls. These findings suggest that Drp1 in DCs protects against NTS-induced CKD by limiting DC-mediated T cell activation.
IntroductionSuccessful reperfusion does not always lead to good neurological outcomes and impaired microcirculation can be one of the underlying causes. Intra-arterial alteplase after mechanical thrombectomy (MT) may improve microcirculation contributing to neurological recovery, but prospective randomised studies are still needed to validate its efficacy and safety. We aim to assess the efficacy and safety of intra-arterial alteplase after MT for acute ischaemic stroke (AIS) with large-vessel occlusion (LVO).Methods and analysisTheIntra-arterial Alteplase for Acute Ischaemic Stroke After Mechanical Thrombectomy(PEARL) study is a multicentre, prospective, open-label, blinded-endpoint, randomised controlled trial. We consecutively screen AIS patients with anterior circulation LVO and National Institute of Health Stroke Scale of 6–25, who reach stable expanded Thrombolysis in Cerebral Infarction scores of 2b50-3 on angiography after MT. Eligible participants are 1:1 randomly assigned to the experimental group and the control group. Participants in the experimental group will receive intra-arterial alteplase (0.225 mg/kg and a maximum dose of 20 mg) after MT and standard medical treatment, while those in the control group will receive standard medical treatment alone after the procedure. The primary outcome is the proportion of patients with a 90-day modified Rankin scale of 0–1. A total of 324 participants are required to test the superiority hypothesis with 80% power at a two-tailed significance level of 0.05.Ethics and disseminationThis study has been approved by the Ethics Committee of Sun Yat-sen Memorial Hospital, Sun Yat-sen University (SYSKY-2023-390-02) and will be conducted following the Declaration of Helsinki. Ethical approvals have been obtained separately for all centres participating in the study. Study results will be published in peer-reviewed academic journals.Trial registration numberNCT05856851.