Lumen Stenosis Research Articles

Evaluation of Intensive Statins and Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors on Intracranial Artery Plaque Stability: A Prospective Single-Arm Study.

Intracranial atherosclerotic stenosis is a leading cause of ischemic stroke and recurrent events due to plaque instability. High-resolution magnetic resonance imaging identifies plaque enhancement as a key marker of instability. This study evaluated the efficacy of combined high-intensity statins and proprotein convertase subtilisin/kexin type 9 inhibitors in plaque stabilization. In this prospective, single-arm study, patients with acute stroke and intracranial atherosclerotic stroke in the M1 segment of the middle cerebral artery or basilar artery were enrolled. After 24 weeks of intensive statin and evolocumab therapy, high-resolution magnetic resonance imaging assessments of intracranial vessels were conducted at baseline and follow-up. The primary end point was the change in stenosis degree; secondary end points included changes in plaque enhancement (contrast ratio) and plaque burden. Thirty-six patients (median age, 58 years) participated. After therapy, stenosis decreased from 75.9% (interquartile range, 69.5%-84.8%) to 65.3% (interquartile range, 53.8%-75.0%; P<0.001). Contrast ratio grades and contrast volume decreased significantly (P<0.001), and lumen area increased (from 1.03 mm2 [interquartile range, 0.59-1.72 mm2] to 2.08 mm2 [interquartile range, 1.00-3.10 mm2]; P<0.001). No significant changes were observed in wall area, wall area index, or remodeling index. A notable correlation between the decrease in low-density lipoprotein cholesterol/apolipoprotein B ratio and reduction in contrast volume was observed. Combining proprotein convertase subtilisin/kexin type 9 inhibitors with high-intensity statins may improve plaque stability and reduce lumen stenosis in patients with intracranial atherosclerotic stenosis. Larger randomized controlled trials are needed to confirm these findings. URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2200058029.

PAC1 Agonist Maxadilan Reduces Atherosclerotic Lesions in Hypercholesterolemic ApoE-Deficient Mice.

A possible involvement of immune- and vasoregulatory PACAP signaling at the PAC1 receptor in atherogenesis and plaque-associated vascular inflammation has been suggested. Therefore, we tested the PAC1 receptor agonist Maxadilan and the PAC1 selective antagonist M65 on plaque development and lumen stenosis in the ApoE-/- atherosclerosis model for possible effects on atherogenesis. Adult male ApoE-/- mice were fed a cholesterol-enriched diet (CED) or standard chow (SC) treated with Maxadilan, M65 or Sham. Effects of treatment on atherosclerotic plaques, lumen stenosis, apoptosis and pro-inflammatory signatures were analyzed in the brachiocephalic trunk (BT). The percentage of Maxadilan treated mice exhibiting plaques under SC and CED was lower than that of Sham or M65 treatment indicating opposite effects of Maxadilan and M65. Maxadilan application inhibited lumen stenosis in SC and CED mice compared to the Sham mice. In spite of increased cholesterol levels, lumen stenosis of Maxadilan-treated mice was similar under CED and SC. In contrast, M65 under SC or CED did not reveal a significant influence on lumen stenosis. Maxadilan significantly reduced the TNF-α-immunoreactive (TNF-α+) area in the plaques under CED, but not under SC. In contrast, the IL-1β+ area was reduced after Maxadilan treatment in SC mice but remained unchanged in CED mice compared to Sham mice. Maxadilan reduced caspase-3 immunoreactive (caspase-3+) in the tunica media under both, SC and CED without affecting lipid content in plaques. Despite persistent hypercholesterolemia, Maxadilan reduces lumen stenosis, apoptosis and TNF-α driven inflammation. Our data suggest that Maxadilan provides atheroprotection by acting downstream of hypercholesterolemia-induced vascular inflammation. This implicates the potential of PAC1-specific agonist drugs against atherosclerosis even beyond statins and PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors.

Treatment of a staple-line leak after laparoscopic sleeve gastrectomy using an esophagoduodenal Niti-S Mega-stent.

A 56-year-old female with class 3 obesity, was previously submitted to laparoscopic sleeve gastrectomy (LSG) two weeks before current admission. The patient was admitted due to fever, abdominal pain and vomiting. CT revealed a 13.5cm collection between the gastric wall and left hepatic lobe. Piperacillin-Tazobactam was initiated, and percutaneous drainage of the purulent collection was performed. The upper endoscopy showed pus in the gastric lumen and a 10-mm leak at the esophago-gastric junction with contrast extravasation. Argon plasma coagulation (40W, 2L/min) was applied at the orifice margins to promote healing. After 0,038'' guidewire placement through the proximal jejunum, a Niti-S™-MEGA™ (Mega-Stent) 28x230mm (Taewoong Medical™) was deployed under fluoroscopic control. CT at 72h showed absence of leakage. Oral nutrition was started uneventfully. Ambulatory endoscopy was scheduled for eight weeks later to remove the stent, which was easily accomplished with a foreign body forceps. Granulation tissue was observed in the previous leak location and no extraluminal contrast was observed at fluoroscopic evaluation, confirming complete healing and successful endoscopic treatment. Three weeks after stent removal, the patient presented with dysphagia. Upper endoscopy revealed a short and narrowed lumen stenosis at 28cm from the incisives, which was easily manage through TTS balloon dilation. No additional complications were observed.

