Wearable device-measured moderate to vigorous physical activity and risk of degenerative aortic valve stenosis.

BACKGROUND AND AIMS: Physical activity has proven effective in preventing atherosclerotic cardiovascular disease, but its role in preventing degenerative valvular heart disease (VHD) remains uncertain. This study aimed to explore the dose-response association between moderate to vigorous physical activity (MVPA) volume and the risk of degenerative VHD among middle-aged adults. METHODS: A full week of accelerometer-derived MVPA data from 87 248 UK Biobank participants (median age 63.3, female: 56.9%) between 2013 and 2015 were used for primary analysis. Questionnaire-derived MVPA data from 361 681 UK Biobank participants (median age 57.7, female: 52.7%) between 2006 and 2010 were used for secondary analysis. The primary outcome was the diagnosis of incident degenerative VHD, including aortic valve stenosis (AS), aortic valve regurgitation (AR), and mitral valve regurgitation (MR). The secondary outcome was VHD-related intervention or mortality. RESULTS: In the accelerometer-derived MVPA cohort, 555 incident AS, 201 incident AR, and 655 incident MR occurred during a median follow-up of 8.11 years. Increased MVPA volume showed a steady decline in AS risk and subsequent AS-related intervention or mortality risk, levelling off beyond approximately 300 min/week. In contrast, its association with AR or MR incidence was less apparent. The adjusted rates of AS incidence (95% confidence interval) across MVPA quartiles (Q1-Q4) were 11.60 (10.20, 13.20), 7.82 (6.63, 9.23), 5.74 (4.67, 7.08), and 5.91 (4.73, 7.39) per 10 000 person-years. The corresponding adjusted rates of AS-related intervention or mortality were 4.37 (3.52, 5.43), 2.81 (2.13, 3.71), 1.93 (1.36, 2.75), and 2.14 (1.50, 3.06) per 10 000 person-years, respectively. Aortic valve stenosis risk reduction was also observed with questionnaire-based MVPA data [adjusted absolute difference Q4 vs. Q1: AS incidence, -1.41 (-.67, -2.14) per 10 000 person-years; AS-related intervention or mortality, -.38 (-.04, -.88) per 10 000 person-years]. The beneficial association remained consistent in high-risk populations for AS, including patients with hypertension, obesity, dyslipidaemia, and chronic kidney disease. CONCLUSIONS: Higher MVPA volume was associated with a lower risk of developing AS and subsequent AS-related intervention or mortality. Future research needs to validate these findings in diverse populations with longer durations and repeated periods of activity monitoring.

Association of the stress hyperglycemia ratio with coronary artery disease complexity as assessed by the SYNTAX score in patients with acute coronary syndrome.

BACKGROUND: Mounting evidence supports a significant correlation between the stress hyperglycemia ratio (SHR) and both short- and long-term prognoses in patients with acute coronary syndrome (ACS). Nevertheless, research examining the association between the SHR and the complexity of coronary artery disease (CAD) is scarce. Therefore, this study aimed to explore the association between the SHR and CAD complexity, as assessed by the SYNTAX score, in patients with ACS. METHODS: A total of 4715 patients diagnosed with ACS were enrolled and divided into five groups according to the quintiles of the SHR. CAD complexity was assessed using the SYNTAX score and categorized as low (≤ 22) or mid/high (> 22) levels. Logistic regression was utilized to examine the association between the SHR and CAD severity (mid-/high SYNTAX score). Restricted cubic spline (RCS) curves were generated to assess the association between the SHR and CAD severity. Subgroup analyses were conducted to stratify outcomes based on age, sex, diabetes mellitus (DM) status, and clinical presentation. RESULTS: Among the total ACS population, 503 (10.7%) patients had mid/high SYNTAX scores. Logistic regression analysis revealed that the SHR was an independent risk factor for mid/high SYNTAX scores in a U-shaped pattern. After adjusting for confounding variables, Q1 and Q5 demonstrated elevated odds ratios (ORs) relative to the reference category Q3, with ORs of 1.61 (95% CI: 1.19 ∼ 2.19) and 1.68 (95% CI: 1.24 ∼ 2.29), respectively. Moreover, the ORs for Q2 (1.02, 95% CI: 0.73 ∼ 1.42) and Q4 (1.18, 95% CI: 0.85 ∼ 1.63) resembled that of Q3. Compared with the merged Q2-4 group, the ORs were 1.52 (95% CI: 1.21 ∼ 1.92) for Q1 group and 1.58 (95% CI: 1.25 ∼ 2) for the Q5 group. Subgroup analysis revealed that the U-shaped association between the SHR and mid/high SYNTAX score was attenuated in DM patients (P for interaction = 0.045). CONCLUSIONS: There were U-shaped associations between the SHR and CAD complexity in ACS patients, with an SHR ranging from 0.68 to 0.875 indicating a relatively lower OR for mid/high SYNTAX scores. Further studies are necessary to both evaluate the predictive value of the SHR in ACS patients and explore the underlying mechanisms of the observed U-shaped associations.

