Yersinia infection induces glucose depletion and AMPK-dependent inhibition of pyroptosis in mice.

Nutritional status and pyroptosis are important for host defence against infections. However, the molecular link that integrates nutrient sensing into pyroptosis during microbial infection is unclear. Here, using metabolic profiling, we found that Yersinia pseudotuberculosis infection results in a significant decrease in intracellular glucose levels in macrophages. This leads to activation of the glucose and energy sensor AMPK, which phosphorylates the essential kinase RIPK1 at S321 during caspase-8-mediated pyroptosis. This phosphorylation inhibits RIPK1 activation and thereby restrains pyroptosis. Boosting the AMPK-RIPK1 cascade by glucose deprivation, AMPK agonists, or RIPK1-S321E knockin suppresses pyroptosis, leading to increased susceptibility to Y. pseudotuberculosis infection in mice. Ablation of AMPK in macrophages or glucose supplementation in mice is protective against infection. Thus, we reveal a molecular link between glucose sensing and pyroptosis, and unveil a mechanism by which Y. pseudotuberculosis reduces glucose levels to impact host AMPK activation and limit host pyroptosis to facilitate infection.

C-C Motif Chemokine Ligand 5 (CCL5) as a Predictive Marker for Non-sentinel Lymph Node Presence in Initial-Stage Breast Cancer with 1-2 Affected Sentinel Lymph Nodes.

The objective of our study was to use quantum dots for the purpose of seeing and detecting C-C motif chemokine ligand 5 (CCL5) inside the tissue of sentinel lymph nodes (SLN) and primary tumors. This endeavor aimed to enhance the accuracy of predicting the condition of non-sentinel lymph nodes and provide valuable insights for making informed treatment choices. We analyzed breast cancer patients who underwent sentinel lymph node biopsy followed by axillary lymph node removal due to one or two positive sentinel lymph nodes at the Second People's Hospital of Wuhu, China, between August 2018 and July 2022. Quantum dot technology was employed to visualize and determine CCL5 in the tissue samples from 84 patients. Out of a group diagnosed with breast cancer, 208 underwent sentinel lymph node biopsy. From this pool, 84 tested positive and subsequently underwent axillary lymph node removal. The presence of distinct orange-red fluorescence, linked to quantum dots, was evident in the cellular components of both primary tumors and positive sentinel lymph node tissues. We found a significant relationship between higher levels of SLNCCL5 and advanced tumor growth (P < 0.05). To understand the predictive value of SLN CCL5 related to non-sentinel lymph node status, we utilized the receiver operating characteristic (ROC) method. The area under the curve (AUC) calculated was 0.745 with a cutoff point of 23.285. Multivariate logistic regression was used to understand the effect of tumor dimensions and SLNCCL5 levels on non-sentinel lymph node status in specific patients. Both the size of the tumor and SLNCCL5 levels were found to have a significant impact (P < 0.05). Data suggested that the presence of positive SLNCCL5 might serve as an assessment parameter for anticipating the condition of non-SLN in cases of breast cancer involving T1 or T2 tumors with one or two positive sentinel lymph nodes.

Risk Factors for Implant Failure Following Transcrestal Sinus-Floor Elevation: A Case Report and Literature Review.

Although transcrestal sinus floor elevation (TSFE) is widely used for cases of insufficient residual bone height in the posterior maxilla, few studies have focused on the risk factors of early implant failure associated with TSFE procedures. This study aimed to identify and summarize the possible risk factors of implant failure associated with TSFE to ensure a more predictable implant survival rate using TSFE. We report the treatment of a patient with implant failure following TSFE and discuss this case's possible associated risk factors. A standard implant with a diameter of 4.8 mm and length of 10 mm was used after the TSFE procedure. Implant loosening was suddenly observed six weeks after the initial surgery. Factors that could result in early implant failure included patient-related risk factors, anatomical factors of the operational area, and operation- and implant-related factors. Within the current study's limitations, the graft material particles between the implant surface and socket could be considered a direct risk factor resulting in implant failure. Therefore, more attention should be paid to socket cleaning during the TSFE procedure, and loose particulate grafting materials should be discouraged. Another significant consideration for implant loss is the possibility of fractures in the buccal or palatal cortical plates during the site preparation and implant insertion. Thus, these factors should be studied further and receive more clinical attention.