Simulation of Blood Flow in Arteries for Functional Assessment of Coronary Disease: Implementation of Numerical Code

Cardiovascular diseases are a major cause of mortality and morbidity in developed countries. Coronary atherosclerotic disease (CAD) is a degenerative process that is characterized by the development of atheromatous plaques on the wall of coronary arteries. Clinical manifestations of CAD range from stable angina, resulting from progressive plaque growth with partial obstruction of the arterial lumen (stenosis) and consequent limitation of coronary blood flow. In clinical practice, a diagnostic strategy is widely used to assess the functional relevance of CAD: the invasive assessment of myocardial fractional flow reserve (FFR).Coronary Computed Tomography Angiography (CTA) is an established non-invasive diagnostic tool for evaluating CAD. However, CTA can overestimate anatomic stenosis and is limited in that it does not provide information on the hemodynamic relevance of coronary stenosis. Thus, the implementation and numerical simulation of blood flow in arteries in the most real physiological conditions has been one of the main areas of interest of the authors [1]. The main purpose of this work is to develop and validate a computational tool for calculating the FFR and hemodynamic descriptors.In this way, to obtain the most accurate non-invasive FFR, the hemodynamic numerical tool was hardly improved to establish real conditions, specific to each patient case with CAD. Therefore, to achieve accurate pressures, Windkessel models, mainly based on the resistance of blood flow [2], were implemented considering hyperemia conditions (maximal dilation of the coronary tree), since the patient must be subjected to this condition during the catheterization to obtain the invasive FFR (reference value for validation). Moreover, the 3D patient-specific geometry of the artery was modified to simulate blood flow in hyperemic conditions. The numerical code development was performed in ANSYS® software.After validation, the authors aim to create a software for local use, allowing a comprehensive assessment of CAD in an accessible, fast, reliable, and non-invasive way. [1] Pinto, S.I.S. et al. (2020). The impact of non-linear viscoelastic property of blood in right coronary arteries hemodynamics – a numerical implementation. International Journal of Non-Linear Mechanics 123, 103477.[2] Boileau, E. et al. (2018) Estimating the accuracy of a reduced-order model for calculation of fractional flow reverse (FFR). Int J Numer Meth Biomed Engng 34, e2908.

Endoscopic retrograde appendicitis therapy formanagement ofchronic fecalith appendicitis.

Chronic appendicitis is a condition with chronic abdominal pain or mild attacks of appendicitis, seriously affecting the patient's quality of life. Endoscopic retrograde appendicitis therapy (ERAT) has emerged as a promising, non-invasive treatment for acute uncomplicated appendicitis. Here, we aim to assess the safety and efficacy of ERAT for chronic fecalith appendicitis. We retrospectively reviewed the medical records of consecutive patients who underwent ERAT for chronic fecalith appendicitis at Zhongshan Hospital, Fudan University, Shanghai, China between December 2017 and June 2023. Clinicopathological characteristics, procedure-related parameters, AEs, and follow-up outcomes were analyzed. A total of 60 patients were included. ERAT intubation was successfully performed in all patients (100%). The median procedure time was 15min (IQR, 12-25min). The postoperative abdominal pain scores were significantly reduced (P < 0.0001). Short-term adverse events included 5 cases of abdominal pain (8.3%) and 2 cases of fever (3.3%). Long-term adverse events included recurrent abdominal pain in 3 cases (5.0%) and recurrent appendicitis in 2 cases (3.3%). The median time to recurrence was 5months (IQR, 2-12months). Logistic regression analysis revealed appendiceal stenosis (OR 25.000, 95% CI 1.114-561.281, P = 0.043) and distorted appendix lumen (OR 12.500, 95% CI 1.373-113.806, P = 0.025) as significant risk factors for long-term adverse events. ERAT may be a safe, effective and minimally invasive alternative approach for chronic fecalith appendicitis. Appendix lumen stenosis and distortion are risk factors of recurrence. Further large-scale prospective studies are necessary to assess the efficacy and safety of ERAT compared with antibiotic therapy and surgery.

Advancements in imaging of intracranial atherosclerotic disease: beyond the arterial lumen to the vessel wall.

