Accuracy and longitudinal consistency of PET/MR attenuation correction in amyloid PET imaging amid software and hardware upgrades.

BACKGROUND AND PURPOSE: Integrated PET/MR allows the simultaneous acquisition of PET biomarkers and structural and functional MRI to study Alzheimer disease (AD). Attenuation correction (AC), crucial for PET quantification, can be performed using a deep learning approach, DL-Dixon, based on standard Dixon images. Longitudinal amyloid PET imaging, which provides important information about disease progression or treatment responses in AD, is usually acquired over several years. Hardware and software upgrades often occur during a multiple-year study period, resulting in data variability. This study aims to harmonize PET/MR DL-Dixon AC amid software and head coil updates and evaluate its accuracy and longitudinal consistency. MATERIALS AND METHODS: Tri-modality PET/MR and CT images were obtained from 329 participants, with a subset of 38 undergoing tri-modality scans twice within approximately three years. Transfer learning was employed to fine-tune DL-Dixon models on images from two scanner software versions (VB20P and VE11P) and two head coils (16-channel and 32-channel coils). The accuracy and longitudinal consistency of the DL-Dixon AC were evaluated. Power analyses were performed to estimate the sample size needed to detect various levels of longitudinal changes in the PET standardized uptake value ratio (SUVR). RESULTS: The DL-Dixon method demonstrated high accuracy across all data, irrespective of scanner software versions and head coils. More than 95.6% of brain voxels showed less than 10% PET relative absolute error in all participants. The median [interquartile range] PET mean relative absolute error was 1.10% [0.93%, 1.26%], 1.24% [1.03%, 1.54%], 0.99% [0.86%, 1.13%] in the cortical summary region, and 1.04% [0.83%, 1.36%], 1.08% [0.84%, 1.34%], 1.05% [0.72%, 1.32%] in cerebellum using the DL-Dixon models for the VB20P-16-channel-coil, VE11P-16-channel-coil and VE11P-32-channel-coil data, respectively. The within-subject coefficient of variation and intra-class correlation coefficient of PET SUVR in the cortical regions were comparable between the DL-Dixon and CT AC. Power analysis indicated that similar numbers of participants would be needed to detect the same level of PET changes using DL-Dixon and CT AC. CONCLUSIONS: DL-Dixon exhibited excellent accuracy and longitudinal consistency across the two software versions and head coils, demonstrating its robustness for longitudinal PET/MR neuroimaging studies in AD. ABBREVIATIONS: AC = attenuation correction; AD = Alzheimer disease; HU = Hounsfield unit; ICC = intraclass correlation coefficient; MAE = mean absolute error; MRAE = mean relative absolute error; pCT = pseudo-CT; PiB = Pittsburgh Compound B; SD = standard deviation; SUVR = standardized uptake value ratio; wCV = within-subject coefficient of variation.

Diterpenoids of Caryopteris trichosphaera W. W. Sm. inhibiting MRSA and VRE in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Caryopteris trichosphaera W. W. Sm., a traditional ethnic medicine, was recorded in the Compendium of Materia Medica for treating wound infection by pathogenic infection. However, its antibacterial potential and bioactive compositions against drug-resistant bacteria need to be validated. AIM OF THE STUDY: To investigate the chemical constituents of C. trichosphaera and explore its anti-MRSA component in vitro and in vivo, together with the antibacterial mechanism. MATERIALS AND METHODS: Bioactive constituents investigation was carried out by phytochemical method and antibacterial screening. The antibacterial mechanism was predicted by network pharmacology, which was further validated by time-kill analysis, membrane function tests, multigenerational resistance induction assay and biofilm test, and metabolomics analysis in vitro. In addition, MRSA-induced epidermal infection in mice was selected to evaluate its pharmacological effect in vivo. RESULTS: Six antibacterial diterpenoids against MRSA and VRE with MIC values 4-32 µg/mL from C. trichosphaera were reported for the first time, in which the major compound cativic acid (1) disrupted MRSA cell membranes by modulating permeability, depolarization, and fluidity while increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels. It also displayed remarkable anti-biofilm activity without inducing bacterial resistance or cytotoxicity. Moreover, cativic acid affected MRSA biosynthesis of cofactors, amino acid biosynthesis, nucleotide metabolism by metabolomics analysis. Furthermore, cativic acid accelerated wound healing in MRSA-infected mouse skin wounds, even better than vancomycin. CONCLUSIONS: The results supported the traditional use of C. trichosphaera, and presented unreported anti-MRSA agent, cativic acid, as a plant-derived bactericide in vitro and in vivo for the first time.