Proteomic and lipidomic landscape of the infrapatellar fat pad and its clinical significance in knee osteoarthritis.

Osteoarthritis (OA) is a prevalent joint disease that can be exacerbated by lipid metabolism disorders. The intra-articular fat pad (IFP) has emerged as an active participant in the pathological changes of knee OA (KOA). However, the proteomic and lipidomic differences between IFP tissues from KOA and control individuals remain unclear. Samples of IFP were collected from individuals with and without OA (n = 6, n = 6). Subsequently, these samples underwent liquid chromatography/mass spectrometry-based label-free quantitative proteomic and lipidomic analysis to identify differentially expressed proteins (DEPs) and lipid metabolites (DELMs). The DEPs were further subjected to enrichment analysis, and hub DEPs were identified using multiple algorithms. Additionally, an OA diagnostic model was constructed based on the identified hub DEPs or DELMs. Furthermore, CIBERSORT was utilized to investigate the correlation between hub protein expression and immune-related modules in IFP of OA. Our results revealed the presence of 315 DEPs and eight DELMs in IFP of OA patients compared to the control group. Enrichment analysis of DEPs highlighted potential alterations in pathways related to coagulation, complement, fatty acid metabolism, and adipogenesis. The diagnostic model incorporating four hub DEPs (AUC = 0.861) or eight DELMs (AUC = 0.917) exhibited excellent clinical validity for diagnosing OA. Furthermore, the hub DEPs were found to be associated with immune dysfunction in IFP of OA. This study presents a distinct proteomic and lipidomic landscape of IFP between individuals with OA and those without. These findings provide valuable insights into the molecular changes associated with potential mechanisms underlying OA.

Electrochemical Cross-Coupling between N-(4-Hydroxyphenyl)-sulfonamides and 2-Naphthols: Synthesis of 2,2'-Bis(arenol)s.

We herein present an electrochemical method for the dehydrogenative cross-coupling of N-(4-hydroxyphenyl)-sulfonamides and 2-naphthols. This transformation provides a direct and scalable approach to a wide range of C1-symmetric 2,2'-bis(arenol)s with moderate to high yields under mild conditions. Preliminary attempts with the asymmetric variant of this reaction were also performed with ≤55% ee for the synthesis of 2,2'-bis(arenol)s. Control experiments were conducted to propose a plausible mechanism for the reaction.

Dysregulations of amino acid metabolism and lipid metabolism in urine of children and adolescents with major depressive disorder: a case-control study.

RATIONALE: The mechanisms underlying major depressive disorder (MDD) in children and adolescents are unclear. Metabolomics has been utilized to capture metabolic signatures of various psychiatric disorders; however, urinary metabolic profile of MDD in children and adolescents has not been studied. OBJECTIVES: We analyzed urinary metabolites in children and adolescents with MDD to identify potential biomarkers and metabolic signatures. METHODS: Here, liquid chromatography-mass spectrometry was used to profile metabolites in urine samples from 192 subjects, comprising 80 individuals with antidepressant-naïve MDD (AN-MDD), 37 with antidepressant-treated MDD (AT-MDD) and 75 healthy controls (HC). We performed orthogonal partial least squares discriminant analysis to identify differential metabolites and employed logistic regression and receiver operating characteristic analysis to establish a diagnostic panel. RESULTS: In total, 143 and 71 differential metabolites were identified in AN-MDD and AT-MDD, respectively. These were primarily linked to lipid metabolism, molecular transport, and small molecule biochemistry. AN-MDD additionally exhibited dysregulated amino acid metabolism. Compared to HC, a diagnostic panel of seven metabolites displayed area under the receiver operating characteristic curves of 0.792 for AN-MDD, 0.828 for AT-MDD, and 0.799 for all MDD. Furthermore, the urinary metabolic profiles of children and adolescents with MDD significantly differed from those of adult MDD. CONCLUSIONS: Our research suggests dysregulated amino acid metabolism and lipid metabolism in the urine of children and adolescents with MDD, similar to results in plasma metabolomics studies. This contributes to the comprehension of mechanisms underlying children and adolescents with MDD.