Prediction of hypoattenuating leaflet thickening in patients undergoing transcatheter aortic valves replacement based on clinical factors and 4D-computed tomography morphological characteristics: A retrospective cross-sectional study.

BACKGROUND: The rapid increase in the number of transcatheter aortic valve replacement (TAVR) procedures in China and worldwide has led to growing attention to hypoattenuating leaflet thickening (HALT) detected during follow-up by 4D-CT. It's reported that HALT may impact the durability of prosthetic valve. Early identification of these patients and timely deployment of anticoagulant therapy are therefore particularly important. METHODS: We retrospectively recruited 234 consecutive patients who underwent TAVR procedure in Fuwai Hospital. We collected clinical information and extracted morphological characteristics parameters of the transcatheter heart valve (THV) post TAVR procedure from 4D-CT. LASSO analysis was conducted to select important features. Three models were constructed, encapsulating clinical factors (Model 1), morphological characteristics parameters (Model 2), and all together (Model 3), to identify patients with HALT. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were plotted to evaluate the discriminatory ability of models. A nomogram for HALT was developed and verified by bootstrap resampling. RESULTS: In our study patients, Model 3 (AUC = 0.738) showed higher recognition effectiveness compared to Model 1 (AUC = 0.674, p = 0.032) and Model 2 (AUC = 0.675, p = 0.021). Internal bootstrap validation also showed that Model 3 had a statistical power similar to that of the initial stepwise model (AUC = 0.723 95%CI: 0.661-0.786). Overall, Model 3 was rated best for the identification of HALT in TAVR patients. CONCLUSION: A comprehensive predictive model combining patient clinical factors with CT-based morphology parameters has superior efficacy in predicting the occurrence of HALT in TAVR patients.

Multifunctional bispecific nanovesicles targeting SLAMF7 trigger potent antitumor immunity.

The effectiveness of immune checkpoint inhibitor (ICI) therapy is hindered by the ineffective infiltration and functioning of cytotoxic T cells and the immunosuppressive tumor microenvironment (TME). Signaling lymphocytic activation molecule family member 7 (SLAMF7) is a pivotal co-stimulatory receptor thought to simultaneously trigger natural killer (NK)-cell, T-cell, and macrophage antitumor cytotoxicity. However, the potential of this collaborative immune stimulation in antitumor immunity for solid tumors is under-explored due to the exclusive expression of SLAMF7 by hematopoietic cells. Here, we report the development and characterization of multifunctional bispecific nanovesicles targeting SLAMF7 and Glypican-3-a hepatocellular carcinoma (HCC)-specific tumor antigen. We found that by effectively "decorating" the surface of solid tumors with SLAMF7, these nanovesicles directly induced potent and specific antitumor immunity and remodeled the immunosuppressive TME, sensitizing the tumors to programmed cell death protein 1 (PD-1) blockade. Our findings highlight the potential of SLAMF7-targeted multifunctional bispecific nanovesicles as an anticancer strategy with implications for designing next-generation targeted cancer therapies.