Intracranial atherosclerotic disease (ICAD) significantly increases the risk of ischemic stroke. It involves the accumulation of plaque within arterial wallsandnarrowing or blockage of blood vessel lumens. Accurate imaging is crucial for the diagnosis and management of ICAD at both acute and chronic stages. However, imaging the small, tortuous intracranial arterial walls amidstcomplex structures is challenging. Clinicians have employed diverse approaches to improve imaging quality, with a particular emphasis on optimizing the acquisition ofimages using newtechniques, enhancing spatial and temporal resolution of images, and refining post-processing techniques. ICAD imaging has evolved from depicting lumen stenosis to assessing blood flow reserve and identifying plaque components. Advanced techniques such as fractional flowreserve (FFR), high-resolution vessel wall magnetic resonance (VW-MR), optical coherence tomography (OCT), and radial wall strain (RWS) now allow direct visualization offlow impairment, vulnerable plaques, and blood flow strainto plaque, aiding in the selection of high-risk strokepatients for intervention. This article reviews the progression of imaging modalities from lumen stenosis to vessel wall pathology and compares their diagnostic value forrisk stratification in ICAD patients.

Abstract 4138602: Effect of Left Ventricular Ejection Fraction On Computed Tomography-Derived Fractional Flow Reserve Diagnostic Accuracy For Significant Coronary Artery Disease

Background: Coronary Computed Tomography Angiography (CCTA) and CT-derived fractional flow reserve (CT-FFR) accurately assess the severity of coronary artery disease. However, the diagnostic accuracy of CT-FFR in patients with low left ventricular ejection fraction (LVEF) is unknown. Goal: Describe the per-vessel diagnostic performance of CT-FFR to detect significant coronary disease in patients with normal and reduced LVEF by echocardiogram. Methods: This was a retrospective study of 441 patients who underwent CCTA and CT-FFR at the UMass Memorial Health System between 2020 and 2023. Those with echocardiogram and invasive coronary angiography were analyzed and divided in two groups based on two-dimensional LVEF: those with LVEF &lt; 55%, and with LVEF ≥ 55%. We excluded those with prior coronary stents, incomplete CCTA, CT-FFR data due to artifacts, or poor-quality echocardiographic images. CT-FFR ≤ 0.8 was considered abnormal. Significant coronary disease by invasive angiography (reference standard) was defined as lumen stenosis ≥ 70% (left main ≥ 50%), or abnormal physiologic characteristics by FFR, resting full-cycle ratio, or instantaneous wave-free ratio. Results: 222 coronary vessels (102 patients) were analyzed. Of 102 vessels (44%) with significant coronary artery disease, 55 (53.9%) were treated with percutaneous coronary intervention, and 25 (24.5%) with coronary artery bypass grafting. Overall, CT-FFR sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 86.7% (95%CI 78.3-92.7), 75.0% (95%CI 66.4-82.3), 73.2% (95%CI 66.6-78.9), 87.7% (95%CI 81.0-92.3), and 80.1% (95%CI 74.3-85.2), respectively. 37 vessels corresponded to patients with LVEF &lt; 55%, and 185 to those with LVEF ≥ 55%. Diagnostic accuracy in both groups is seen in table 1. Conclusions: Low-normal and reduced LVEF adversely affects the diagnostic performance of CT-FFR, by reducing sensitivity, and slightly increasing specificity.

Abstract 4138322: Do branched stent grafts for dissecting aortic aneurysms really improve long-term outcomes?

Backgrounds: We have previously used a handmade branched stent graft (SG) to treat thoracic aortic aneurysms. In this study, we examined the long-term results of treatment for dissecting thoracic aortic aneurysms. Methods: Between 2004 and 2014, we treated 28 patients with dissecting thoracic aneurysms using the branched SGs. Results: The mean age was 65 ± 14 years; 17 were over 70, and 22 were male. The mean time from the onset of dissection was 5.7 ± 6.3 years; 6 were operated within one year. The mean aneurysm diameter was 59 ± 8 mm. All dissecting aneurysms were located after zone 3. SG branches were one in 24 cases, two in 2, and three in 2. Twenty-two were treated for entry closure and distal landing in the true lumen. Six with limited dissecting aneurysms were treated for entry closure and distal landing in a non-dissected lumen. The cause of perioperative death was pneumonia in 1. The mean follow-up was 8.3 ± 5.3 years. Entry closure was achieved at 86%, branch patency was 94%, and aneurysm diameter was reduced by an average of 5 ± 14%. There were 6 aneurysm-related deaths. Two were aneurysm ruptures, and each of the 4 was additional operative death, sudden death, SMA occlusion, and type A dissection. The aneurysm-related mortality was 26% at eight years; there was no difference between under 70 and over 70 years old. The cumulative risk of additional procedures was 57% at eight years, and the risk was higher in those over 70 than those under 70 (p&lt;0.05). Thirteen required additional procedures, and 5 required multiple. In detail, re-TEVAR to distal SINE was in 7, re-TEVAR for aneurysm enlargement due to residual false lumen was in 1, re-TEVAR for type 1a endoleak (EL) was in 4, open repair was in 3, stenting for stenosis of true lumen in iliac artery was in 1, stenting for SG branches were in 2, and embolization of the left subclavian artery after re-TEVAR was in 1. Details of open repair were partial arch and thoracic descending replacement for type 1a EL in 1, ascending and partial arch replacement for type 1a EL followed by partial arch and thoracoabdominal replacement in 1, partial arch and thoracoabdominal replacement for distal SINE and aneurysm enlargement in 1. Conclusion: The branched SG for dissecting thoracic aneurysms successfully achieved the initial goal of entry closure, which concept is promising, but requires careful observation for appropriate additional procedures.

