Combined vaccines against angiotensin II receptor type 1 and alpha 1D-adrenergic receptor for hypertension.

PURPOSE: Compared with monotherapy, combination therapy with multiple antihypertensive drugs has demonstrated superior efficacy in the management of hypertension. The aim of this study was to explore the efficacy of multitarget combined vaccines in achieving simultaneous antihypertensive and target organ protection effects. METHODS: Our team has developed ATRQß-001 and ADRQß-004 vaccines targeting Ang II type 1 receptor (AT1R) and α1D-adrenergic receptor (α1D-AR), respectively. In NG-nitroarginine methyl ester (l-NAME) + abilities spontaneously hypertensive rats (SHRs) model, SHRs were simultaneously inoculated with ATRQß-001 and ADRQß-004 vaccines. Histological and biochemical analyses were performed to evaluate the antihypertensive effects and target organ protection of the ATRQß-001 and ADRQß-004 combined vaccines in comparison with those of the single vaccine. RESULTS: Both ATRQß-001 and ADRQß-004 vaccines induced robust antibody production, resulting in persistent high antibody titers in rats. Notably, the combined administration of both vaccines significantly decreased SBP in SHRs compared with treatment with a single vaccine, both before and after l-NAME administration. Furthermore, the combined vaccine regimen demonstrated superior efficacy in protecting against vascular remodeling, myocardial hypertrophy and fibrosis, and kidney injury in SHRs. Mechanistically, the combined vaccines exhibited significantly downregulated the expression of angiotensin II type 1 receptor (AT1R) and α1D-adrenergic receptor (α1D-AR). Importantly, no apparent immune-related adverse effects were observed in animals immunized with the combined vaccines. CONCLUSION: Preliminary findings from this investigation suggest that co-administration of the novel ATRQß-001 and ADRQß-004 vaccines holds potential as a groundbreaking therapeutic strategy for managing hypertension.Graphical abstract: http://links.lww.com/HJH/C436.

Associations between somatic symptoms and remission of major depressive disorder: A longitudinal study in China.

Previous studies have documented negative associations between somatic symptoms and remission of major depressive disorder (MDD). However, the correlations of specific somatic symptoms with remission remain uncertain. We aimed to explore the associations between specific somatic symptoms and remission focusing on sex differences among patients with MDD. We used data from patients with MDD in the Depression Cohort in China. At baseline, total somatic symptoms were evaluated using the 28-item Somatic Symptoms Inventory and were categorized into pain, autonomic, energy, and central nervous system (CNS) symptoms. To measure remission of MDD, depressive symptoms were evaluated using the Patient Health Questionnaire-9 after 3 months of treatment. We ultimately included 634 patients. Compared with quartile 1 of total somatic symptom scores, the full-adjusted ORs (95% CIs) for remission from quartile 2 to quartile 4 were 0.52 (0.30, 0.90), 0.44 (0.23, 0.83), and 0.36 (0.17, 0.75), respectively (P-value for trend = 0.005). The restricted cubic spline showed no non-linear associations between total somatic symptoms with remission (P-value for non-linear = 0.238). Pain, autonomic, and CNS symptoms showed similar results. Sex-stratified analysis showed that total somatic symptoms, pain symptoms, and autonomic symptoms were negatively correlated with remission in females, whereas CNS symptoms were negatively associated with remission in males. Our findings indicate that specific somatic symptoms exert differential effects on remission of MDD. Therapeutic interventions that target pain, autonomic, and CNS symptoms may increase the probability of remission. Furthermore, interventions for somatic symptoms should be tailored by sex, and females deserve more attention.

Mortality in patients admitted to hospital with heart failure in China: a nationwide Cardiovascular Association Database-Heart Failure Centre Registry cohort study.