Fish swim bladders as valve leaflets enhance the durability of transcatheter aortic valve replacement devices.

Transcatheter aortic valve replacement (TAVR) has emerged as an effective therapy for inoperable patients with severe aortic stenosis (AS). However, calcification-induced limited durability restricts its application. Fish swim bladders (FSB), which are resistant to calcific degeneration, offer a viable solution to this challenge. In this study, we developed a new TAVR device using FSB as the valve leaflet. Furthermore, the in vitro durability, in vivo performance, and size selection of this TAVR device were assessed by an experimental study and finite element analysis. A self-expandable TAVR device was fabricated by suturing the FSB films into a 23 mm nitinol alloy frame. Further, hemodynamic performance, such as effective orifice area, transvalvular pressure difference and regurgitant fraction, the durability was tested by the pulsatile flow test and accelerated fatigue test, according to the ISO 5840-3. The effect of release size on hydrodynamic performance was also investigated. Finally, the in vivo performance of the TAVR device were examined using a porcine implantation model. The results showed that the strength of the FSB films satisfied the requirements for valve leaflets. The hemodynamic performance of the FSB TAVR device met the requirements of ISO 5840-3 standards. After 400 million cycles, the FSB showed no fiber loss, torn, perforation, or other valve failure phenomena. In porcine models, the devices were well-positioned, functioned well with no stenosis immediately after the operation. Collectively, we successfully developed a TAVR device with FSB as valve leaflets that exhibited good fatigue resistance. STATEMENT OF SIGNIFICANCE: The source of material for the leaflets of commercialized biological heart valves (BHVs) is mainly bovine pericardium, but this material suffers the following problems: large and uneven thickness of the material, the presence of α-Gal and Neu5Gc antigens, and the susceptibility to structural valve degradation (SVD). New material for BHVs leaflets is rarely reported. In this study, we prepared a transcatheter aortic valve (TAV) and performed long-term in vitro and short-term in vivo studies using fish swim bladder (FSB) as the leaflets. The study confirmed that FSB TAV device can complete 400 million fatigue tests and maintain the good morphology of the leaflets, and that it still maintains good functionality after a certain amount of compression, indicating that FSB is a promising material for leaflets.

CycleTrans: Learning Neutral Yet Discriminative Features via Cycle Construction for Visible-Infrared Person Re-Identification.

Visible-infrared person re-identification (VI-ReID) is the task of matching the same individuals across the visible and infrared modalities. Its main challenge lies in the modality gap caused by the cameras operating on different spectra. Existing VI-ReID methods mainly focus on learning general features across modalities, often at the expense of feature discriminability. To address this issue, we present a novel cycle-construction-based network for neutral yet discriminative feature learning, termed CycleTrans. Specifically, CycleTrans uses a lightweight knowledge capturing module (KCM) to capture rich semantics from the modality-relevant feature maps according to pseudo anchors. Afterward, a discrepancy modeling module (DMM) is deployed to transform these features into neutral ones according to the modality-irrelevant prototypes. To ensure feature discriminability, another two KCMs are further deployed for feature cycle constructions. With cycle construction, our method can learn effective neutral features for visible and infrared images while preserving their salient semantics. Extensive experiments on SYSU-MM01 and RegDB datasets validate the merits of CycleTrans against a flurry of state-of-the-art (SOTA) methods, +1.88% on rank-1 in SYSU-MM01 and +1.1% on rank-1 in RegDB. Our code is available at https://github.com/DoubtedSteam/CycleTrans.

Diagnostic performance of intravascular ultrasound-based fractional flow reserve in evaluating of intermediate left main stenosis.