Gut and respiratory microbiota landscapes in IgA nephropathy: a cross-sectional study.

BACKGROUND: IgA nephropathy (IgAN) is intimately linked to mucosal immune responses, with nasopharyngeal and intestinal lymphoid tissues being crucial for its abnormal mucosal immunity. The specific pathogenic bacteria in these sites associated with IgAN, however, remain elusive. Our study employs 16S rRNA sequencing and machine learning (ML) approaches to identify specific pathogenic bacteria in these locations and to investigate common pathogens that may exacerbate IgAN. METHODS: In this cross-sectional analysis, we collected pharyngeal swabs and stool specimens from IgAN patients and healthy controls. We applied 16SrRNA sequencing to identify differential microbial populations. ML algorithms were then used to classify IgAN based on these microbial differences. Spearman correlation analysis was employed to link key bacteria with clinical parameters. RESULTS: We observed a reduced microbial diversity in IgAN patients compared to healthy controls. In the gut microbiota of IgAN patients, increases in Bacteroides, Escherichia-Shigella, and Parabacteroides, and decreases in Parasutterella, Dialister, Faecalibacterium, and Subdoligranulum were notable. In the respiratory microbiota, increases in Neisseria, Streptococcus, Fusobacterium, Porphyromonas, and Ralstonia, and decreases in Prevotella, Leptotrichia, and Veillonella were observed. Post-immunosuppressive therapy, Oxalobacter and Butyricoccus levels were significantly reduced in the gut, while Neisseria and Actinobacillus levels decreased in the respiratory tract. Veillonella and Fusobacterium appeared to influence IgAN through dual immune loci, with Fusobacterium abundance correlating with IgAN severity. CONCLUSIONS: This study revealing that changes in flora structure could provide important pathological insights for identifying therapeutic targets, and ML could facilitate noninvasive diagnostic methods for IgAN.

Seabuckthorn polysaccharides mitigate hepatic steatosis by modulating the Nrf-2/HO-1 pathway and gut microbiota.

Non-alcoholic fatty liver disease (NAFLD) is becoming a significant global public health threat. Seabuckthorn (Hippophae rhamnoides L.) has been used in traditional Chinese medicine (TCM). The hypolipidemic effects of Seabuckthorn polysaccharides (SP) against high-fat diets (HFD)-induced NAFLD were systematically explored and compared with that of Bifidobacterium lactis V9 (B. Lactis V9). Results showed that HFD-induced alanine transaminase (ALT) and aspartate aminotransferase (AST) levels decreased by 2.8-fold and 4.5-fold, respectively, after SP supplementation. Moreover, the alleviating effect on hepatic lipid accumulation is better than that of B. Lactis V9. The ACC and FASN mRNA levels were significantly reduced by 1.8 fold (P < 0.05) and 2.3 folds (P < 0.05), respectively, while the CPT1α and PPARα mRNA levels was significantly increased by 2.3 fold (P < 0.05) and 1.6 fold (P < 0.05), respectively, after SP administration. SP activated phosphorylated-AMPK and inhibited PPARγ protein expression, improved serum oxidative stress and inflammation (P < 0.05). SP supplementation leads to increased hepatic expression of nuclear factor erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1) and Superoxide dismutase-2 (SOD-2). Furthermore, SP treatment improved HFD-induced intestinal dysbiosis. Lentisphaerae, Firmicutes, Tenericutes and Peptococcus sp., RC9_gut_group sp., and Parabacteroides sp. of the gut microbiota were significantly associated with hepatic steatosis and indicators related to oxidative stress and inflammation. Therefore, SP can mitigate hepatic lipid accumulation by regulating Nrf-2/HO-1 signaling pathways and gut microbiota. This study offers new evidence supporting the use of SP as a prebiotic treatment for NAFLD.

[Research Progress in Examination Methods,Influencing Factors, and Drug Treatment of Vigilance].