BACKGROUND: China has the largest burden of heart failure worldwide. However, large-scale studies on heart failure mortality are scarce. We aimed to investigate mortality and identify risk factors for mortality among patients with heart failure in China. METHODS: This prospective cohort study used data from the China Cardiovascular Association (CCA) Database-Heart Failure Centre Registry, which were linked to the National Mortality Registration Information Management System by the Chinese Centre for Disease Control and Prevention. We included patients enrolled from Jan 1, 2017, to Dec 31, 2021, across 572 CCA Database-Heart Failure Centre certified hospitals in 31 provinces of mainland China. Eligible patients were aged 18 years or older (younger than 100 years) with a principal discharge diagnosis of heart failure based on Chinese heart failure guidelines. All-cause mortality at 30 days, 1 year, and 3 years for patients with heart failure were calculated and the causes of death were recorded. Multivariable analysis was used to analyse factors associated with all-cause mortality and cardiovascular mortality. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2200066305. FINDINGS: Of the 327 477 patients in the registry, 230 637 eligible adults with heart failure were included in our analyses. Participant mean age was 69·3 years (SD 13·2), 94 693 (41·1%) participants were female, and 135 944 (58·9%) were male. The median follow-up time was 531 days (IQR 251-883). Post-discharge all-cause mortality of patients with heart failure at 30 days was 2·4% (95% CI 2·3-2·5), at 1 year was 13·7% (13·5-13·9), and at 3 years was 28·2% (27·7-28·6). Cardiovascular death accounted for 32 906 (71·5%) of 46 006 all-cause deaths. Patients with heart failure with reduced ejection fraction had the highest all-cause mortality. A lower guideline adherence score was independently associated with the increase of all-cause and cardiovascular mortality. INTERPRETATION: In China, mortality for patients with heart failure is still high, especially in patients with reduced ejection fraction. Our findings suggest that guideline-directed medical therapy needs to be improved. FUNDING: National High Level Hospital Clinical Research Funding, the Capital's Funds for Health Improvement and Research, and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

The novel vaccines targeting interleukin-1 receptor type I.

OBJECTIVE: There is mounting evidence indicating that atherosclerosis represents a persistent inflammatory process, characterized by the presence of inflammation at various stages of the disease. Interleukin-1 (IL-1) precisely triggers inflammatory signaling pathways by binding to interleukin-1 receptor type I (IL-1R1). Inhibition of this signaling pathway contributes to the prevention of atherosclerosis and myocardial infarction. The objective of this research is to develop therapeutic vaccines targeting IL-1R1 as a preventive measure against atherosclerosis and myocardial infarction. METHODS: ILRQß-007 and ILRQß-008 vaccines were screened, prepared and then used to immunize high-fat-diet fed ApoE-/- mice and C57BL/6J mice following myocardial infarction. Progression of atherosclerosis in ApoE-/- mice was assessed primarily by oil-red staining of the entire aorta and aortic root, as well as by detecting the extent of macrophage infiltration. The post-infarction cardiac function in C57BL/6J mice were evaluated using cardiac ultrasound and histological staining. RESULTS: ILRQß-007 and ILRQß-008 vaccines stimulated animals to produce high titers of antibodies that effectively inhibited the binding of interleukin-1ß and interleukin-1α to IL-1R1. Both vaccines effectively reduced atherosclerotic plaque area, promoted plaque stabilization, decreased macrophage infiltration in plaques and influenced macrophage polarization, as well as decreasing levels of inflammatory factors in the aorta, serum, and ependymal fat in ApoE-/- mice. Furthermore, these vaccines dramatically improved cardiac function and macrophage infiltration in C57BL/6J mice following myocardial infarction. Notably, no significant immune-mediated damage was observed in immunized animals. CONCLUSION: The vaccines targeting the IL-1R1 would be a novel and promising treatment for the atherosclerosis and myocardial infarction.

Identifying novel proteins for suicide attempt by integrating proteomes from brain and blood with genome-wide association data.