Intravascular enhancement sign at 3D T1-weighted turbo spin echo sequence is associated with cerebral atherosclerotic stenosis

ObjectiveIntravascular enhancement sign (IVES) at three-dimensional T1-weighted turbo spin echo (3D T1W TSE) sequence may be a simple hemodynamic maker. This study aims to investigate the association between IVES and features of intracranial atherosclerotic stenosis (ICAS). MethodRetrospective analysis of clinical and imaging data of patients who underwent high resolution-vessel wall imaging (HR-VWI) examination from May 2021 to May 2023. The number of IVES vessels and ICAS features at HR-VWI were extracted by two neuroradiologists. Paired comparisons and correlation analysis on these indicators were performed. ResultsA total of 118 patients with ICAS in the first segment of the middle cerebral artery and accompanied by unilateral IVES were enrolled. Compared to the non-IVES side, a higher incidence of ischemic events and intraplaque hemorrhage (IPH), higher degree of vascular stenosis and enhancement, lower remodeling index, and lower signal intensity ratio (SIR) were found in subjects with IVES. In the ICAS with IVES, 79.66 % showed severe stenosis and occlusion; in the ICAS with severe stenosis and occlusion, 89.5 % showed IVES in the distal. A multivariable logistic regression model identified the vascular stenosis degree (OR = 1.922; 95 %CI [1.37–2.692]; P < 0.001), enhanced-degree (OR = 2.486; 95 %CI [1.315–4.698]; P = 0.005), position (OR = 2.869; 95 %CI [1.255–6.560]; P = 0.012), and SIR (OR = 0.032; 95 %CI [0.004–0.275]; P = 0.002) were independent association with the presence of IVES. The area under the curve was 0.911 for the use of IVES vessel quantities to identify severe stenosis and occlusion of arterial lumen. ConclusionThe number of IVES vessels was associated with the local features of ICAS, which may indicate severe stenosis and occlusion in the major branches of the proximal artery.

Effects of molecular interaction and liver sinusoidal mechanical properties on leukocyte adhesions

It is interesting to find pathologically that leukocytes, especially neutrophils, tend to adhere in the liver sinusoids dominantly but not in the post-sinusoidal venules. While both views of receptor-ligand interactions and physical trapping are proposed for mediating leukocyte adhesion in liver sinusoids, integrated investigations for classifying their respective contributions are poorly presented. With a combination of Monte Carlo simulation and immersed boundary method (IBM), this study explored numerically the effects of molecular interaction kinetics and sinusoidal mechanical properties on leukocyte adhesion in liver sinusoid jointly. Results showed that, within the range of biological limitations, the lumen stenosis ratio, leukocyte stiffness, Disse space stiffness and endothelium permeability regulate the comprehensive adhesion process in a descending order of significance in the presence of receptor-ligand interactions. While leukocyte adhesions could be mutually promoted with proper combinations of leukocyte stiffness, lumen stenosis, and molecular interaction, the binding affinity is insensitive under the conditions with low leukocyte stiffness in normal lumen stenosis and high leukocyte stiffness in high lumen stenosis. This work deepened the understanding of recruitment mechanism of leukocyte in liver sinusoids.

Impact of ultra-high-resolution on cardiac CT assessment of coronary artery stenoses, plaque burden/composition, and pericoronary adipose tissue attenuation