A Manganese-Based Nanodriver Coordinates Tumor Prevention and Suppression through STING Activation in Glioblastoma.

Glioblastoma (GBM), the most prevalent and aggressive primary malignant brain tumor, exhibits profound immunosuppression and demonstrates a low response rate to current immunotherapy strategies. Manganese cations (Mn2+) directly activate the cGAS/STING pathway and induce the unique catalytic synthesis of 2'3'-cGAMP to facilitate type I IFN production, thereby enhancing innate immunity. Here, a telodendrimer and Mn2+-based nanodriver (PLHM) with a small size is developed, which effectively target lymph nodes through the blood circulation and exhibit tumor-preventive effects at low doses of Mn2+ (3.7 mg kg-1). On the other hand, the PLHM nanodriver also exhibits apparent antitumor effects in GBM-bearing mice via inducing in vivo innate immune responses. The combination of PLHM with doxorubicin nanoparticles (PLHM-DOX NPs) results in superior inhibition of tumor growth in GBM-bearing mice due to the synergistic potentiation of STING pathway functionality by Mn2+ and the presence of cytoplasmic DNA. These findings demonstrate that PLHM-DOX NPs effectively stimulate innate immunity, promote dendritic cell maturation, and orchestrate cascaded infiltration of CD8 cytotoxic T lymphocytes within glioblastomas characterized by low immunogenicity. These nanodivers chelated with Mn2+ show promising potential for tumor prevention and antitumor effects on glioblastoma by activating the STING pathway.

New Indole Alkaloids from the Fungus Talaromyces assiutensis JTY2.

Three new indole alkaloids, named talatensindoids A-C (1-3), together with two known biogenetically related indole alkaloids tryptamine (4) and L-tryptophan (5) were isolated from the Talaromyces assiutensis JTY2 based on the guidance of OSMAC approach. The structures of these indole alkaloids were determined by comprehensive spectroscopic analyses. The absolute configuration of 3 was confirmed by X-ray crystallographic analysis. Compound 1 represent the rare example of a chlorine-substituted indole alkaloid from natural products. The inhibitory activity of compounds 1-5 against two phytopathogenic fungi and three phytopathogenic bacteria was evaluated. Compound 1 exhibited broad spectrum antibacterial activities.

Relationship between abnormal pelvic floor electromyography and obstetric factors in postpartum women: a cross-sectional study.

OBJECTIVE: To evaluate the surface electromyography (sEMG) of pelvic floor muscles (PFMs), compare between vaginal birth and cesarean section and correlate with maternity and obstetrics characteristics in primiparous 6-8 weeks postpartum. METHODS: PFMs surface electromyography screening data of primiparous postpartum women in our hospital at 6-8 weeks postpartum from 2018 to 2021 were selected and analyzed. The study collected data on delivery activities of 543 postpartum women totally. RESULTS: In general, the abnormal incidence of pelvic floor electromyography in postpartum women mainly occurred in slow muscle (type I fiber) stage and endurance testing stage. Compared to vaginal birth postpartum women, the incidence of abnormal pelvic floor electromyography in cesarean section postpartum women is lower. There were statistical differences in measurement values of pelvic floor electromyography in several different stages between cesarean section and vaginal birth (P < 0.005). Regarding the influence on pelvic floor electromyography, there were more influencing factors on vaginal birth postpartum women including age, height, weight, weight gain during pregnancy, gestational week, and first and second stage of labor than on cesarean section postpartum women whose influencing factors included age, weight gain during pregnancy, and newborn weight. CONCLUSION: Effects on surface electromyography (sEMG) of pelvic floor muscles (PFMs) at 6-8 weeks postpartum differed based on the different modes of delivery. The high-risk obstetric factors closely related to abnormal surface electromyography (sEMG) of pelvic floor muscles (PFMs) were maternal age, height, weight, and second stage of labor.

