Causal Association of Golgi Protein 73 With Coronary Artery Disease: Evidence from Proteomics and Mendelian Randomization.

Background: Identification of the unknown pathogenic factor driving atherosclerosis not only enhances the development of disease biomarkers but also facilitates the discovery of new therapeutic targets, thus contributing to the improved management of coronary artery disease (CAD). We aimed to identify causative protein biomarkers in CAD etiology based on proteomics and 2-sample Mendelian randomization (MR) design. Methods: Serum samples from 33 first-onset CAD patients and 31 non-CAD controls were collected and detected using protein array. Differentially expressed analyses were used to identify candidate proteins for causal inference. We used 2-sample MR to detect the causal associations between the candidate proteins and CAD. Network MR was performed to explore whether metabolic risk factors for CAD mediated the risk of identified protein. Vascular expression of candidate protein in situ was also detected. Results: Among the differentially expressed proteins identified utilizing proteomics, we found that circulating Golgi protein 73 (GP73) was causally associated with incident CAD and other atherosclerotic events sharing similar etiology. Network MR approach showed low-density lipoprotein cholesterol and glycated hemoglobin serve as mediators in the causal pathway, transmitting 42.1% and 8.7% effects from GP73 to CAD, respectively. Apart from the circulating form of GP73, both mouse model and human specimens imply that vascular GP73 expression was also upregulated in atherosclerotic lesions and concomitant with markers of macrophage and phenotypic switching of vascular smooth muscle cells (VSMCs). Conclusions: Our study supported GP73 as a biomarker and causative for CAD. GP73 may involve in CAD pathogenesis mainly via dyslipidemia and hyperglycemia, which may enrich the etiological information and suggest future research direction on CAD.

GP73 enhances the ox-LDL-induced inflammatory response in THP-1 derived macrophages via affecting NLRP3 inflammasome signaling.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease with its molecular basis incompletely understood. Here, we determined whether the Golgi phosphoprotein 73 (GP73), a novel protein highly related to inflammation and disrupted lipid metabolism, was involved in the development of atherosclerosis. METHODS: Public microarray databases of human vascular samples were analyzed for expression patterns. Apolipoprotein-E-gene-deficient (ApoE-/-) mice (8-week-old) were randomly assigned to either a chow diet group or a high-fat diet group. The levels of serum GP73, lipid profiles and key inflammatory cytokines were determined by ELISA. The aortic root plaque was isolated and used for by Oil Red O staining. PMA-differentiated THP-1 macrophages were transfected with GP73 small interfering RNA (siRNA) or infected with adenovirus expressing GP73, and then stimulated with oxidized low density lipoprotein (ox-LDL). The expressions of pro-inflammatory cytokines and signal pathway key targets were determined by ELISA kit and Western blot respectively. In addition, ichloro-dihydro-fluorescein diacetate (DCFH-DA) was used to measure the intracellular ROS levels. RESULTS: The expressions of GP73 and NLRP3 were substantially upregulated in human atherosclerotic lesions. There were significant linear correlations between GP73 and inflammatory cytokines expressions. High-fat diet-induced atherosclerosis and increased levels of plasma inflammatory mediators (IL-1ß, IL-18, and TNF-α) were observed in ApoE-/- mice. Besides, the expressions of GP73 in the aorta and serum were significantly upregulated and positively correlated with the NLRP3 expression. In the THP-1 derived macrophages, ox-LDL treatment upregulated the expressions of GP73 and NLRP3 proteins and activated the inflammatory responses in a concentration-dependent and time-dependent manner. Silencing of GP73 attenuated the inflammatory response and rescued the decreased migration induced by ox-LDL, inhibiting the NLRP3 inflammasome signaling and the ROS and p-NF-κB activation. CONCLUSIONS: We demonstrated that GP73 promoted the ox-LDL-induced inflammation in macrophages by affecting the NF-κB/NLRP3 inflammasome signaling, and may play a role in atherosclerosis.

Virtual-reality-based social cognition and interaction training for patients with schizophrenia: A preliminary efficacy study.