Genome-wide association studies (GWASs) have identified risk loci for suicide attempt (SA), but deciphering how they confer risk for SA remains largely unknown. This study aims to identify the key proteins and gain insights into SA pathogenesis. We integrated data from the brain proteome (N = 376) and blood proteome (N = 35,559) and combined it with the largest SA GWAS summary statistics to date (N = 518,612). A comprehensive set of methods was employed, including Mendelian randomization (MR), Steiger filtering, Bayesian colocalization, proteome­wide association studies (PWAS), transcript-levels, cell-type specificity, correlation, and protein-protein interaction (PPI) network analysis. Validation was performed using other protein datasets and the SA dataset from FinnGen study. We identified ten proteins (GLRX5, GMPPB, B3GALTL, FUCA2, TTLL12, ADCK1, MMAA, HIBADH, ACP1, DOC2A) associated with SA in brain proteomics. GLRX5, GMPPB, and FUCA2 showed strong colocalization evidence and were supported by PWAS and transcript-level analysis, and were predominantly expressed in glutamatergic neuronal cells. In blood proteomics, one significant protein (PEAR1) and three near-significant proteins (NDE1, EVA1C, B4GALT2) were identified, but lacked colocalization evidence. Moreover, despite the limited correlation between the same protein in brain and blood, the PPI network analysis provided new insights into the interaction between brain and blood in SA. Furthermore, GLRX5 was associated with the GSTP1, the target of Clozapine. The comprehensive analysis provides strong evidence supporting a causal association between three genetically determined brain proteins (GLRX5, GMPPB, and FUCA2) with SA. These findings offer valuable insights into SA's underlying mechanisms and potential therapeutic approaches.

Stigma and its associations with medication adherence in major depressive disorder.

This study sought to evaluate internalized stigma (IS) and perceived stigma (PS), in persons (n = 522) living with major depressive disorder (MDD), with a view to analyzing the association of IS and PS with medication adherence in a cohort of participants with MDD in China. Perceived stigma is the awareness of societal negative views and attitudes towards depression, and IS is applying others' attitudes to oneself, both measured by the Depression Stigma Scale (DSS). Medication adherence was assessed using the Medication Adherence Rating Scale (MARS). We observed that 76.0 % of participants reported IS and 84.5 % reported PS. Factors associated with increased IS included older age, marital status, disease history, and a higher baseline Patient Health Questionnaire-9 (PHQ-9). Higher education level, family income, and scores on the Connor-Davidson Resilience Scale (CD-RISC) were associated with lower levels of IS. Higher education levels, Childhood Trauma Questionnaire (CTQ) scores, and living with others were also associated with higher PS, while engagement in exercise and higher number of prior episodes were associated with lower PS. IS had a negative association with medication adherence, whereas PS did not significantly associate with adherence. In conclusion, a testable hypothesis is derived from our data that strategies targeting IS amongst persons with MDD may improve overall rates of adherence to antidepressant treatment, a necessary prelude to improving recovery.

Impact of painful physical symptoms on first-episode major depressive disorder in adults with subthreshold depressive symptoms: A prospective cohort study.

OBJECTIVE: To investigate the impact of baseline painful physical symptoms (PPS) on subsequent first-episode major depressive disorder (MDD) in adults with subthreshold depressive symptoms, including subgroup analyses to assess whether the associations differ in individuals with and without physical diseases. METHODS: A total of 2343 adults with subthreshold depressive symptoms were recruited at 34 primary health care centers. PPS were measured at baseline. First-episode MDD during follow-up was diagnosed by professional psychiatrists using the Mini-International Neuropsychiatric Interview. RESULTS: Baseline PPS showed independent impacts on first-episode MDD in adults with subthreshold depressive symptoms without physical diseases, but not in those with physical diseases. A non-linear association (P < 0.001) was observed between PPS burden and the risk of first-episode MDD. The HRs for first-episode MDD exhibited a rapidly increasing trend between PPS burden scores of 10-16, and maintained consistently high when scores exceeded 16. The analyses for specific PPS revealed that headache, neck pain, and heart or chest pain were independently associated with first-episode MDD in participants without physical diseases, the HRs were 1.57 (1.15-2.36), 1.53 (1.02-2.30), and 1.69 (1.14-2.50), respectively. Further network analysis demonstrated that heart or chest pain serves as a bridge symptom among the seven specific PPS and first-episode MDD in those without physical diseases. CONCLUSION: PPS burden and heart or chest pain may be significant indicators for first-episode MDD in adults with subthreshold depressive symptoms without physical diseases. Future studies should investigate whether interventions targeting PPS can prevent episode MDD in this subthreshold population.

Evaluation of a novel instrument for detecting bipolar disorders in China: The Rapid Mood Screener (RMS).