Prenatal sonographic findings in a case with bilateral Tessier number 7 cleft in first trimester.

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Identifying plasma metabolic characteristics of major depressive disorder, bipolar disorder, and schizophrenia in adolescents.

Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are classified as major mental disorders and together account for the second-highest global disease burden, and half of these patients experience symptom onset in adolescence. Several studies have reported both similar and unique features regarding the risk factors and clinical symptoms of these three disorders. However, it is still unclear whether these disorders have similar or unique metabolic characteristics in adolescents. We conducted a metabolomics analysis of plasma samples from adolescent healthy controls (HCs) and patients with MDD, BD, and SCZ. We identified differentially expressed metabolites between patients and HCs. Based on the differentially expressed metabolites, correlation analysis, metabolic pathway analysis, and potential diagnostic biomarker identification were conducted for disorders and HCs. Our results showed significant changes in plasma metabolism between patients with these mental disorders and HCs; the most distinct changes were observed in SCZ patients. Moreover, the metabolic differences in BD patients shared features with those in both MDD and SCZ, although the BD metabolic profile was closer to that of MDD than to SCZ. Additionally, we identified the metabolites responsible for the similar and unique metabolic characteristics in multiple metabolic pathways. The similar significant differences among the three disorders were found in fatty acid, steroid-hormone, purine, nicotinate, glutamate, tryptophan, arginine, and proline metabolism. Interestingly, we found unique characteristics of significantly altered glycolysis, glycerophospholipid, and sphingolipid metabolism in SCZ; lysine, cysteine, and methionine metabolism in MDD and BD; and phenylalanine, tyrosine, and aspartate metabolism in SCZ and BD. Finally, we identified five panels of potential diagnostic biomarkers for MDD-HC, BD-HC, SCZ-HC, MDD-SCZ, and BD-SCZ comparisons. Our findings suggest that metabolic characteristics in plasma vary across psychiatric disorders and that critical metabolites provide new clues regarding molecular mechanisms in these three psychiatric disorders.

[Microbial Mechanisms of Removal of Phthalic Acid Esters in Purple Soils Revealed Using Metagenomic Analysis].

The removal mechanisms of phthalic acid esters (PAEs) have attracted much attention because of their endocrine-disrupting properties and persistence in environmental media. In order to reveal the removal mechanism of PAEs and involved keystone taxa and functional genes, purple soils were polluted by di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP), respectively, along a gradient of 0, 5, 10, and 20 mg·kg-1 and cultured for 90 days in the dark. The results showed that the degradation dynamics of DBP and DEHP were well-fitted by the first-order kinetic model, and the half-life of DBP and DEHP ranged from 17.0 to 38.2 days. The degradation rate of DBP (5 mg·kg-1) was the fastest, and that of DEHP (20 mg·kg-1) was the slowest. The soil samples of the seventh day and the fifteenth day were analyzed using metagenomic sequencing. NMDS and cluster analysis showed that there was a significant difference between the bacterial community structure of soil samples from the seventh day and the fifteenth day. The relative abundance of Actinobacteria increased from the seventh day to the fifteenth day. The smaller the half-life of DBP or DEHP, the higher the relative abundance of Actinobacteria in the different treatments. In addition, Streptomyces was the dominant genus in all polluted soils. Co-occurrence network analysis elucidated that Pandoraea was a keystone genus of the soil bacterial communities, which could be used to indicate the pollution levels of DBP and DEHP. The results of KEGG annotation demonstrated that Pandoraea was responsible for benzoate degradation, quorum sensing, ABC transporters, and the two-component system and could promote the intercellular communications and the microbial growth and proliferation and maintain the stability of the community structure. Therefore, the degradation rate of DBP and DEHP in purple soils depended on their initial content and their own properties. Actinobacteria played an important role in the PAEs degradation, and Pandoraea played a major part in promoting PAEs degradation and regulating the stability of the structure and function of degrading bacterial communities.