BACKGROUND: The recently introduced ultrasonic flow ratio (UFR), is a novel fast computational method to derive fractional flow reserve (FFR) from intravascular ultrasound (IVUS) images. In the present study, we evaluate the diagnostic performance of UFR in patients with intermediate left main (LM) stenosis. METHODS: This is a prospective, single center study enrolling consecutive patients with presence of intermediated LM lesions (diameter stenosis of 30%-80% by visual estimation) underwent IVUS and FFR measurement. An independent core laboratory assessed offline UFR and IVUS-derived minimal lumen area (MLA) in a blinded fashion. RESULTS: Both UFR and FFR were successfully achieved in 41 LM patients (mean age, 62.0 ± 9.9 years, 46.3% diabetes). An acceptable correlation between UFR and FFR was identified (r = 0.688, P < 0.0001), with an absolute numerical difference of 0.03 (standard difference: 0.01). The area under the curve (AUC) in diagnosis of physiologically significant coronary stenosis for UFR was 0.94 (95% CI: 0.87-1.01), which was significantly higher than angiographic identified stenosis > 50% (AUC = 0.66, P < 0.001) and numerically higher than IVUS-derived MLA (AUC = 0.82; P = 0.09). Patient level diagnostic accuracy, sensitivity and specificity for UFR to identify FFR ≤ 0.80 was 82.9% (95% CI: 70.2-95.7), 93.1% (95% CI: 82.2-100.0), 58.3% (95% CI: 26.3-90.4), respectively. CONCLUSION: In patients with intermediate LM diseases, UFR was proved to be associated with acceptable correlation and high accuracy with pressure wire-based FFR as standard reference. The present study supports the use of UFR for functional evaluation of intermediate LM stenosis.

The prognostic value of collateral circulation in coronary chronic total occlusion underwent percutaneous coronary intervention.

BACKGROUND: The prognostic value of coronary collateral circulation (CC) in patients undergoing chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is underdetermined. The purpose of the study was to assess the prognostic value of current two CC grading systems and their association with long-term outcomes in patients with CTO underwent PCI. METHODS: We consecutively enrolled patients with single-vessel CTO underwent PCI between January 2010 and December 2013. All patients were categorized into well-developed or poor-developed collaterals group according to angiographic Werner's CC (grade 2 vs. grade 0-1) or Rentrop (grade 3 vs. grade 0-2) grading system. The primary endpoint was 5-year cardiac death. RESULTS: Of 2452 enrolled patients, the overall technical success rate was 74.1%. Well-developed collaterals were present in 686 patients (28.0%) defined by Werner's CC grade 2, and in 1145 patients (46.7%) by Rentrop grade 3. According to Werner's CC grading system, patients with well-developed collaterals had a lower rate of 5-year cardiac death compared with those with poor-developed collaterals (1.6% vs. 3.3%, P = 0.02), those with suboptimal recanalization was associated with higher rate of 5-year cardiac death compared with optimal recanalization (4.7% vs. 0.8%, P = 0.01) and failure patients (4.7% vs. 1.6%, P = 0.12). However, the similar effect was not shown in Rentrop grading system. CONCLUSIONS: In patients with the single-vessel CTO underwent PCI, well-developed collaterals by Werner's CC definition were associated with lower rate of 5-year cardiac death. Werner's CC grading system had a greater prognostic value than Rentrop grading system in patients with CTO underwent PCI.

Contemporary spectrum, characteristics, and outcomes of adult patients with rheumatic valvular disease in China: Insights from the China-VHD study.

Background: Rheumatic valvular disease (RVD) represents a significant health concern in developing countries, yet a scarcity of detailed data exists. This study conducts a comprehensive examination of RVD patients in China, exploring aspects of the disease's spectrum, characteristics, investigation, management, and outcomes. Methods: The China Valvular Heart Disease (China-VHD) study, a nationwide, multicenter, prospective observational study, enrolled 13,917 adults with moderate-to-severe valvular heart disease from April to June 2018. Among these, 2402 patients with native RVD (19.7% of native VHD patients) were analyzed. Results: Among the RVD patients, the median age was 57 years (interquartile range 50-65), with 82.5% falling within the 40-70 age range; females were notably predominant (63.9%). Rheumatic etiology prevailed, particularly in southern regions (48.8%). Multivalvular involvement was observed in 47.4% of RVD cases, and atrial fibrillation emerged as the most common comorbidity (43.2%). Severe RVD affected 64.2% of patients. Valvular interventions were undertaken by 66.9% of RVD patients, predominantly involving surgical valve replacement (90.8%). Adverse events, encompassing all-cause mortality and heart failure hospitalization, occurred in 7.3% of patients during the 2-year follow-up. Multivariable analysis identified factors such as age, geographical region, low body mass index, renal insufficiency, left atrial diameter, and left ventricular ejection fraction <50% (all P < 0.05) associated with adverse events, with valvular intervention emerging as a protective factor (HR: 0.201; 95%CI: 0.139 to 0.291; p < 0.001). Conclusions: This study delivers a comprehensive evaluation of RVD patients in China, shedding light on the spectrum, characteristics, investigation, management, and outcomes of this prevalent condition.