OBJECTIVE: Bipolar disorder is easily misdiagnosed with major depressive disorder (MDD). The Rapid Mood Screener (RMS) was developed to address this unmet clinical need. This study aims to translate and evaluated the reliability and validity of the RMS in Chinese adults with bipolar I/II disorder (BD-I/II). METHODS: Brislin's translation and Delphi method were conducted to formulate the RMS-Chinses version (RMS-C). Patients with MDD (N = 99), BD-I (N = 77) and BD-II (N = 78) were included to assess the validity and reliability of RMS-C. The area under the curve (AUC) was computed to ascertain the ability of the Mood Disorder Questionnaire (MDQ) and RMS-C to distinguish BD-I and BD-II from MDD. The optimal cut-off scores for classification were also calculated by the maximum sensitivity and specificity. RESULTS: The intraclass correlation coefficient of the RMS-C was 0.82 (95%CI, 0.71-0.89). The content validity index by six items were 0.71, 0.86, 1.00, 0.86, 1.00, and 1.00 in turn, and by scales was 0.90. The AUCs of the RMS-C in both BD-I/II, BD-I alone and BD-II alone were 0.83 (95 % CI, 0.78-0.89), 0.82 (95 % CI, 0.75-0.89) and 0.85 (95 % CI, 0.79-0.91), respectively, and were comparably to the MDQ. The optimal RMS-C values of the presence of BD-I and BD-II were >4 and 3, respectively. CONCLUSION: The RMS-C is a valid, simple self-administer screening tool to help identify BD-I or BD-II in persons experiencing a depressive episode. Validating the impact of screening with the RMS-C on health outcomes and health economics is warranted.

The Effect of Internet-Based Cognitive Behavioral Therapy on Major Depressive Disorder: Randomized Controlled Trial.

BACKGROUND: Many people living with major depressive disorder (MDD) in China do not receive treatment owing to a lack of mental health services, along with significant stigma toward mental illness. Internet-based cognitive behavioral therapy (ICBT) has been proposed to increase access to mental health care for people with MDD. OBJECTIVE: The aims of this study were to (1) evaluate the efficacy of ICBT for depressive symptoms in patients with MDD; (2) evaluate the effect of ICBT on anxiety symptoms, nonspecific psychological distress, general self-efficacy, depression stigma, social function, and health-related quality of life (HRQoL); and (3) explore the acceptability of and satisfaction with the ICBT program among participants. METHODS: Patients with MDD were enrolled and randomized to the ICBT group or the waiting-list control (WLC) group. The ICBT group received ICBT delivered through a WeChat mini-program with general support by nonspecialists. Participants in the 2 groups were self-evaluated online at baseline and posttreatment for changes in the primary outcome (ie, depressive symptoms) and secondary outcomes (ie, anxiety symptoms, nonspecific psychological distress, general self-efficacy, depression stigma, social functional impairment, and HRQoL). Changes in outcomes were measured by changes in overall scores on respective scales, and response and remission rates were calculated based on depressive symptoms. The acceptability of and satisfaction with the ICBT program were measured by treatment adherence and participants' feelings (ie, modules seriously completed, perceived benefit, and satisfaction). RESULTS: We included 40 patients who were randomly assigned to the ICBT group and 44 who were assigned to the WLC group. Compared with the WLC group, the ICBT group had fewer depressive symptoms, fewer anxiety symptoms, less nonspecific psychological distress, and greater general self-efficacy. Moreover, the ICBT group had higher response (18/31, 58%) and remission rates (17/31, 55%). The adherence rate in the ICBT group was 78% (31/40), and the majority of participants who completed all ICBT modules were satisfied with the ICBT program. CONCLUSIONS: ICBT demonstrated greater improvements in depressive symptoms, anxiety symptoms, nonspecific psychological distress, and general self-efficacy among selected patients with MDD in comparison with the findings in waiting-list controls. The ICBT program in this study had good acceptability and satisfaction among participants. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100046425); https://tinyurl.com/bdcrj4zv.

Crosstalk between KIF1C and PRKAR1A in left atrial myxoma.