Vigilance is a sensitive ability to respond to small changes in the environment and it is a major component of various cognitive performance tasks.Professionals in a variety of fields require high physical and vigilance performance during the working process to ensure productivity,workplace safety,and their own safety. This article reviews the research progress in vigilance in terms of the examination methods,influencing factors,and drug treatment in recent years,aiming to improve the understanding of vigilance and provide support for the research on vigilance and clinical treatment of vigilance-related dysfunctions.

Immunological roles for resistin and related adipokines in obesity-associated tumors.

Rationale Obesity is an independent risk factor for the occurrence and development of tumors. Obesity is influenced by signaling of adipokines, which are secreted factors from adipocytes and resident immune cells within adipose tissues that mediate lipid metabolism. More recently, adipokines have been implicated in chronic inflammation as well as in tumor formation and growth. Among them, resistin has received increasing attention in research related to the growth and expansion of solid tumors and hematological cancers through various signaling pathways. Objective and findings We reviewed the physiological, biochemical, and immune functions of adipose tissue, with a focus on the structure and expression of resistin and adipokines within multiple adipose cell types, their signaling pathways and putative effects on tumor cells, as well as their in vivo regulation. Current evidence indicates that adipokines such as resistin act as pro-inflammatory factors to stimulate immune cells which, in turn, promotes tumor angiogenesis, connective tissue proliferation, and matrix fibrosis. Concurrently, in states of metabolic dysfunction and lipotoxicity in obese individuals, the numbers and functions of immune cells are compromised, leading to an immunosuppressive environment that fosters tumor cell survival and weak cancer immune monitoring. Conclusion Adipokines such as resistin are important to the development of obesity-related tumors. Clarifying the roles for obesity-related factors in immune regulation and tumor progression may lead to the discovery of novel anti-tumor strategies for targeting obesity factors such as resistin to limit tumor growth and manage obesity, or both.

[Effects of Streptomyces pactum Act12 on root morphogenesis and medicinal quality of Codonopsis pilosula]. / 密旋链霉菌Act12å¯¹å šå‚æ ¹ç³»å½¢æ€åŠè¯æå“è´¨çš„å½±å“.

As a kind of tonic Chinese medicine with dual use in medicine and food, there is a large market demanding for Codonopsis pilosula. Taking one-year-old C. pilosula seedlings as materials, we conducted a field experiment to examine the effect of compound fertilizer (750 kg·hm-2), organic fertilizer (15 t·hm-2) and Streptomyces pactum Act12 agent (9 t·hm-2 Act12+10 t·hm-2 organic fertilizer) treatments on root morphology, secondary metabolite content and expression level of lobetyolin metabolic pathway gene of C. pilosula, to clarify the effects of three fertilizers on the root morphology and medicinal quality. Compared to the control (10 t·hm-2 organic fertilizer, conventional fertilization), three fertilization treatments could promote root growth and formation. All fertilization treatments promoted the accumulation of C. pilosula polysaccharides and secondary metabolites. Act12 agent significantly increased the content of lobetyolin, atractylenolideIII, and 5-hydroxymethylfurfural. The qRT-PCR analysis indicated that three fertilization treatments increased the expression level of lobetyolin metabolic pathway genes, with Act12 agent treatment showing the most significant effect. Pearson correlation analysis demonstrated that the expression level of CpHCT and CpFAD genes was significantly positively correlated with atractylenolide III content. In conclusion, three fertilization treatments could effectively improve the yield and quality of C. pilosula. Among the three treatments, Act12 agent performed better than that of compound fertilizer and organic fertilizer, which was an effective measure to increase the yield and quality of C. pilosula.

Integrating Metal-Phenolic Networks-Mediated Separation and Machine Learning-Aided Surface-Enhanced Raman Spectroscopy for Accurate Nanoplastics Quantification and Classification.