Outcomes for patients undergoing transcatheter aortic valve replacement with ascending aorta dilation.

BACKGROUND: We aim to compare the short and long-term outcomes for aortic stenosis (AS) patients undergone TAVR with and without ascending aorta dilation (AAD). METHODS: Consecutive patients diagnosed with native severe AS who underwent TAVR from September 2012 to September 2021 were enrolled. They were stratified into the moderate/severe dilation group (greatest ascending aorta width ≥ 45 mm) and the non/mild dilation group. Survival outcomes were illustrated using Kaplan-Meier curves and evaluated with the log-rank test. Data from patients with CT follow-up of >6 months was used to investigate the progression rate of AAD. RESULTS: The study cohort comprised 556 patients, with a mean age of 75.5 ± 7.3 years. Among them, 107 patients (19.2%) had a moderate/severe AAD (≥45 mm), with an average diameter of 48.6 mm (±2.8). During hospitalization, both groups witnessed two cases of ascending aortic dissection (1.9% vs 0.4%, P = 0.380). The median follow-up duration was 3.9 years (95% CI: 3.8-4.0 years). No deaths were caused by aortic events and no patients experienced a new aortic dissection. The AAD cohort's 4-year all-cause and cardiovascular mortality rates were not significantly different to the non/mild dilation group's (log-rank test, P = 0.109 and P = 0.698, respectively). Follow-up CT data revealed that the rate of aortic dilation progression in the moderate/severe dilation group was not significantly different from that in the non/mild group (0.0 mm/year, 25-75%th: -0.3-0.2 vs 0.1 mm/year, 25-75%th: -0.3-0.4, P = 0.122). CONCLUSION: This study found no significant difference regarding short-term and long-term outcomes in AS patients with/without moderate/severe AAD undergoing TAVR.

Prolonged Dual Antiplatelet Therapy in Acute Myocardial Infarction Patients Without Revascularization: China Acute Myocardial Infarction Registry Study.

At least 12 months of dual antiplatelet therapy (DAPT) is 1 of the standards of care following percutaneous coronary intervention in patients with acute coronary syndrome. However, study on prolonged DAPT for patients with acute myocardial infarction (AMI) without revascularization is limited. We studied 1,744 patients with AMI without revascularization from the China Acute Myocardial Infarction registry between January 2013 and September 2014. These patients were on DAPT and did not experience AMI, stroke, or bleeding events at the 12-month follow-up. We divided them into 2 groups: 12-month DAPT group (DAPT for at least 12 months but <18 months) and 18-month DAPT group (DAPT for at least 18 months). The primary outcome was 24-month all-cause death. Overall, 1,221 patients (70.0%) took DAPT for ≥12 months but <18 months, whereas 523 patients (30.0%) took DAPT for ≥18 months. The proportion of patients at high ischemic risk and the proportion of patients at high bleeding risk were similar in the 2 groups. At 24 months, the all-cause mortality rate of the 18-month DAPT group was significantly lower than that for the 12-month DAPT group (3.7% vs 5.9%, p = 0.0471). The adjusted hazard ratio for all-cause death also showed statistical significance (0.59, 95% confidence interval 0.35 to 0.99, p = 0.0444). In conclusion, DAPT for at least 18 months appears to be associated with lower 24-month mortality for non-revascularization AMI patients without events within 12 months after onset.