Symptoms experienced after transcatheter arterial chemoembolization in patients with primary liver cancer: A network analysis.

Objective: This study aimed to establish a symptom network for patients with primary liver cancer posttranscatheter arterial chemoembolization (TACE), identifying core and bridge symptoms. The goal is to provide a foundation for precise and comprehensive nursing interventions. Methods: A total of 1207 post-TACE patients were included using a consecutive sampling method. Data collection involved a general information questionnaire, the Anderson Symptom Assessment Scale, and a primary liver cancer-specific symptom module. The symptom network was constructed using the R language. Results: In the overall network, distress exhibited the highest strength (rs = 1.31) and betweenness (rb = 62). Fatigue had the greatest closeness (rc = 0.0043), while nausea and vomiting (r = 0.76 ± 0.02) had the highest marginal weights. Nausea had the highest bridge strength (rbs = 5.263). In the first-time TACE-treated symptom network, sadness (rbs = 5.673) showed the highest bridge strength, whereas in the non-first-time symptom network, fever (rbs = 3.061) had the highest bridge strength. Conclusions: Distress serves as a core symptom, and nausea acts as a bridge symptom after TACE treatment in liver cancer patients. Interventions targeting bridge symptoms should be tailored based on the number of treatments, enhancing the quality of symptom management.

Analysis of health service utilization and influencing factors due to COVID-19 in Beijing: a large cross-sectional survey.

BACKGROUND: In the wake of China's relaxed zero-COVID policy, there was a surge in coronavirus disease 2019 (COVID-19) infections. This study aimed to examine the infection status and health service utilization among Beijing residents during a widespread outbreak, and to explore the factors that affected utilization of health services due to COVID-19. METHODS: A cross-sectional survey was conducted among Beijing residents from 13 January to 13 February 2023, collecting information on socio-demographic characteristics, health behaviours, COVID-19 infection status, utilization of health services and depressive symptoms. Multivariate Tobit regression was used for data analysis. RESULTS: Among the 53 924 participants, 14.7% were older than 60 years, 63.7% were female and 84.8% were married. In total, 44 992 of the 53 924 individuals surveyed (83.4%) contracted COVID-19 during 2020-2023, and 25.2% (13 587) sought corresponding health services. The majority of individuals (85.6%) chose in-person healthcare, while 14.4% chose internet-based healthcare. Among those who chose in-person healthcare, 58.6% preferred primary healthcare institutions and 41.5% were very satisfied with the treatment. Factors affecting health service utilization include being female (ß = -0.15, P < 0.001), older than 60 years (ß = 0.23, P < 0.01), non-healthcare workers (ß = -0.60, P < 0.001), rich self-rated income level (ß = 0.59, P < 0.001), having underlying disease (ß = 0.51, P < 0.001), living alone (ß = -0.19, P < 0.05), depressive symptoms (ß = 0.06, P < 0.001) and healthy lifestyle habits, as well as longer infection duration, higher infection numbers and severe symptoms. CONCLUSION: As COVID-19 is becoming more frequent and less severe, providing safe and accessible healthcare remains critical. Vulnerable groups such as the elderly and those with underlying conditions need reliable health service. Prioritizing primary healthcare resources and online medical services have played a vital role in enhancing resource utilization efficiency.

Bioactive 5/5/5/6 Four-Ring System Iridoids from Plumeria alba L.

Two rare 5/5/5/6 four-ring system iridoids, allamancins A and B (1 and 2) together with one known biogenetically related iridoid derivative, 3-O-methyallamancin (3) were isolated from the flowers of Plumeria alba L. The structures of these iridoid derivatives were determined by comprehensive spectroscopic analyses. The absolute configuration of 1 was confirmed by X-ray crystallographic analysis. The inhibitory activities of compounds 1-3 against nitric oxide (NO) production induced and three cancer cell lines were evaluated in vitro. Compounds 1 and 3 showed inhibitory activities on NO production with IC50 values of 18.3±0.12 and 22.1±0.14 µM, respectively. Compounds 1-3 showed moderate inhibitory activities against cancer cell lines of A549, Hela and MCF-7.