Cardiac myxoma (CM) is the most common benign cardiac tumor, and most CMs are left atrial myxomas (LAMs). Six variations of KIF1C, c.899 A > T, c.772 T > G, c.352 A > T, c.2895 C > T, c.3049 G > A, and c.*442_*443dup in left atrial myxoma tissues are identified by whole-exome sequencing (WES) and Sanger sequencing. RNA-seq and function experiments show the reduction of the expression of KIF1C and PRKAR1A caused by rare variations of KIF1C. KIF1C is observed to be located in the nucleus, bind to the promoter region of PRKAR1A, and regulate its transcription. Reduction of KIF1C decreases PRKAR1A expression and activates the PKA, which causes an increase in ERK1/2 phosphorylation and SRC-mediated STAT3 activation, a reduction of CDH1, TP53, CDKN1A, and BAX, and eventually promotes tumor formation both in vitro and in vivo. The results suggest that inhibition of KIF1C promotes the pathogenesis of LAM through positive feedback formed by the crosstalk between KIF1C and PRKAR1A.

Predictive potential of somatic symptoms for the identification of subthreshold depression and major depressive disorder in primary care settings.

Background: The presence of heterogenous somatic symptoms frequently obscures the recognition of depression in primary care. We aimed to explore the association between somatic symptoms and subthreshold depression (SD) and Major Depressive Disorder (MDD), as well as to determine the predictive potential of somatic symptoms in identifying SD and MDD in primary care. Methods: Data were derived from the Depression Cohort in China study (ChiCTR registry number: 1900022145). The Patient Health Questionnaire-9 (PHQ-9) was used to assess SD by trained general practitioners (GPs), and the Mini International Neuropsychiatric Interview depression module was used to diagnose MDD by professional psychiatrists. Somatic symptoms were assessed using the 28-item Somatic Symptoms Inventory (SSI). Results: In total of 4,139 participants aged 18-64 years recruited from 34 primary health care settings were included. The prevalence of all 28 somatic symptoms increased in a dose-dependent manner from non-depressed controls to SD, and to MDD (P for trend <0.001). Hierarchical clustering analysis grouped the 28 heterogeneous somatic symptoms into three clusters (Cluster 1: energy-related symptoms, Cluster 2: vegetative symptoms, and Cluster 3: muscle, joint, and central nervous symptoms). Following adjustment for potential confounders and the other two clusters of symptoms, per 1 increase of energy-related symptoms exhibited significant association with SD (OR = 1.24, 95% CI, 1.18-1.31) and MDD (OR = 1.50, 95% CI, 1.41-1.60) The predictive performance of energy-related symptoms in identifying individuals with SD (AUC = 0.715, 95% CI, 0.697-0.732) and MDD (AUC = 0.941, 95% CI, 0.926-0.963) was superior to the performance of total SSI and the other two clusters (P < 0.05). Conclusions: Somatic symptoms were associated with the presence of SD and MDD. In addition, somatic symptoms, notably those related to energy, showed good predictive potential in identifying SD and MDD in primary care. The clinical implication of the present study is that GPs should consider the closely related somatic symptoms for early recognition for depression in practice.

A novel vaccine targeting ß1-adrenergic receptor.

Beta-blockers are widely used in the treatment of hypertension, heart failure and ischemic heart disease. However, unstandardized medication results in diverse clinical outcomes in patients. The main causes are unattained optimal doses, insufficient follow-up and patients' poor adherence. To improve the medication inadequacy, our team developed a novel therapeutic vaccine targeting ß1-adrenergic receptor (ß1-AR). The ß1-AR vaccine named ABRQß-006 was prepared by chemical conjugation of a screened ß1-AR peptide with Qß virus like particle (VLP). The antihypertensive, anti-remodeling and cardio-protective effects of ß1-AR vaccine were evaluated in different animal models. The ABRQß-006 vaccine was immunogenic that induced high titers of antibodies against ß1-AR epitope peptide. In the NG-nitro-L-arginine methyl ester (L-NAME) + Sprague Dawley (SD) hypertension model, ABRQß-006 lowered systolic blood pressure about 10 mmHg and attenuated vascular remodeling, myocardial hypertrophy and perivascular fibrosis. In the pressure-overload transverse aortic constriction (TAC) model, ABRQß-006 significantly improved cardiac function, decreased myocardial hypertrophy, perivascular fibrosis and vascular remodeling. In the myocardial infarction (MI) model, ABRQß-006 effectively improved cardiac remodeling, reduced cardiac fibrosis and inflammatory infiltration, which was superior to metoprolol. Moreover, no significant immune-mediated damage was observed in immunized animals. The ABRQß-006 vaccine targeting ß1-AR showed the effects on hypertension and heart rate control, myocardial remodeling inhibition and cardiac function protection. These effects could be differentiated in different types of diseases with diverse pathogenesis. ABRQß-006 could be a novel and promising method for the treatment of hypertension and heart failure with different etiologies.