Abstract Background Conventional coronary computed tomography angiography (CCTA) overestimates stenoses within stents and calcified arteries due to "blooming" artifacts. Ultra-high-resolution coronary CT (UHR-CT) may overcome this limitation because of higher spatial resolution. Purpose To investigate differences in coronary arterial lumen volume, stenosis severity, and plaque composition, between CCTA and UHRCT in patients with stents and/or high coronary calcium scores. Methods As part of a prospective pilot study, 14 patients referred for invasive coronary angiography for evaluation of obstructive CAD underwent UHRCT (Canon Precision, 160 x 0.25mm slices) prior to catheterization. Images of identical cardiac phases were reconstructed in two badges for comparison: 1) Ultra-high resolution using a 1,024 x 1,024 matrix, 0.25 mm, and 2) conventional resolution with a 524 x 524 matrix, 0.5 mm. All images were reconstructed using iterative reconstruction algorithm (AIDR 3D) and a sharp kernel (FC05). For the left main and three coronary arteries, an automated contour analysis using a dedicated software (QAngioCT RE 3.2, Medis, Netherlands) was performed to compare conventional CCTA vs. UHR-CT resolution images across common vascular and plaque metrics, including lumen and vessel volume, plaque burden/volume, plaque composition based upon predefined fixed intensity cut-off values of CT attenuation, minimal and maximal plaque thickness, pericoronary adipose tissue attenuation (PCAT), minimal lumen area and diameter, and diameter stenosis. All lumen and vessel contours were generated by the software, without manual editing. The segment model proposed by the SCCT was used as reference and the lesions classified as greater than 25% stenosis by visual assessment were recorded. The quality of the images was subjectively assessed using a 5-point Likert scale. Vessel segments with scores 1 (severe artifacts) and 2 (pronounced artifacts) were not included in the analysis. Results The mean patient age was 68.5 years (±6.8), 2 were female (14.3%), 6 patients had stents (11 stented segments) and the mean Agatston score was 947.6 (±449) among the 8 non-stented patients. A total of 56 vessels, 133 segments, and 57 lesions were analyzed. Eight segments (6%) were excluded from the analysis due to poor quality. Results on a per segment and per lesion basis were summarized in the table. The mean PCAT value was significantly lower for the UHRCT images compared to NR reconstruction in both segment (p&amp;lt;0.001) and lesion based (p=0.002) analyses. Plaque differentiation varied by UHRCT resulted in a lower fibrous plaque volumes but higher necrotic (low attenuation) plaque volumes. Conclusions Ultra-high-resolution CT image analysis results in significantly different coronary artery plaque volume and PCAT assessment vs. conventional resolution CCTA. These findings have implications for evaluating high-risk plaque features and perivascular inflammation in patients.Table 1

Clinical characteristics of HIV-associated tracheobronchial Talaromyces marneffei infection in seven patients in Guangxi, China.

Tracheobronchial Talaromyces marneffei (T. marneffei) infections among HIV-infected patients are rare. To improve understanding, we analyzed the clinical features, immune mechanisms, treatment, and prognosis of these patients. We collected clinical information from HIV-positive patients with talaromycosis admitted to the Fourth People's Hospital of Nanning from January 2015 to June 2022. Patients who presented with culture and/or histopathological proof of tracheobronchial T. marneffei infection were included. A total of 108 patients with respiratory infections who underwent bronchoscopy were enrolled. Seven patients with tracheobronchial T. marneffei infection, all of whom were men with a median age of 48 years (range 39-50 years), were analyzed. Cough, sputum, fever, and weight loss were the most common symptoms. The total white blood cell count was normal or decreased, and all lymphocyte counts were decreased. All patients had reduced CD4+ T-cell counts, with values less than 50 cells/µL. The chest CT imaging signs included patchy signals or large areas of exudation, bronchial stenosis and occlusion. This was different from the lack of bronchial involvement. Endoscopically, the trachea and bronchial mucosa showed congestion, edema, surface attachment, nodules, lumen stenosis, obstruction, etc. T. marneffei spores were found via bronchial mucosal pathology in all 7 patients. Five patients were initially treated with intravenous infusion of amphotericin B for 2 weeks, followed by oral itraconazole capsules (200mg) twice daily, and two patients were initially treated with itraconazole. Six patients were remission, and 1 died. The clinical features of trachea invasion and nontracheal invasion are not unique, but chest CT reveals manifestations such as masses, solid shadows, and bronchial stenosis/obstruction. Bronchoscopy should be performed if possible, and the presence or absence of trachea T. marneffei infection should be confirmed. Antiviral therapy combined with antifungal therapy can improve patient prognosis.

Irisin suppresses PDGF-BB-induced proliferation of vascular smooth muscle cells in vitro by activating AMPK/mTOR-mediated autophagy.

Restenosis is a pivotal factor that restricts the efficacy of coronary artery bypass grafting. Inhibition of vascular smooth muscle cells (VSMCs) proliferation can improve intimal hyperplasia and lumen stenosis. Irisin, a polypeptide secreted by muscle cells, has been demonstrated to have a protective role in various cardiovascular diseases. However, the effect and mechanism of irisin on VSMCs proliferation and phenotype switching remain unclear. Cell proliferation ability was assessed using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and 5-ethynyl-2'-deoxyuridine (EdU) incorporation. Cell cycle analysis was performed using flow cytometry, while expression levels of contractile and synthesis-related proteins were determined through RT-qPCR and Western blot. The VSMCs were infected with an adenovirus carrying GFP-LC3, and the proportion of cells showing positive expression was assessed. Additionally, the formation of autophagic lysosomes in cells was observed through transmission electron microscopy. In this study, we have demonstrated the inhibitory effects of irisin on the proliferation and phenotypic transition of platelet-derived growth factor-BB (PDGF-BB)-induced VSMCs. More importantly, we have discovered that irisin can activate the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway to mediate autophagy in PDGF-BB-induced VSMCs. The inhibitory effect of irisin on PDGF-BB-induced VSMCs proliferation was significantly attenuated by the AMPK inhibitor, Compound C. Conversely the mTOR inhibitor, rapamycin further enhanced the inhibitory effect of irisin on PDGF-BB induced VSMCs proliferation. In conclusion, our findings suggest that irisin effectively suppresses the aberrant proliferation of VSMCs following PDGF-BB stimulation by modulating autophagy levels through the AMPK/mTOR signaling pathway.