Increasing accumulation of nanoplastics across ecosystems poses a significant threat to both terrestrial and aquatic life. Surface-enhanced Raman scattering (SERS) is an emerging technique used for nanoplastics detection. However, the identification and classification of nanoplastics using SERS faces challenges regarding sensitivity and accuracy as nanoplastics are sparsely dispersed in the environment. Metal-phenolic networks (MPNs) have the potential to rapidly concentrate and separate various types and sizes of nanoplastics. SERS combined with machine learning may improve prediction accuracy. Herein, we report the integration of MPNs-mediated separation with machine learning-aided SERS methods for the accurate classification and high-precision quantification of nanoplastics, which is tailored to include the complete region of characteristic peaks across diverse nanoplastics in contrast to the traditional manual analysis of SERS spectra on a singular characteristic peak. Our customized machine learning system (e.g., outlier detection, classification, quantification) allows for the identification of detectable nanoplastics (accuracy 81.84%), accurate classification (accuracy > 97%), and sensitive quantification of various types of nanoplastics (polystyrene (PS), poly(methyl methacrylate) (PMMA), polyethylene (PE), and poly(lactic acid) (PLA)) down to ultralow concentrations (0.1 ppm) as well as accurate classification (accuracy > 92%) of nanoplastic mixtures at a subppm level. The effectiveness of this approach is substantiated by its ability to discern between different nanoplastic mixtures and detect nanoplastic samples in natural water systems.

Association between serum potassium, risk and prognosis of peritonitis in peritoneal dialysis patients - results from the Peritoneal Dialysis Telemedicine-assisted Platform Cohort (PDTAP) Study.

BACKGROUND: Hypokalemia has been associated with an increased risk of peritoneal dialysis (PD)-associated peritonitis. However, hypokalemia is commonly associated with malnutrition, inflammation, and severe coexisting comorbidities, which thus are suspected of being potential confounders. This study was aimed at testing whether hypokalemia was independently associated with the occurrence and prognosis of PD-associated peritonitis. METHODS: A national-level dataset from the Peritoneal Dialysis Telemedicine-assisted Platform Cohort (PDTAP) Study was used to explore the independent association of serum potassium with PD-associated peritonitis. Unmatched and propensity score-adjusted multivariate competing risk models, as well as univariate competing risk models following 1:1 propensity score matching, were conducted to balance potential biases between patients with and without hypokalemia. The association between potassium levels prior to peritonitis and treatment failure due to peritonitis was also investigated. RESULTS: During a median follow-up of 25.7 months in 7220 PD patients, there was a higher incidence of peritonitis in patients with serum potassium below 4.0 mmol/L compared to those with higher serum levels (677 [0.114/patient-year] vs. 914 [0.096/patient-year], P = 0.001). After adjusting for demographics, laboratory tests, residual renal function, and medication use, baseline potassium levels below 4.0 mmol/L were not linked to an increased risk of peritonitis, with a hazard ratio of 0.983 (95% CI 0.855-1.130, P = 0.810). This result remained consistent in both the propensity score adjusted multivariate competing risk regression (HR = 0.974, 95% CI 0.829-1.145, P = 0.750) and the univariate competing risk regression after 1:1 propensity score matching (Fine-Gray test, P = 0.218). The results were similar when analyzing patients with serum potassium level above or below 3.5 mmol/L. Lastly, hypokalemia before the occurrence of peritonitis was not independently associated with treatment failure. CONCLUSION: Hypokalemia was not found to be an independent risk factor for PD-associated peritonitis or treatment failure of peritonitis in China.

Symptom Dimensions and Cognitive Impairments in Individuals at Clinical High Risk for Psychosis.

OBJECTIVE: Understanding the intricate relationship between symptom dimensions, clusters, and cognitive impairments is crucial for early detection and intervention in individuals at clinical high-risk(CHR) for psychosis. This study delves into this complex interplay within a CHR sample and aims to predict the conversion to psychosis. METHODS: A comprehensive cognitive assessment was performed among 744 CHR individuals. The study included a three-year follow-up period to assess conversion to psychosis. Symptom profiles were determined using the Structured Interview for Prodromal Syndromes. By applying factor analysis, symptom dimensions were categorized as dominant negative symptoms(NS), positive symptoms-stressful(PS-S), and positive symptoms-odd(PS-O). The factor scores were used to define three dominant symptom groups. Latent class analysis(LCA) and factor mixture model(FMM) were employed to identify discrete clusters based on symptom patterns. The three-class solution was chosen for the LCA and FMM analysis. RESULTS: Individuals in the dominant NS group exhibited significantly higher conversion rates to psychosis than those in the other groups. Specific cognitive variables, including performance in the Brief Visuospatial Memory Test-Revised(Odd ratio, OR=0.702, p=0.001) and Neuropsychological Assessment Battery mazes(OR=0.776, p=0.024), significantly predicted conversion to psychosis. Notably, cognitive impairments associated with NS and PS-S affected different cognitive domains. LCA- and FMM-Cluster 1, characterized by severe NS and PS-O, exhibited more impairments in cognitive domains than other clusters. No significant difference in the conversion rate was observed among LCA and FMM clusters. CONCLUSIONS: These findings highlight the importance of NS in the development of psychosis and suggest specific cognitive domains that are affected by symptom dimensions.