Vaccine Targeting Alpha 1D-Adrenergic Receptor Improved Metabolic Syndrome in Mice.

PURPOSE: Metabolic syndrome (MetS) is a complex chronic disease that includes obesity and hypertension, with rising evidence demonstrating that sympathetic nervous system (SNS) activation plays a key role. Our team designed a therapeutic vaccine called ADRQß-004 targeting the α1D-adrenergic receptor (α1D-AR). This study was performed to investigate whether the ADRQß-004 vaccine improves MetS by modulating SNS activity. METHODS: C57BL/6N mice were fed a high-fat diet (HFD) and Nω-nitro-L-arginine methyl ester (L-NAME) combination diet for 18 weeks to elicit MetS. The MetS mice were subcutaneously immunized with the ADRQß-004 vaccine four times to evaluate the therapeutic efficacy in obesity and hypertension and other associated abnormalities related to MetS by conducting echocardiographic, histological, and biochemical analyses. RESULTS: The ADRQß-004 vaccine induced strong antibody production and maintained a high anti-ADR-004 antibody titer in MetS mice. The ADRQß-004 vaccine improved obesity (P < 0.001) and decreased systolic blood pressure (P < 0.001). Improvements in dysregulated glucose homeostasis and dyslipidemia resulting from the ADRQß-004 vaccine were also confirmed. Furthermore, the ADRQß-004 vaccine attenuated cardiovascular functional (P = 0.015) and structural changes (P < 0.001), decreased fat accumulation (P = 0.012) and inflammation (P = 0.050) in the epididymal white adipose tissue, and alleviated hepatic steatosis (P = 0.043) involved in MetS. Moreover, the ADRQß-004 vaccine improved systematic and visceral organs SNS activities in the MetS. CONCLUSION: This study demonstrated for the first time that the ADRQß-004 vaccine targeting α1D-AR improved obesity, hypertension, dyslipidemia, and dysglycemia, and further reduced end-organ damage, which may provide new motivation for MetS research.

Associations of stressful life events with subthreshold depressive symptoms and major depressive disorder: The moderating role of gender.

BACKGROUND: Stressful life events (SLEs) are high-risk factors for subthreshold depressive symptoms (SDS) and major depressive disorder (MDD). This study sought to assess the association of SLEs with SDS and MDD, with a focus on gender effects. METHODS: A total of 4132 participants were recruited from 34 primary health care settings. The Stressful Life Events Screening Questionnaire (SLESQ) was used to measure SLEs that participants had experienced in the past time. The Patient Health Questionnaire 9 (PHQ-9) was used to assess SDS, and the Mini-International Neuropsychiatry Interview (MINI) depression module was used to assess the diagnosis of MDD by trained psychiatrists. RESULTS: In our sample (N = 4132), exposure to any SLEs was more common in individuals with SDS and MDD than in non-depressed population, and the proportion of emotional abuse was relatively high (SDS: 10.6 %; MDD: 33.9 %). After adjusting for control variables, people who experienced SLEs were at a higher risk of SDS and MDD. For males, those experiencing only one event were not at a higher risk of SDS (P = 0.061). For individuals who had experienced multiple SLEs, the association between SLEs and SDS was stronger in females than males. However, the association between SLEs and MDD was stronger in males than females. LIMITATIONS: The cross-sectional study design and self-reported SLEs. CONCLUSIONS: SLEs were associated with the increased risks of SDS and MDD. The associations of SLEs with SDS were more robust for females than males. In contrast, the association between SLEs and MDD was stronger in males than females.