Prognostic effect of stress hyperglycemia ratio on patients with severe aortic stenosis receiving transcatheter aortic valve replacement: a prospective cohort study.

BACKGROUND: Stress hyperglycemia ratio (SHR) has recently been recognized as a novel biomarker that accurately reflects acute hyperglycemia status and is associated with poor prognosis of heart failure. We evaluated the relationship between SHR and clinical outcomes in patients with severe aortic stenosis receiving transcatheter aortic valve replacement (TAVR). METHODS: There were 582 patients with severe native aortic stenosis who underwent TAVR consecutively enrolled in the study. The formula used to determine SHR was as follows: admission blood glucose (mmol/L)/(1.59×HbA1c[%]-2.59). The primary endpoint was defined as all-cause mortality, while secondary endpoints included a composite of cardiovascular mortality or readmission for heart failure, and major adverse cardiovascular events (MACE) including cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke. Multivariable Cox regression and restricted cubic spline analysis were employed to assess the relationship between SHR and endpoints, with hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 3.9 years, a total of 130 cases (22.3%) of all-cause mortality were recorded. Results from the restricted cubic spline analysis indicated a linear association between SHR and all endpoints (p for non-linearity > 0.05), even after adjustment for other confounding factors. Per 0.1 unit increase in SHR was associated with a 12% (adjusted HR: 1.12, 95% CI: 1.04-1.21) higher incidence of the primary endpoint, a 12% (adjusted HR: 1.12, 95% CI: 1.02-1.22) higher incidence of cardiovascular mortality or readmission for heart failure, and a 12% (adjusted HR: 1.12, 95% CI: 1.01-1.23) higher incidence of MACE. Subgroup analysis revealed that SHR had a significant interaction with diabetes mellitus with regard to the risk of all-cause mortality (p for interaction: 0.042). Kaplan-Meier survival analysis showed that there were significant differences in the incidence of all endpoints between the two groups with 0.944 as the optimal binary cutoff point of SHR (all log-rank test: p < 0.05). CONCLUSIONS: Our study indicates linear relationships of SHR with the risk of all-cause mortality, cardiovascular mortality or readmission for heart failure, and MACE in patients with severe aortic stenosis receiving TAVR after a median follow-up of 3.9 years. Patients with an SHR exceeding 0.944 had a poorer prognosis compared to those with lower SHR values.

Prevalence and impact of diabetes in patients with valvular heart disease.

This study aimed to investigate the prevalence of diabetes in valvular heart disease (VHD), as well as the relationship of diabetes with severity of valvular lesions and clinical outcome. A total of 11,862 patients with significant (≥moderate) VHD from the China Valvular Heart Disease study were included in the analysis. The primary outcome was the composite of all-cause death, hospitalization for heart failure, and myocardial infarction during two-year follow-up. The prevalence of diabetes was 14.5% (1,721/11,862) in VHD. After adjusting for patients' demographics, diabetes was associated with a significantly lower risk of severe valvular lesion in aortic regurgitation and mitral regurgitation (MR). In multivariable analysis, diabetes was identified as an independent predictor of two-year outcome in patients with MR (hazard ratio: 1.345, 95% confidence interval: 1.069-1.692, p = 0.011). More efforts should be made to enhance our understanding and improve outcomes of concomitant VHD and diabetes.

Pyroptotic Macrophage-Derived Microvesicles Accelerate Formation of Neutrophil Extracellular Traps via GSDMD-N-expressing Mitochondrial Transfer during Sepsis.

Macrophage pyroptosis and neutrophil extracellular traps (NETs) play a critical role in sepsis pathophysiology; however, the role of macrophage pyroptosis in the regulation of NETs formation during sepsis is unknown. Here, we showed that macrophages transfer mitochondria to neutrophils through microvesicles following pyroptosis; this process induces mitochondrial dysfunction and triggers the induction of NETs formation through mitochondrial reactive oxygen species (mtROS)/Gasdermin D (GSDMD) axis. These pyroptotic macrophage-derived microvesicles can induce tissues damage, coagulation, and NETs formation in vivo. Disulfiram partly inhibits these effects in a mouse model of sepsis. Pyroptotic macrophage-derived microvesicles induce NETs formation through mitochondrial transfer, both in vitro and in vivo. Microvesicles-mediated NETs formation depends on the presence of GSDMD-N-expressing mitochondria in the microvesicles. This study elucidates a microvesicles-based pathway for NETs formation during sepsis and proposes a microvesicles-based intervention measure for sepsis management.