Bioinformatics and experimental validation were combined to explore lactylation-related biomarkers in HBV-associated acute liver failure.

BACKGROUND AND AIM: Currently, hepatitis B virus-related acute liver failure (HBV-ALF) has limited treatment options. Studies have shown that histone lactylation plays a role in the progression of liver-related diseases. Therefore, it is essential to explore lactylation-related gene (LRGs) biomarkers in HBV-ALF to provide new information for the treatment of HBV-ALF. METHODS: Two HBV-ALF-related datasets (GSE38941 and GSE14668) and 65 LRGs were used. First, the differentially expressed genes (DEGs) were derived from differential expression analysis, the key module genes from weighted gene co-expression network analysis; and LRGs were used to intersect to obtain the candidate genes. Subsequently, the feature genes obtained from least absolute shrinkage and selection operator regression analysis and support vector machine analysis were intersected to obtain the candidate key genes. Among them, genes with consistent and significant expression trends in both GSE38941 and GSE14668 were used as biomarkers. Subsequently, biomarkers were analyzed for functional enrichment, immune infiltration, and sensitive drug prediction. RESULTS: In this study, five candidate genes (PIGM, PIGA, EGR1, PIGK, and PIGL) were identified by intersecting 6461 DEGs and 2496 key module genes with 65 LRGs. We then screened four candidate key genes from the machine learning algorithm, among which PIGM and PIGA were considered biomarkers in HBV-ALF. Moreover, the results of enrichment analysis showed that the significant enrichment signaling pathways for biomarkers included allograft rejection and valine, leucine, and isoleucine degradation. Thereafter, 11 immune cells differed significantly between groups, with resting memory CD4+ T cells having the strongest positive correlation with biomarkers. Methylphenidate hydrochloride is a potential therapeutic drug for PIGM. CONCLUSION: Two genes, PIGM and PIGA, were identified as biomarkers related to LRGs in HBV-ALF, providing a basis for understanding HBV-ALF pathogenesis.

Efficient elimination of antibiotics and antibiotic resistance genes in hyperthermophilic sludge composting.

Composting is widely applied in recycling ever-increasing sewage sludge. However, the insufficient elimination of antibiotics and antibiotic resistance genes (ARGs) in conventional compost fertilizer poses considerable threat to agriculture safety and human health. Here we investigated the efficacy and potential mechanisms in the removal of antibiotics and ARGs from sludge in hyperthermophilic composting (HTC) plant. Our results demonstrated that the HTC product was of high maturity. HTC led to complete elimination of antibiotics and potential pathogens, as well as removal of 98.8 % of ARGs and 88.1 % of mobile genetic elements (MGEs). The enrichment of antibiotic-degrading candidates and related metabolic functions during HTC suggested that biodegradation played a crucial role in antibiotic removal. Redundancy analysis (RDA) and structural equation modelling (SEM) revealed that the reduction of ARGs was attributed to the decline of ARG-associated bacteria, mainly due to the high-temperature selection. These findings highlight the feasibility of HTC in sludge recycling and provide a deeper understanding of its mechanism in simultaneous removal of antibiotics and ARGs.

Adriamycin-induced podocyte injury via the Sema3A/TRPC5/Rac1 pathway.