Silencing of PCK1 mitigates the proliferation and migration of vascular smooth muscle cells and vascular intimal hyperplasia by suppressing STAT3/DRP1-mediated mitochondrial fission.

The pathological proliferation and migration of vascular smooth muscle cells (VSMCs) are key processes during vascular neointimal hyperplasia (NIH) and restenosis. Phosphoenolpyruvate carboxy kinase 1 (PCK1) is closely related to a variety of malignant proliferative diseases. However, the role of PCK1 in VSMCs has rarely been investigated. This study aims to examine the role of PCK1 in the proliferation and migration of VSMCs and vascular NIH after injury. In vivo, extensive NIH and increased expression of PCK1 within the neointima are observed in injured arteries. Interestingly, the administration of adeno-associated virus-9 (AAV-9) carrying Pck1 short hairpin RNA (sh Pck1) significantly attenuates NIH and stenosis of the vascular lumen. In vitro, Pck1 small interfering RNA (si Pck1)-induced PCK1 silencing inhibits VSMC proliferation and migration. Additionally, silencing of PCK1 leads to reduced expression of dynamin-related protein 1 (DRP1) and attenuated mitochondrial fission. Lentivirus-mediated DRP1 overexpression markedly reverses the inhibitory effects of PCK1 silencing on VSMC proliferation, migration, and mitochondrial fission. Finally, PCK1 inhibition attenuates the phosphorylation of signal transducer and activator of transcription 3 (STAT3). Activation of STAT3 abolishes the suppressive effects of PCK1 silencing on DRP1 expression, mitochondrial fission, proliferation, and migration in VSMCs. In conclusion, PCK1 inhibition attenuates the mitochondrial fission, proliferation, and migration of VSMCs by inhibiting the STAT3/DRP1 axis, thereby suppressing vascular NIH and restenosis.

Are Hair Scalp Trace Elements Correlated with Atherosclerosis Location in Coronary Artery Disease?

Coronary artery disease is among the leading current epidemiological challenges. The genetic, clinical, and lifestyle-related risk factors are well documented. The reason for specific epicardial artery locations remains unsolved. The coronary artery topography and blood flow characteristics may induce local inflammatory activation. The atherosclerotic plaque formation is believed to represent inflammatory response involving enzymatic processes co-factored by trace elements. The possible relation between trace elements and coronary artery disease location was the subject of the study. There were 175 patients (107 (61) men and 68 (39) females) in a median (Q1-3) age of 71years (65-76) admitted for coronary angiography due to chronic coronary syndrome. The angiographic results focused on the percentage of lumen stenosis in certain arteries and were compared with the results for hair scalp trace elements. The correlation between left main coronary artery atherosclerotic plaques and nickel (Ni), zinc (Zn), and antimony (Sb) hair scalp concentration was noted. The analysis revealed a positive relation between left descending artery disease and chromium (Cr), sodium (Na), arsenic (As), and molybdenum (Mo) and a negative correlation with strontium (Sr). The atherosclerotic lesion in the circumflex artery revealed correlations in our analysis with sodium (Na), potassium (K), chromium (Cr), nickel (Ni), arsenic (As), and negative with strontium (Sr) (r) hair scalp concentrations. The negative correlations between right coronary artery disease and magnesium (Mg) and strontium (Sr) concentrations were noted. The possible explanation of different epicardial artery involvement and severity by atherosclerotic processes may lay in their topography and blood rheological characteristics that induce different inflammatory reactions co0factored by specific trace elements. The trace element concentration in the hair scalp may correlate with a particular coronary atherosclerotic involvement, including the severity of lumen reduction. This may indicate the missing link between the pathophysiological processes of atherosclerosis development and its location in coronary arteries.