Exploring the biomarkers and potential therapeutic drugs for sepsis via integrated bioinformatic analysis.

BACKGROUND: Sepsis is a life-threatening condition caused by an excessive inflammatory response to an infection, associated with high mortality. However, the regulatory mechanism of sepsis remains unclear. RESULTS: In this study, bioinformatics analysis revealed the novel key biomarkers associated with sepsis and potential regulators. Three public datasets (GSE28750, GSE57065 and GSE95233) were employed to recognize the differentially expressed genes (DEGs). Taking the intersection of DEGs from these three datasets, GO and KEGG pathway enrichment analysis revealed 537 shared DEGs and their biological functions and pathways. These genes were mainly enriched in T cell activation, differentiation, lymphocyte differentiation, mononuclear cell differentiation, and regulation of T cell activation based on GO analysis. Further, pathway enrichment analysis revealed that these DEGs were significantly enriched in Th1, Th2 and Th17 cell differentiation. Additionally, five hub immune-related genes (CD3E, HLA-DRA, IL2RB, ITK and LAT) were identified from the protein-protein interaction network, and sepsis patients with higher expression of hub genes had a better prognosis. Besides, 14 drugs targeting these five hub related genes were revealed on the basis of the DrugBank database, which proved advantageous for treating immune-related diseases. CONCLUSIONS: These results strengthen the new understanding of sepsis development and provide a fresh perspective into discriminating the candidate biomarkers for predicting sepsis as well as identifying new drugs for treating sepsis.

Randomised controlled trial of early magnetically controlled capsule endoscopy for the prevention of gastrointestinal bleeding in patients at high bleeding risk scheduled for percutaneous coronary intervention: MACE-GPS study protocol.

INTRODUCTION: Limited data are available regarding the decision-making process for preventing gastrointestinal bleeding in patients at high risk of bleeding scheduled for percutaneous coronary intervention (HBPCI), especially due to the lack of a simple, accurate and sensitive methods for gastrointestinal injury detection. This randomised trial aims to assess the effects of early magnetically controlled capsule endoscopy (MCE) in patients with HBPCI for the prevention of gastrointestinal bleeding compared with conventional management. METHODS AND ANALYSIS: The Magnetic-Assisted Capsule Endoscopy Gastrointestinal bleeding Protection Strategy (MACE-GPS) is a multicentre, open-label, randomised controlled trial. Patients admitted for HBPCI will be randomised and placed into two study groups. In the early MCE group, 1228 patients will undergo MCE following admission to the hospital. If necessary, these patients may further undergo a multidisciplinary approach to determine treatment based on the MCE findings. A total of 1228 patients in the control group will undergo conventional treatment based on the attending cardiologist's interpretation of their clinical presentations. The primary end point is the incidence of gastrointestinal bleeding within 12 months of enrolment. ETHICS AND DISSEMINATION: The MACE-GPS trial has been approved by the ethics committees of all participating sites. Participant recruitment began in April 2023 and will be completed in April 2025, and the 1-year follow-up will be completed in April 2026. The study results will be disseminated through conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ChiCTR2300070025.

Diagnostic performance of ultrasonic flow ratio versus quantitative flow ratio for assessment of coronary stenosis.