Symptom networks in older adults with cancer: A network analysis.

INTRODUCTION: Due to aging, older adults with cancer (OAC) may be confronted with a complex interplay of multiple age-related issues; coupled with receiving cancer treatment, OAC may experience multiple concurrent symptoms that require the identification of the core symptom for effective management. Constructing symptom networks will help in the identification of core symptoms and help achieve personalized and precise interventions. Currently, few studies have used symptom networks to identify core symptoms in OAC. Our objectives were to construct symptom networks of OAC, explore the core symptoms, and compare the differences in symptom networks among various subgroups. MATERIALS AND METHODS: Secondary analysis was performed using data from 485 OAC collected in 2021 from a cross-sectional survey named the Shanghai CANcer Survivor (SCANS) Report. The MD Anderson Symptom Inventory (MDASI) was used to assess the incidence and severity of cancer-related symptoms. We used the R package to construct symptom networks and identify the centrality indices. The network comparison test was used to compare network differences among the subgroups. RESULTS: The most common and severe symptoms reported were fatigue, disturbed sleep, and difficulty remembering. The network density was 0.718. Vomiting (rs = 1.81, rb = 2.13), fatigue (rs = 1.54, rb = 1.93), and sadness (rs = 0.81, rb = 0.69) showed the highest strength values, which suggested that these symptoms were more likely to co-occur with other symptoms. The network comparison tests showed significant differences in symptom network density between the subgroups categorized as survival "< 5 years" and survival "≥ 5 years" (p = 0.002), as well as between the those with comorbidities and those without comorbidities (p = 0.037). DISCUSSION: Our study identified symptom networks in 485 OAC. Vomiting, fatigue, and sadness were important symptoms in the symptom networks of OAC. The symptom networks differed among populations with different survival durations and comorbidities. Our network analysis provides a reference for future targeted symptom management and interventions in OAC. In the future, conducting dynamic research on symptom networks will be crucial to explore interaction mechanisms and change trends between symptoms.

Risk perceptions of COVID-19 in Beijing: a cross-sectional study.

Background: The Chinese government has ended the "dynamic zero-COVID" policy, and residents are now living together with the SARS-CoV-2 virus. Only a limited number of studies have investigated the specific content and structure of COVID-19-related risk perceptions, as well as their underlying determinants. This study measured the residents' risk perception of COVID-19 and analyzed the predictors of RP. Methods: We conducted a comprehensive questionnaire-based survey among residents mostly in Beijing, using a specially designed scale consisting of 11 items to accurately measure COVID-19 risk perceptions. We then utilized multiple linear regression analysis to investigate the factors associated with risk perceptions. Results: A total of 60,039 residents participated in the survey. Our study reveals that COVID-19-related worries are significantly influenced by other dimensions of RP (p < 0.001), except for perceived society's control of the epidemic. Several experiential and socio-demographic factors, including gender, educational level, and infectious experience, are notably correlated with all dimensions of risk perceptions of COVID-19. Conclusion: This study evaluates the specific content and structure of COVID-19-related risk perceptions, as well as their determinants. It is essential to understand the risk perceptions and health-protective behaviors of residents with diverse educational levels, incomes, and medical histories.

Evaluation of nocturnal apnea and airflow limitation as indicators for cognitive dysfunction in patients with chronic obstructive pulmonary disease/obstructive sleep apnea hypopnea syndrome overlap syndrome.

