Machine learning models for predicting the risk factor of carotid plaque in cardiovascular disease.

Introduction: Cardiovascular disease (CVD) is a group of diseases involving the heart or blood vessels and represents a leading cause of death and disability worldwide. Carotid plaque is an important risk factor for CVD that can reflect the severity of atherosclerosis. Accordingly, developing a prediction model for carotid plaque formation is essential to assist in the early prevention and management of CVD. Methods: In this study, eight machine learning algorithms were established, and their performance in predicting carotid plaque risk was compared. Physical examination data were collected from 4,659 patients and used for model training and validation. The eight predictive models based on machine learning algorithms were optimized using the above dataset and 10-fold cross-validation. The Shapley Additive Explanations (SHAP) tool was used to compute and visualize feature importance. Then, the performance of the models was evaluated according to the area under the receiver operating characteristic curve (AUC), feature importance, accuracy and specificity. Results: The experimental results indicated that the XGBoost algorithm outperformed the other machine learning algorithms, with an AUC, accuracy and specificity of 0.808, 0.749 and 0.762, respectively. Moreover, age, smoke, alcohol drink and BMI were the top four predictors of carotid plaque formation. It is feasible to predict carotid plaque risk using machine learning algorithms. Conclusions: This study indicates that our models can be applied to routine chronic disease management procedures to enable more preemptive, broad-based screening for carotid plaque and improve the prognosis of CVD patients.

SARS-CoV-2 N protein enhances the anti-apoptotic activity of MCL-1 to promote viral replication.

Viral infection in respiratory tract usually leads to cell death, impairing respiratory function to cause severe disease. However, the diversity of clinical manifestations of SARS-CoV-2 infection increases the complexity and difficulty of viral infection prevention, and especially the high-frequency asymptomatic infection increases the risk of virus transmission. Studying how SARS-CoV-2 affects apoptotic pathway may help to understand the pathological process of its infection. Here, we uncovered SARS-CoV-2 imployed a distinct anti-apoptotic mechanism via its N protein. We found SARS-CoV-2 virus-like particles (trVLP) suppressed cell apoptosis, but the trVLP lacking N protein didn't. Further study verified that N protein repressed cell apoptosis in cultured cells, human lung organoids and mice. Mechanistically, N protein specifically interacted with anti-apoptotic protein MCL-1, and recruited a deubiquitinating enzyme USP15 to remove the K63-linked ubiquitination of MCL-1, which stabilized this protein and promoted it to hijack Bak in mitochondria. Importantly, N protein promoted the replications of IAV, DENV and ZIKV, and exacerbated death of IAV-infected mice, all of which could be blocked by a MCL-1 specific inhibitor, S63845. Altogether, we identifed a distinct anti-apoptotic function of the N protein, through which it promoted viral replication. These may explain how SARS-CoV-2 effectively replicates in asymptomatic individuals without cuasing respiratory dysfunction, and indicate a risk of enhanced coinfection with other viruses. We anticipate that abrogating the N/MCL-1-dominated apoptosis repression is conducive to the treatments of SARS-CoV-2 infection as well as coinfections with other viruses.

Comparison of the Efficacy and Safety of Temporary Spinal Cord Stimulation versus Pulsed Radiofrequency for Postherpetic Neuralgia: A Prospective Randomized Controlled Trial.

Objectives: The objective of this study is to compare the safety and effectiveness of the temporary spinal cord stimulation (SCS) versus pulsed radiofrequency (PRF) in treating postherpetic neuralgia (PHN). Methods: From September 1, 2019, to May 30, 2020, 44 PHN patients admitted to the Pain Department of the Foshan First People's Hospital, China were enrolled in this study. The patients were randomly assigned to SCS and PRF groups in a ratio of 1 : 1 and were given respective therapy for 8 days. Rash, in all patients, was located in the trunk and extremities of the spinal nerve (C4-L5), and the pain intensity was greater than or equal to 7 points on the VAS scale. Subsequently, we evaluated the visual analogue scale (VAS), efficiency rate (ER), complete remission rate (CRR), daily sleep interference score (SIS), patient health questionnaire (PHQ-9), generalized anxiety disorder assessment (GAD-7), bodily pain (BP), and physical function (PF) sections of the 36-item short-form health survey (SF-36) at the following time points: presurgery, as well as 1 week, 1 month, 3 months, and 6 months postsurgery. Results: The final analysis was performed on 40 patients (n = 20 SCS cohort, and n = 20 PRF cohort). Both cohorts exhibited comparable baseline values (P > 0 : 05). Particularly, they were similar in age, sex, pain duration, involved dermatome, and comorbidity. Among the variables that demonstrated marked improvements from presurgical data to 1 week postsurgery were VAS, ER, CRR, SIS, PHQ-9, GAD-7, as well as BP and PF of the SF-36 in both cohorts. In addition, this improvement persisted for 6 months. There was no complication related to surgery in any of our patients. Conclusion: Based on our analysis, SCS exhibited better efficacy and safety than PRF. This study was prospectively registered in the Chinese Clinical Trial Registry (ChiCTR2100050647).

Reduction of SIRT1 Mediates Monosodium Iodoacetate-Induced Osteoarthritic Pain by Upregulating p53 Expression in Rats.

BACKGROUND: Clinically, chronic pain is the most common and disabling symptom of osteoarthritis (OA). OA pain is associated with OA lesion of the knee and the plastic changes in the peripheral and central nervous systems. However, the central mechanisms involved at the spinal cord level are not fully understood. OBJECTIVES: The aim of this study was to identify the mechanism underlying the role of spinal cord Sirtuin 1 (SIRT1) in OA pain induced by intraarticular injection of monosodium iodoacetate (MIA) in rats. STUDY DESIGN: Controlled animal study. METHODS: MIA was injected intraarticularly into the rat knee joint for the induction of OA. The OA lesion of the knee was assessed by histopathological examination. The mechanical allodynia were measured over 21 days post-injection by von Frey filaments. The messenger RNA and protein levels of SIRT1 and p53 were determined by real-time quantitative polymerase chain reaction and western blotting, respectively. Involvement of SIRT1-mediated p53 expression in the development of MIA-persistent pain was studied using intrathecal (i.t.) injection of the SIRT1-activating molecule resveratrol and intraperitoneal (i.p.) injection of the p53 inhibitor pifithrin-mu (PTF-µ). RESULTS: MIA induced mechanical allodynia, decreased the expression of SIRT1, and upregulated the expression of p53 in the spinal dorsal horn. Consecutive i.t. injection of resveratrol or i.p. injection of PTF-µ alleviated the MIA-induced mechanical allodynia. Upregulation of dorsal horn SIRT1 expression by i.t. injection of resveratrol also inhibited the increase of dorsal horn p53 induced by MIA. Moreover, silencing of dorsal horn SIRT1 expression by i.t. administration of small interfering RNA SIRT1 into normal rats induced the mechanical allodynia and upregulation of p53 expression in the dorsal horn. LIMITATIONS: More underlying mechanism(s) of the role of p53 signaling pathway in OA pain need to be explored in future research. CONCLUSIONS: These findings suggest that the reduction of dorsal horn SIRT1 mediated upregulation of p53 expression, which plays a critical role in persistent pain induced by OA. The i.t. drug delivery treatments targeting the spinal cord SIRT1/p53 pathway might be novel therapeutic options for OA-induced persistent pain.