BACKGROUND: Ultrasonic flow ratio (UFR) is a novel intravascular ultrasound (IVUS)-derived modality for fast computation of fractional flow reserve (FFR) without pressure wires and adenosine. AIMS: This study was sought to compare the diagnostic performance of UFR and quantitative flow ratio (QFR), using FFR as the reference standard. METHODS: This is a retrospective study enrolling consecutive patients with intermediate coronary artery lesions (diameter stenosis of 30%-90% by visual estimation) for IVUS and FFR measurement. UFR and QFR were performed offline in a core-lab by independent analysts blinded to FFR. RESULTS: From December 2022 to May 2023, a total of 78 eligible patients were enrolled. IVUS and FFR measurements were successfully conducted in 104 vessels, finally 98 vessels with both FFR, UFR and QFR evaluation were analyzed. Mean FFR was 0.79 ± 0.12. UFR showed a strong correlation with FFR similar to QFR (r = 0.83 vs. 0.82, p = 0.795). Diagnostic accuracy of UFR was non-inferior to QFR (94% [89%-97%] versus 90% [84%-94%], p = 0.113). Sensitivity and specificity in identifying hemodynamically significant stenosis were comparable between UFR and QFR (sensitivity: 89% [79%-96%] versus 85% [74%-92%], p = 0.453; specificity: 97% [91%-99%] versus 95% [88%-99%], p = 0.625). The area under curve for UFR was 0.95 [0.90-0.98], non-inferior to QFR (difference = 0.021, p = 0.293), and significantly higher than minimum lumen area (MLA; difference = 0.13, p < 0.001). Diagnostic accuracy of UFR and QFR was not statically different in bifurcation nor non-bifurcation lesions. CONCLUSIONS: UFR showed excellent concordance with FFR, non-inferior to QFR, superior to MLA. UFR provides a potentiality for the integration of physiological assessment and intravascular imaging in clinical practice.

TREM-2 Drives Development of Multiple Sclerosis by Promoting Pathogenic Th17 Polarization.

Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease, mediated by pathogenic T helper 17 (Th17) cells. However, the therapeutic effect is accompanied by the fluctuation of the proportion and function of Th17 cells, which prompted us to find the key regulator of Th17 differentiation in MS. Here, we demonstrated that the triggering receptor expressed on myeloid cells 2 (TREM-2), a modulator of pattern recognition receptors on innate immune cells, was highly expressed on pathogenic CD4-positive T lymphocyte (CD4+ T) cells in both patients with MS and experimental autoimmune encephalomyelitis (EAE) mouse models. Conditional knockout of Trem-2 in CD4+ T cells significantly alleviated the disease activity and reduced Th17 cell infiltration, activation, differentiation, and inflammatory cytokine production and secretion in EAE mice. Furthermore, with Trem-2 knockout in vivo experiments and in vitro inhibitor assays, the TREM-2/zeta-chain associated protein kinase 70 (ZAP70)/signal transducer and activator of transcription 3 (STAT3) signal axis was essential for Th17 activation and differentiation in EAE progression. In conclusion, TREM-2 is a key regulator of pathogenic Th17 in EAE mice, and this sheds new light on the potential of this therapeutic target for MS.

NLRP12 Senses the SARS-CoV-2 Membrane Protein and Promotes an Inflammatory Response.

COVID-19 is an acute respiratory disorder that is caused by SARS-CoV-2, in which excessive systemic inflammation is associated with adverse patient clinical outcomes. Here, we observed elevated expression levels of NLRP12 (nucleotide-binding leucine-rich repeat-containing receptor 12) in human peripheral monocytes and lung tissue during infection with SARS-CoV-2. Co-immunoprecipitation analysis revealed that NLRP12 directly interacted with the M protein through its leucine-rich repeat domain. Moreover, in vitro studies demonstrated that NLRP12 interacted with TRAF3 and promoted its ubiquitination and degradation, which counteracted the inhibitory effect of TRAF3 on the NF-κB/MAPK signaling pathway and promoted the production of inflammatory cytokines. Furthermore, an in vivo study revealed that NLRP12 knockout mice displayed attenuated tissue injury and ameliorated inflammatory responses in the lungs when infected with a SARS-CoV-2 M protein-reconstituted pseudovirus and mouse coronavirus. Taken together, these findings suggest that NLRP12 mediates the inflammatory responses during coronavirus infection.