Peptide Vaccine Against ADAMTS-7 Ameliorates Atherosclerosis and Postinjury Neointima Hyperplasia.

BACKGROUND: The metalloprotease ADAMTS-7 (a disintegrin and metalloproteinase with thrombospondin type 1 motif 7) is a novel locus associated with human coronary atherosclerosis. ADAMTS-7 deletion protects against atherosclerosis and vascular restenosis in rodents. METHODS: We designed 3 potential vaccines consisting of distinct B cell epitopic peptides derived from ADAMTS-7 and conjugated with the carrier protein KLH (keyhole limpet hemocyanin) as well as aluminum hydroxide as an adjuvant. Arterial ligation or wire injury was used to induce neointima in mice, whereas ApoE-/- and LDLR-/- (LDLR [low-density lipoprotein receptor]) mice fed a high-fat diet were applied to assess atherosclerosis. In addition, coronary stent implantation was performed on vaccine-immunized Bama miniature pigs, followed by optical coherence tomography to evaluate coronary intimal hyperplasia. RESULTS: A vaccine, ATS7vac, was screened out from 3 candidates to effectively inhibit intimal thickening in murine carotid artery ligation models after vaccination. As well, immunization with ATS7vac alleviated neointima formation in murine wire injury models and mitigated atherosclerotic lesions in both hyperlipidemic ApoE-/- and LDLR-/- mice without lowering lipid levels. Preclinically, ATS7vac markedly impeded intimal hyperplasia in swine stented coronary arteries, but without significant immune-related organ injuries. Mechanistically, ATS7vac vaccination produced specific antibodies against ADAMTS-7, which markedly repressed ADAMTS-7-mediated COMP (cartilage oligomeric matrix protein) and TSP-1 (thrombospondin-1) degradation and subsequently inhibited vascular smooth muscle cell migration but promoted re-endothelialization. CONCLUSIONS: ATS7vac is a novel atherosclerosis vaccine that also alleviates in-stent restenosis. The application of ATS7vac would be a complementary therapeutic avenue to the current lipid-lowering strategy for atherosclerotic disease.

Association between childhood trauma and medication adherence among patients with major depressive disorder: the moderating role of resilience.

BACKGROUND: Suboptimal medication adherence is a major reason for failure in the management of major depressive disorder (MDD), childhood trauma might be an essential risk factor of suboptimal medication adherence. This study aimed to comprehensively explore the associations between different types of childhood trauma and medication adherence among patients with MDD, and to test whether resilience has moderating effects on the foregoing associations. METHODS: Participants were from the Depression Cohort in China (ChiCTR registry number 1900022145), 282 MDD patients with completed both baseline and 12-weeks follow-up investigations were included in this study. The diagnosis of MDD was assessed by trained psychiatrists using the Mini-International Neuropsychiatric Interview (M.I.N.I.). Childhood trauma was evaluated using the Childhood Trauma Questionnaire-28 item Short Form (CTQ-SF), and resilience was evaluated using the Connor-Davidson Resilience Scale (CD-RISC). Demographic characteristics, depression symptoms, anxiety symptoms, suicidal ideation, suicidal attempt, insomnia symptoms, and painful somatic symptoms were also investigated. Participants were divided into groups of optimal and suboptimal adherence based on their Medication Adherence Rating Scale scores. Logistic regression and stratified analyses were performed. RESULTS: A total of 234 participants (83%) reported suboptimal medication adherence. After adjusting for covariates, CTQ total scores (AOR = 1.03, 95%CI = 1.01-1.06), CTQ measures of sexual abuse (AOR = 1.17, 95%CI = 1.01-1.37), and CTQ measures of physical neglect (AOR = 1.12, 95%CI = 1.02-1.23) were all associated with an increased likelihood of suboptimal adherence. There were significant moderating effects of resilience on the associations of childhood trauma (P = 0.039) and physical neglect (P = 0.034) with medication adherence. The stratification analyses showed that CTQ total scores and CTQ measures of physical neglect were independently associated with an increased risk of suboptimal adherence among patients with MDD with low-resilience or moderate-resilience, while not significantly associated with suboptimal adherence in those with high-resilience. CONCLUSION: Childhood trauma was a significant risk factor of suboptimal adherence among patients with MDD, and resilience moderated the foregoing association. Obtaining a history of childhood trauma and assessing resilience may help identify patients with suboptimal adherence when providing MDD pharmacotherapy. Psychiatrists may consider enhancing resilience to cope with the adverse effects of childhood trauma on medication adherence.