Podocytopathies encompass kidney diseases where direct or indirect podocyte injury leads to proteinuria or nephrotic syndrome. Although Semaphorin3A (Sema3A) is expressed in podocytes and tubular cells in adult mammalian kidneys and has a common effect on the progression of podocyte injury, its mechanism remains unclear. Previous studies have shown increased Sema3A expression in various glomerulopathies, indicating a gap in understanding its role. In this study, analysis of human data revealed a positive correlation between the levels of urinary Sema3A and Podocalyxin (PCX), suggesting a close relationship between Sema3A and podocyte loss. Furthermore, the impact of Adriamycin on podocytes was investigated. Adriamycin induced podocyte migration and apoptosis, along with an increase in Sema3A expression, all of which were ameliorated by the inhibition of Sema3A. Importantly, TRPC5 was found to increase the overexpression of Sema3A in podocytes. A TRPC5 inhibitor, AC1903, alleviated podocyte migration and apoptosis, inhibiting the formation of lamellar pseudopodia in the podocyte cytoskeleton by lowering the expression of Rac1. Furthermore, AC1903 relieved massive albuminuria and foot process effacement in the kidneys of Adriamycin-treated mice in vivo. In conclusion, our findings suggest that Sema3A may impact the cytoskeletal stability of podocytes through TRPC5 ion channels, mediated by Rac1, ultimately leading to foot process effacement. Notably, AC1903 demonstrates the potential to reverse Adriamycin-induced foot process fusion and urine protein. These results contribute to a deeper understanding of the mechanisms involved in podocytopathies and highlight the therapeutic potential of targeting the Sema3A-TRPC5 pathway.

Dual-Mode Reconfigurable Split-Gate Logic Transistor through Van der Waals Integration.

As silicon-based transistors approach their physical size limitations, two-dimensional material-based reconfigurable functional electronic devices are considered the most promising novel device architectures beyond Moore strategies. While these devices have garnered significant attention, they often require complex device fabrication processes and extra electric fields. Additionally, the device performance is usually limited by the metal-semiconductor interface properties. In this Letter, we have constructed a reconfigurable logic device based on a WSe2 transistor with a nanofloating gate and split-gates through van der Waals integration. This device achieves a small Schottky barrier height due to the van der Waals contacts. By varying the split-gate biases, we can realize volatile reconfigurable homojunctions as well as AND, OR, NOR, and NAND logic operations with just a single device. Furthermore, with the charge trapping effect of nanofloating gate, we can also achieve nonvolatile reconfigurable homojunctions, as well as AND and OR logic operations. The volatile and nonvolatile logic operations are similar to the short-term plasticity and long-term plasticity, respectively, of synapses in the human brain. This work offers a potential approach for creating novel reconfigurable functional electronic devices with a simple fabrication process and low cost.

Correction: Bioreducible and acid-labile polydiethylenetriamines with sequential degradability for efficient transgelin-2 siRNA delivery.

Correction for 'Bioreducible and acid-labile polydiethylenetriamines with sequential degradability for efficient transgelin-2 siRNA delivery' by Pengchong Wang et al., J. Mater. Chem. B, 2019, 7, 6994-7005, https://doi.org/10.1039/C9TB01183H.

The imaging manifestations of persistent truncus arteriosus in children.

Persistent truncus arteriosus (PTA) is a rare congenital heart malformation. A 4-year-old girl was diagnosed with type I PTA through echocardiography and confirmed by cardiac CTA.

In-Hospital Mortality and Treatment in Patients With Acute Coronary Syndrome With and Without Standard Modifiable Cardiovascular Risk Factors: Findings From the CCC-ACS Project.

BACKGROUND: Patients with acute coronary syndrome without standard modifiable cardiovascular risk factors (SMuRFs; hypertension, smoking, dyslipidemia, diabetes) have not been well studied, with little known about their characteristics, quality of care, or outcomes. We sought to systematically analyze patients with ACS without SMuRFs, especially to evaluate the effectiveness of guideline-directed medical therapy for these patients. METHODS AND RESULTS: In the CCC-ACS (Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome) project (2014-2019), we examined the presence and absence of SMuRFs and features among 89 462 patients with initial acute coronary syndrome. The main outcome was in-hospital all-cause mortality. Among eligible patients, 11.0% had none of the SMuRFs (SMuRF-less). SMuRF-less patients had higher in-hospital mortality (unadjusted hazard ratio [HR], 1.49 [95% CI, 1.19-1.87]). After adjustment for clinical characteristics and treatments, the associations between SMuRF status and in-hospital mortality persisted (adjusted HR, 1.35 [95% CI, 1.07-1.70]). Guideline-directed optimal medical therapy (receiving angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, ß-blockers, and statins) was not associated with lower mortality (adjusted HR, 0.98 [95% CI, 0.58-1.67]) in SMuRF-less patients, unlike the association in patients with SMuRFs (adjusted HR, 0.80 [95% CI, 0.66-0.98]). Sensitivity analyses were consistent with these results. CONCLUSIONS: SMuRF-less patients were associated with an increased risk of in-hospital mortality. Guideline-directed medical therapy was less effective in SMuRF-less patients than in patients with SMuRFs. Dedicated studies are needed to confirm the optimal therapy for SMuRF-less patients. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02306616.