Abstract Tu010: Matrix metallopeptidase 9 contributes to the beginning of plaque and is a potential biomarker for the early identification of atherosclerosis in asymptomatic patients with diabetes

Aims: To determine the roles of matrix metallopeptidase-9 (MMP9) on human coronary artery smooth muscle cells (HCASMCs) in vitro , early beginning of atherosclerosis in vivo in diabetic mice, and patients with diabetes. Methods: Active hMMP9 ( act-hMMP9) was added to HCASMCs and markers of inflammation were measured. Act-hMMP9 (n=16) or placebo (n=15) was administered to d i abetic KK.Cg- A y /J (KK) mice. Carotid artery inflammation and atherosclerosis measurements were made at 2 and 10 weeks after treatment. An observational study of newly diagnosed drug naïve patients with type 2 diabetes mellitus (T2DM n=234) and healthy matched controls (n=41) was performed and patients had ultrasound of carotid arteries and some had coronary computed tomography angiogram for the assessment of atherosclerosis. Serum MMP9 was measured and its correlation with carotid artery or coronary artery plaques were determined. Results: Act-hMMP9 induced inflammatory response in HCASMCs in vitro , including increased gene and protein expressions of MCP-1, ICAM-1, VCAM-1, and enhanced macrophage adhesion. Exogenous act-hMMP9 increased inflammation and initiated atherosclerosis in KK mice at 2 and 10 weeks: increased vessel wall thickness, lipid accumulation, and Galectin-3+ macrophage infiltration into the carotid arteries. In newly diagnosed T2DM patients, serum MMP9 correlated with carotid artery plaque size with a possible threshold cutoff point. In addition, serum MMP9 correlated with number of mixed plaques and grade of lumen stenosis in coronary arteries of patients with drug naïve T2DM. Conclusions: MMP9 contributes to the initiation of atherosclerosis and may be a potential biomarker for the early identification of atherosclerosis in patients with diabetes

Clinical outcomes of multidrug-resistant tracheobronchial tuberculosis receiving anti-tuberculosis regimens containing bedaquiline or delamanid

The treatment of multidrug-resistant tracheobronchial tuberculosis poses challenges, and research investigating the efficacy of bedaquiline or delamanid as treatment for this condition is limited. This retrospective cohort study was conducted from 2017 to 2021. The study extracted data of patients with multidrug-resistant tracheobronchial tuberculosis from medical records and followed up on prognoses. Participants were divided into three groups: the bedaquiline, delamanid, and control group. Clinical outcomes and the risk factors associated with early culture conversion were analyzed. This study included 101 patients, with 32, 25, and 44 patients in the bedaquiline, delamanid, and control groups respectively. The differences in the treatment success rates among the three groups did not show statistical significance. Both the bedaquiline and delamanid groups had significantly higher culture conversion rates compared to the control after 2 or 6 months of treatment, with significantly shorter median times to culture conversion (bedaquiline group: 2 weeks, delamanid group: 2 weeks, control group: 12 weeks, P < 0.001). Treatment with bedaquiline or delamanid were identified as independent predictors of culture conversion at 2 months (bedaquiline group: aOR = 13.417, 95% CI 4.067–44.260, delamanid group: aOR = 9.333, 95% CI 2.498–34.878) or 6 months (bedaquiline group: aOR = 13.333, 95% CI 3.379–52.610, delamanid group: aOR = 5.000, 95% CI 1.357–18.426) of treatment through multivariable logistic regression analyses. The delamanid group showed better improvement in lumen stenosis compared to bedaquiline. Regimens containing bedaquiline or delamanid may accelerate the culture conversion during the early treatment phase in multidrug-resistant tracheobronchial tuberculosis, and delamanid appears to have the potential to effectively improve airway stenosis.

Efficacy, safety and mechanism of Simiaoyongan decoction in the treatment of carotid atherosclerotic plaque: a randomized, double-blind, placebo-controlled clinical trial protocol

IntroductionChronic inflammation is the major pathological feature of Atherosclerosis(As). Inflammation may accelerate plaque to develop, which is a key factor resulting in the thinning of the fibrous cap and the vulnerable rupture of plaque. Presently, clinical treatments are still lacking. It is necessary to find a safe and effective treatment for As inflammation. Simiaoyongan Decoction (SMYA) has potential anti-inflammatory and plaque protection effects. This protocol aims to evaluate the efficacy, safety, and mechanism of SMYA for patients with carotid atherosclerotic plaque.Methods/designThe assessment of SMYA clinical trial is designed as a randomized, double-blind, placebo-controlled study. The sample size is 86 cases in total, with 43 participants in the intervention group and the control group respectively. The intervention group takes SMYA, while the control group takes SMYA placebo. The medication lasts for 14 days every 10 weeks, with a total of 50 weeks. We will use carotid artery high resolution magnetic resonance imaging (HR-MRI) to measure plaque. The plaque minimum fiber cap thickness (PMFCT) is adopted as the primary outcome. The secondary outcomes include plaque fiber cap volume, volume percentage of fiber cap, lipid-rich necrotic core (LRNC) volume, volume percentage of LRNC, internal bleeding volume of plaque, internal bleeding volume percentage of plaque, plaque calcification volume, volume percentage of plaque calcification, lumen stenosis rate, average and a maximum of vessel wall thickness, vessel wall volume, total vessel wall load, carotid atherosclerosis score, hs-CRP, IL-1β and IL-6, the level of lipid profiles and blood glucose, blood pressure, and body weight.DiscussionWe anticipate that patients with As plaque will be improved from SMYA by inhibiting inflammation to enhance plaque stability. This study analyzes plaque by using HR-MRI to evaluate the clinical efficacy and safety of SMYA. Moreover, we conduct transcriptome analysis, proteomic analysis, and metagenomic analysis of blood and stool of participants to study the mechanism of SMYA against As plaque. This is the first prospective TCM trial to observe and treat As plaque by inhibiting inflammatory reaction directly. If successful, the finding will be valuable in the treatment of As plaque and drug development, especially in the “statin era”.Trial registration numberThis trial is registered on Chinese Clinical Trials.gov with number ChiCTR2000039062 on October 15, 2020 (http://www.chictr.org.cn).