Background: Social cognition and interaction training (SCIT) is a psychosocial intervention program for patients with psychosis, designed to improve their social functioning by improving social cognition. Although the feasibility and efficacy of SCIT have been verified, patients with schizophrenia tend to suffer from motivational deficits and low treatment adherence. It has been suggested that using virtual reality (VR) technology might be effective in addressing these issues. In this study, we aimed to develop a VR-based SCIT and compare its efficacy with that of traditional SCIT. Materials and methods: We developed a novel VR-based social cognition and interaction training (VR-SCIT) that combines traditional SCIT (TR-SCIT) intervention with VR technology. Participants were randomly assigned in a 1:1:1 ratio to the VR-SCIT (n = 28), TR-SCIT (n = 30), or waiting-list groups (n = 29). All treatments were combined with treatment-as-usual. Assessments of social cognition (i.e., Chinese version of Face-Affective Identification Task, Chinese version of Social Cognition Screening Questionnaire) and social functioning (i.e., Chinese version of Personal and Social Performance Scale) were administered from baseline to post-intervention. Results: Patients receiving VR-SCIT and TR-SCIT showed a significantly greater improvement on the assessments of emotion perception (Cohen's d was 1.66, 0.55, and 0.10 for VR-SCIT, TR-SCIT, and Waiting-list, respectively), hostile attributional bias (Cohen's d was 0.48, 0.44, and 0.05 for VR-SCIT, TR-SCIT, and Waiting-list, respectively), metacognition (Cohen's d was 1.66, 0.76, and 0.06 for VR-SCIT, TR-SCIT, and waiting-list, respectively), and social functioning (Cohen's d was 1.09, 0.90, and 0.20 for VR-SCIT, TR-SCIT, and waiting-list, respectively) from baseline to post-intervention, compared to those in waiting-list group. Additionally, VR-SCIT showed an advantage over TR-SCIT in improving emotion perception and metacognition with higher treatment compliance. Conclusion: These preliminary findings indicate that VR-SCIT is a feasible and promising method for improving social cognition and social functioning in patients with schizophrenia.

A systematic review of guidelines for dual antiplatelet therapy in coronary artery bypass graft.

BACKGROUND: In most situations, many patients undergoing coronary artery bypass graft (CABG) are on dual antiplatelet therapy (DAPT), which is also required after CABG. The adjustment of antiplatelet strategy remains controversial. In this study, we systematically review current guidelines, seeking consensus and controversies to facilitate clinical practice. METHODS AND RESULTS: Guidelines are searched in PubMed, Embase, ECRI Guidelines Trust and websites of guidelines organizations and professional society. Guidelines with recommendations of DAPT for patients undergo CABG are included. Two reviewers appraised guidelines with the Appraisal of Guidelines for Research and Evaluation II (AGREE II). Relevant recommendations are extracted and summarized. A total of 14 guidelines meeting inclusion criteria are selected, with average AGREE II scores from 44% to 86%. Most guidelines score high in domains other than 'applicability'. Many guidelines are not detailed enough in reporting considerations behind recommendations. Current guidelines are consistent on the management of antiplatelet strategy before elective CABG and using DAPT after surgery for preventing graft vessel occlusion. Evidence is still lacking in urgent CABG and resumption of the previous DAPT after surgery. CONCLUSIONS: Current guidelines on DAPT in CABG are generally satisfying. Suspending P2Y12 inhibitors while aspirin continued before elective CABG is recommended, as well as 12 months of DAPT following CABG. More evidence is needed to guide antiplatelet therapy in urgent CABG and to prove the benefits of resuming previous DAPT.

A virtual reality counterconditioning procedure to reduce methamphetamine cue-induced craving.

The present work developed a virtual reality (VR) counterconditioning procedure (VRCP), and investigated its efficacy in treatment of cue-induced craving in individuals with methamphetamine (METH) dependence. In study 1, thirty-one patients diagnosed with METH dependence received VRCP, while twenty-nine METH-dependent patients in waiting-list group did not. In study 2, the VRCP was computerized as a VR treatment system. Six-hundred and twelve abstinent individuals with a history of METH dependence received the computerized VRCP, while two-hundred seventy-six abstinent individuals with a history of METH dependence in waiting-list group did not. Patients with METH dependence who received VRCP showed a significantly larger decrease on the score of METH-craving and METH-liking from baseline to follow-up assessments, compared to those who did not received VRCP. Participants received VRCP showed a significantly larger decrease in HRV indexes on time domain and non-linear domain from baseline to follow-up assessments during exposure to VR cues, compared to those in waiting-list group. These findings indicate that the counterconditioning procedure under VR environment may be a useful strategy in suppressing cue-induced reactivity for patients with METH dependence.

[Study of Fermi resonance characteristic of CS2 in THF].

In the present paper, an innovative experiment was done. The authors measured the Raman spectra of CS2 mixed with THF at different volume fractions. According to the J. F. Bertran theory, we analyzed the changing regularity of v1-2v2 Fermi resonance along with the different concentration. It was shown that the characteristic parameters of Fermi resonance in solution, such as spectra intensity, frequency space, coupling coefficient and anharmonic constant, will make changes along with solution concentration variation. Because of the existing of solvent effects, the spectra intensity decreases gradually, and the coupling coefficient increases gradually. The explanation of such changes is that the vibration spectra are affected not only by scattering coefficient, but also by more weak hydrogen bond's formation. In addition, the asymmetric frequency shift of the Raman spectra was also found in the paper. The fundamental frequency v1 basically has no shifts, but the overtone frequency 2v2 moves towards the high wave number gradually, which is inconsistent with the theory of symmetrical movement. According to the study of molecular microcosmic action, the formation and mechanism of the weak hydrogen bond can preferably explain the above phenomenon. The research has a major influence on the further study of solvent effects in Fermi resonance. And the paper will also provide certain reference value for the study of molecule vibration spectra in solution.