OBJECTIVE: The aim of this study is to investigate how much intermittent hypoxemia and airflow limitation contribute to cognitive impairment in overlap syndrome (OS), which is the coexistence of two common diseases, obstructive sleep apnea hypopnea syndrome (OSAHS) and chronic obstructive pulmonary disease (COPD). METHODS: We conducted a cross-sectional study of patients with OSAHS, COPD or OS, compared with normal controls, to determine the association between sleep apnea/pulmonary function-related indicators and cognitive dysfunction in individuals with OSAHS, COPD or OS. RESULTS: A total of 157 participants were recruited. Both OSAHS and OS presented lower adjusted Montreal cognitive assessment (MoCA) scores compared with COPD group. In addition, the MoCA score was significantly lower in COPD group compared with control group. The incidence of cognitive impairment was 57.4% in OSAHS group, and 78% in OS group, which were significantly higher than COPD group (29%) and control group (8.8%). Furthermore, a broader range of cognitive domains were affected in OS group compared with OSAHS group. Elevated levels of oxygen desaturation index (ODI) and/or apnea hypopnea index (AHI) were positively correlated with increased Epworth sleeping scale (ESS) in OSAHS and OS. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and peak expiratory flow (PEF) were positively correlated with cognitive scores in OSAHS but not in OS. Serum level of hypoxia-inducible factor-1α (HIF-1α) was significantly higher in OS. Logistic regression identified ODI as an independent risk factor for cognitive impairment in OS, while severity of snoring and PEF were independent risk factors in OSAHS. DISCUSSION: This study revealed significant cognitive impairment in OS, OSAHS and COPD. Sleep-related indicators are warranted in OS patients for detection, differentiation and grading of cognitive impairment, whereas pulmonary functions are warranted in OSAHS patients for detection and early intervention of cognitive impairment.

No evidence of coronary plaque stabilization by allopurinol in patients with acute coronary syndrome.

BACKGROUND: Allopurinol, a xanthine inhibitor that lowers uric acid concentration, has been proven to reduce inflammation and oxidative stress in patients with cardiovascular disease. However, it is unknown whether these beneficial effects translate into favorable plaque modification in acute coronary syndromes (ACS). This study aimed to investigate whether allopurinol could improve coronary plaque stabilization using coronary computed tomography angiography (CCTA). METHODS: This was a prospective, single-center, randomized, double-blind clinical trial began in March 2019. A total of 162 ACS patients aged 18-80 years with a blood level of high-sensitivity C-reactive protein (hsCRP) â€‹> â€‹2 â€‹mg/L were included. The subjects were randomly assigned in a 1:1 ratio to receive either allopurinol sustained-release capsules (at a dose of 0.25 â€‹g once daily) or placebo for 12 months. The plaque analysis was performed at CCTA. The primary efficacy endpoint was the change in low-attenuation plaque volume (LAPV) from baseline to the 12-month follow-up. RESULTS: Among 162 patients, 54 in allopurinol group and 51 in placebo group completed the study. The median follow-up duration was 14 months in both groups. Compared with placebo, allopurinol therapy did not significantly alter LAPV (-13.4 â€‹± â€‹3.7 â€‹% vs. -17.8 â€‹± â€‹3.6 â€‹%, p â€‹= â€‹0.390), intermediate attenuation plaque volume (-16.1 â€‹± â€‹3.0 â€‹% vs. -16.2 â€‹± â€‹2.9 â€‹%, p â€‹= â€‹0.992), dense calcified plaque volume (12.2 â€‹± â€‹13.7 â€‹% vs. 9.7 â€‹± â€‹13.0 â€‹%, p â€‹= â€‹0.894), total atheroma volume (-15.2 â€‹± â€‹3.2 â€‹% vs. -16.4 â€‹± â€‹3.1 â€‹%, p â€‹= â€‹0.785), remodeling index (2.0 â€‹± â€‹3.9 â€‹% vs. 5.4 â€‹± â€‹3.8 â€‹%, p â€‹= â€‹0.536) or hsCRP levels (-73.6 [-91.6-17.9] % vs. -81.2 [-95.4-47.7] %, p â€‹= â€‹0.286). CONCLUSIONS: Our findings suggest that allopurinol does not improve atherosclerotic plaque stability or inflammation in ACS.