Magnetic resonance imaging combined with serum endolipin and galactagoglobin-3 to diagnose cerebral infarction in the elderly with diabetes mellitus.

Magnetic resonance imaging (MRI) combined with serum endothelin and galactagoglobin-3 (Gal-3) can improve the clinical diagnosis of diabetes mellitus complicated with cerebral infarction. To analyze the clinical value of MRI combined with serum endolipin and Gal-3 for the diagnosis of cerebral infarction in the elderly with diabetes mellitus. One hundred and fifty patients with acute cerebral infarction hospitalized between January 2021 and December 2023 were divided into two groups according to comorbid diabetes mellitus, including 62 and 88 cases in the diabetic and nondiabetic cerebral infarction groups. Serum samples were collected to detect the expression of serum endolipoxins, and Gal-3, and cranial MRI was performed at admission. Differences between the two groups were compared to analyze the diagnostic value of these parameters. Serum endolipin and Gal-3 expression were higher in the diabetic cerebral infarction group (P < 0.05). The arterial wall area, vessel area, normalized wall index, and lumen stenosis rate were higher in the diabetic cerebral infarction group, while the rate of arterial lumen moderate and severe stenosis was 48.39% higher (36.36%, P < 0.05). The percentage of large (29.03%) and multiple infarcts (33.87%) in the diabetic cerebral infarction group was higher (13.64% and 20.45%), and the incidence rate of lacunar infarcts was lower (37.10% vs 65.91%) (P < 0.05). The total incidence of arterial plaque in patients in the diabetic cerebral infarction group was 96.77% higher (69.32%), while the incidence of necrotic lipid core plaque was 58.06% higher (26.14%) (P < 0.05). Receiver operating characteristic curve analysis was performed to assess the diagnosis utility of these techniques. MRI in combination with serum endoglin and Gal-3 had the highest area under the curve, the Yoden index, sensitivity and specificity (P < 0.05). The expression of serum endolipin and Gal-3 in elderly patients with diabetes mellitus with cerebral infarction showed an elevated trend, and the degree of luminal stenosis was severe. MRI predominantly revealed large and multiple infarct foci. This combined index examination can improve the clinical diagnosis of diabetes mellitus combined with cerebral infarction.

A predictive model for ischemic colitis: Integrating clinical and laboratory parameters

AbstractObjectiveWe aimed to develop a predictive model for the clinical diagnosis of ischemic colitis (IC).MethodsClinical data were collected from patients with acute IC lesions who were diagnosed and admitted to Beijing Tsinghua Changgung Hospital from January 2016 to December 2022. These patients were included in the IC case group in this retrospective observational study. The control group comprised patients aged ≥40 years who were diagnosed with abdominal pain during the same period, excluding those with IC. All patients were divided into a training and test sets based on the time window. Least absolute shrinkage and selection operator regression was used to screen risk factors for the occurrence of IC. Logistic stepwise regression (maximum likelihood ratio method) was performed in multifactorial analysis, and a diagnostic prediction model for IC was established using R language. The area under the receiver operating characteristic (ROC) curve (AUC) was examined to assess differentiation using working ROC curves. We used bootstrap resampling (1000 times) for internal validation. Model calibration curves and decision curve analysis (DCA) were also applied.ResultsOur study indicates that constipation, hematochezia, neutrophil counts, and specific abdominal computed tomography (CT) (plain scan) findings, including intestinal wall edema and thickening, intestinal lumen stenosis, and dilation, are independent predictors of IC. The predictive model exhibited high discriminative ability with an AUC of 0.9788 in the training set, and the calibration and DCA curves demonstrated excellent model performance. After validation, the AUC remained robust at 0.9868, underscoring the model's reliability in predicting IC.ConclusionAccording to our model, constipation accompanied by hematochezia necessitates careful consideration of IC. Abdominal CT (plain scan) is an effective diagnostic tool for IC, and it is common for patients to exhibit elevated neutrophil counts. The predictive model, demonstrating high discriminative ability and accuracy, shows promise for practical application in clinical settings, aiding in the early diagnosis and management of IC.