Association Between Phthalates Exposure and All-Cause Mortality Among Diabetic Cases: A Prospective Study.

The aim of this study was to explore the association between phthalates (PAEs) exposure and all-cause mortality among diabetic cases, and potential molecular mechanisms of the effect. We followed 2806 diabetes cases from 2008 to the end of 2018 based on the Dongfeng-Tongji study, of which 446 cases died. We measured serum levels of six PAEs (DMP, DEP, DiBP, DnBP, BBP, and DEHP). Cox models were used to investigate the associations between PAEs and all-cause mortality. Genes related to PAEs are obtained from the Comparative Toxicogenomics Database. We constructed polygenic scores for sex hormone-binding globulin (SHBG) and testosterone, and functional SNPs for IL-6, PPARG, and GPX1 from genotyping data, and further analyzed the environment-gene interactions. The positive associations of PAEs (DMP, DiBP, DnBP, DEHP) with mortality were only observed in males but not in females. Comparing with the extreme quartile 1, the HRs (95% CI) for quartile 4 were 1.63 (.17, 2.26) for DMP, 1.82 (1.29, 2.56) for DiBP, 1.68 (1.18, 2.40) for DnBP, 1.66 (1.17, 2.36) for DEHP. Enrichment analysis showed that PAEs-related genes were mainly associated with hormones and IL-6-related pathways. Genetic variants of SHBG, testosterone, and IL-6 modified the association between PAEs mixture and all-cause mortality. PAEs exposure are associated with all-cause mortality among diabetic cases, and PAE exposure increases the risk of all-cause mortality only in males. Effects on the hormonal system and IL6-related pathways may be potential mechanisms.

Prognostic Effect of Obstructive Sleep Apnea in Acute Coronary Syndrome Patients with Heart Failure.

BACKGROUND AND OBJECTIVE: Acute coronary syndrome (ACS), heart failure (HF) and obstructive sleep apnea (OSA) often overlap and interact, the impact of OSA on ACS patients with HF remains unclear. The study sought to comprehensively evaluate the effects of the interaction between OSA and HF on long-term cardiovascular outcomes in ACS patients. METHODS: Between June 2015 and January 2020, patients hospitalized for ACS were prospectively enrolled and underwent portable sleep monitoring after clinically stabilization. OSA was defined as an apnea hypopnea index ≥ 15 events/h. HF was defined using medical records. The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), including death, myocardial infarction, stroke, ischemia-driven revascularization, and hospitalization for unstable angina. RESULTS: Among all 1927 included patients, 214 (11.1%) had HF, and 1,014 (52.6%) had OSA. For 2.9 years (1.5, 3.6 years) follow-up, OSA was independently associated with the risk of MACCE in HF patients (adjusted hazard ratio [HR], 2.11; 95%CI, 1.16-3.84; P=0.014), but not in those without HF (adjusted HR, 1.15; 95%CI, 0.92-1.45; P=0.228). Further analysis showed OSA exerted more prognostic effect in HF patients with preserved eject fraction (adjusted HR, 2.45; 95% CI, 1.11-5.41; P=0.027) than those with reduced eject fraction (adjusted HR, 1.62; 95% CI, 0.63-4.20; P=0.319). CONCLUSIONS: In the settings of ACS, OSA was independently associated with poor prognosis in patients with concomitant HF especially those with persevered ejection fraction. Screening and treatment for OSA are highly recommended in ACS patients with HF. CLINICAL TRIAL REGISTRATION: URL: www.clinicaltrails.gov; Unique Identifier: NCT03362385.