Clinical characteristics and 1-year outcomes in hospitalized patients with heart failure with preserved ejection fraction: results from the China Cardiovascular Association Database-Heart Failure Center Registry.

AIM: We aimed to evaluate clinical characteristics and 1-year outcomes in hospitalized patients with heart failure with preserved ejection fraction (HFpEF) from China. Factors associated with outcomes (hospitalization for HF [HHF] and cardiovascular [CV] death) were assessed. METHOD AND RESULTS: Data were from the China Cardiovascular Association (CCA) Database-HF Center Registry. Between January 2017 and June 2021, 41 708 hospitalized HFpEF patients with 1-year follow-up from 481 CCA Database-HF Center certified secondary and tertiary hospitals across overall 31 provinces of mainland China were included in this study. Of study participants (mean age 72.2 years, 49.3% female), 18.2% had HHF in prior 1 year and 55.8% had New York Heart Association class III/IV. Median left ventricular ejection fraction was 59%. Ischaemia (26.6%), infection (14.4%) and arrhythmia (10.5%) were the three most common precipitating factors for index HHF. Nearly 67.4% had ≥3 comorbidities. Hypertension (65.2%), coronary heart disease (60.3%) and atrial fibrillation (41.2%) were the three most common comorbidities. Device and medication therapy non-compliance with current HF guideline recommendation was observed. The 1-year rate of clinical outcomes was 16.4%, the 1-year rate of HHF was 13.6% and CV death was 3.1%. Factors associated with clinical outcomes included HHF in prior 1 year, serum level of sodium <135 mmol/L and N-terminal pro-B-type natriuretic peptide >1800 pg/ml. CONCLUSION: Patients with HFpEF from China were characterized by high comorbid burden and high 1-year risk of HHF and CV death. Immediate efforts are needed to improve HFpEF management in China.

Impact of cognitive-affective and somatic symptoms in subthreshold depression transition in adults: Evidence from Depression Cohort in China (DCC).

BACKGROUND: Symptoms of subthreshold depression may differentially affect the illness transition. We examined the impact of cognitive-affective and somatic symptoms on different subthreshold depression transitions as well as risk factors influencing the aforementioned symptoms changes. METHODS: Adults with subthreshold depression in the Depression Cohort in China were enrolled. Data collection was conducted at baseline, 6 and 12 months from 2019 to 2020. Cognitive-affective and somatic symptoms were assessed using the Patient Health Questionnaire-9. A total of 993 participants completed 12-month follow-up and were divided into persistent, intermittent and remission groups according to change in depressive symptoms. The longitudinal change of cognitive-affective and somatic symptoms in the three groups, as well as risk factors was analyzed using the generalized linear mixed-model. RESULTS: There were 24.07 %, 34.04 % and 41.89 % of participants proceeding into persistent, intermittent and remission subthreshold depression groups, respectively. Cognitive-affective symptoms were the core symptoms for predicting the deterioration in persistent subthreshold depression (t = 2.48, P = 0.013), whereas somatic symptoms improved over time (t = -2.82, P = 0.005). Anxiety symptoms were the primary risk factors for worsening cognitive-affective symptoms (P < 0.001), following by insomnia symptoms, age, marital status, resilience and social functions. Somatic symptoms were affected by insomnia symptoms, anxiety symptoms and Body Mass Index successively. LIMITATIONS: Major Depressive Episode was not explored in follow-up. CONCLUSION: Cognitive-affective symptoms in subthreshold depression are at greater risk of illness deterioration. Future studies should endeavor to identify specific risk factors in different symptoms to forestall the transition from subthreshold to Major Depressive Disorder.