Linking growth performance and carcass traits with enterotypes in Muscovy ducks.

Objective: Enterotypes (ETs) are the clustering of gut microbial community structures, which could serve as indicators of growth performance and carcass traits. However, ETs have been sparsely investigated in waterfowl. The objective of this study was to identify the ileal ETs and explore the correlation of the ETs with growth performance and carcass traits in Muscovy ducks. Methods: A total of 200 Muscovy ducks were randomly selected from a population of 5,000 ducks at 70-day old, weighed and slaughtered. The growth performance and carcass traits, including body weight, dressed weight and evidenced weight, dressed percentage, percentage of apparent yield, breast muscle weight, leg muscle weight, percentage of leg muscle and percentage of breast muscle, were determined. The contents of ileum were collected for the isolation of DNA and 16S rRNA gene sequencing. The ETs were identified based on the 16S rRNA gene sequencing data and the correlation of the ETs with growth performance and carcass traits was performed by Spearman correlation analysis. Results: Three ETs (ET1, ET2, and ET3) were observed in the ileal microbiota of Muscovy ducks with significant differences in number of features and α-diversity among these ETs (P < 0.05). Streptococcus, Candida Arthritis, and Bacteroidetes were the presentative genus in ET1 to ET3, respectively. Correlation analysis revealed that Lactococcus and Bradyrhizobium were significantly correlated with percentage of eviscerated yield and leg muscle weight (P < 0.05) while ETs were found to have a close association with percentage of eviscerated yield, leg muscle weight, and percentage of leg muscle in Muscovy ducks. However, the growth performance of ducks with different ETs did not show significant difference (P > 0.05). Lactococcus were found to be significantly correlated with leg muscle weight, dressed weight, and percentage of eviscerated yield. Conclusion: Our findings revealed a substantial variation in carcass traits associated with enterotypes in Muscovy ducks. It is implied that ETs might have the potential to serve as a valuable biomarker for assessing duck carcass traits. It would provide novel insights into the interaction of gut microbiota with growth performance and carcass traits of ducks.

Association between periodontal disease and coronary heart disease: A bibliometric analysis.

Background: Periodontal disease and coronary heart disease are both prevalent diseases worldwide and cause patients physical and mental suffering and a global burden. Recent studies have suggested a link between periodontal disease and coronary heart disease, but there is less research in this field from the perspective of bibliometrics. Objective: This study aimed to quantitatively analyze the literature on periodontal disease and coronary heart disease to summarize intellectual bases, research hotspots, and emerging trends and pave the way for future research. Methods: The Science Citation Index Expanded database was used to retrieve study records on periodontal disease and coronary heart disease from 1993 to 2022. After manual screening, the data were used for cooperative network analysis (including countries/regions, institutions and authors), keyword analysis, and reference co-citation analysis by CiteSpace software. Microsoft Excel 2019 was applied for curve fitting of annual trend in publications and citations. Results: A total of 580 studies were included in the analysis. The number of publications and citations in this field has shown an upward trend over the past 30 years. There was less direct collaboration among authors and institutions in this field but closer collaboration between countries. The United States was the country with the most published articles in this field (169/580, 29.14%). Based on the results of keyword analysis and literature co-citation analysis, C-reactive protein, oral flora, atherosclerosis, infection, and inflammation were previous research hotspots, while global burden and cardiovascular outcomes were considered emerging trends in this field. Conclusion: Studies on periodontal disease and coronary heart disease, which have attracted the attention of an increasing number of researchers, have been successfully analyzed using bibliometrics and visualization techniques. This paper will help scholars better understand the dynamic evolution of periodontal disease and coronary heart disease and point out the direction for future research. Clinical significance: This paper presents an overview between periodontal disease and coronary heart disease. Further exploration of the two diseases themselves and the potential causal relationship between the two is necessary and relevant, which may impact basic research, diagnosis, and treatment related to both diseases. This will aid the work of researchers and specialist doctors, and ultimately benefit patients with both diseases.

Clopidogrel with indobufen or aspirin in minor ischemic stroke or high-risk transient ischemic attack: a randomized controlled clinical study.

BACKGROUND: Ischemic stroke and transient ischemic attack (TIA) are the most prevalent cerebrovascular diseases. The conventional antiplatelet drugs are associated with an inherent bleeding risk, while indobufen is a new antiplatelet drug and has the similar mechanism of antiplatelet aggregation as aspirin with more safety profile. However, there have been no studies evaluating the combination therapy of indobufen and clopidogrel for antiplatelet therapy in cerebrovascular diseases. OBJECTIVE: The CARMIA study aims to investigate the effectiveness and safety of a new dual antiplatelet therapy consisting of indobufen and clopidogrel comparing with the conventional dual antiplatelet therapy consisting of aspirin and clopidogrel in patients with minor ischemic stroke or high-risk TIA. METHODS: An open-label randomized controlled clinical trial was conducted at a clinical center. We randomly assigned patients who had experienced a minor stroke or transient ischemic attack (TIA) within 72 h of onset, or within 1 month if they had intracranial stenosis (IS), to receive either indobufen 100 mg twice daily or aspirin 100 mg once daily for 21 days. For patients with IS, the treatment duration was extended to 3 months. All patients received a loading dose of 300 mg clopidogrel orally on the first day, followed by 75 mg once daily from the second day to 1 year. We collected prospective data using paper-based case report forms, and followed up on enrolled patients was conducted to assess the incidence of recurrent ischemic stroke or TIA, mRS score, NIHSS (National Institutes of Health Stroke Scale) score, and any bleeding events occurring within 3 month after onset. RESULTS: We enrolled 202 patients diagnosed with ischemic stroke or transient ischemic attack. After applying the criteria, 182 patients were eligible for data analysis. Endpoint events (recurrence of ischemic stroke/TIA, myocardial infarction, or death) were observed in 6 patients (6.5%) receiving aspirin and clopidogrel, including 4 (4.3%) with stroke recurrence, 1 (1.1%) with TIA recurrence, and 1 (1%) with death. In contrast, no endpoint events were reported in the indobufen and clopidogrel group (P = 0.029). The group of patients receiving indobufen and clopidogrel exhibited significantly lower modified Rankin Scale (mRS) score. (scores range from 0 to 6, with higher scores indicating more severe disability) compared to the aspirin and clopidogrel group (common odds ratio 3.629, 95% CI 1.874-7.036, P < 0.0001). Although the improvement rate of NIHSS score in the indobufen and clopidogrel group was higher than that in the aspirin and clopidogrel group, the difference was not statistically significant (P > 0.05). Bleeding events were observed in 8 patients (8.6%) receiving aspirin and clopidogrel, including 4 (4.3%) with skin bleeding, 2 (2.2%) with gingival bleeding, 1 (1.1%) with gastrointestinal bleeding, and 1 (1.1%) with urinary system bleeding. On the other hand, only 1 patient (1.1%) in the indobufen and clopidogrel group experienced skin bleeding (P = 0.035). CONCLUSION: The combination of indobufen and clopidogrel has shown non-inferior and potentially superior effectiveness and safety compared to aspirin combined with clopidogrel in patients with minor ischemic stroke and high-risk TIA in the CARMIA study (registered under chictr.org.cn with registration number ChiCTR2100043087 in 01/02/2021).

Preliminary investigation on the analysis of the whole components of Pogejiuxin decoction and its formulation pattern based on ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

RATIONAL: Pogejiuxin decoction (PGJXD) is one of the most important formulas for the treatment of heart failure. However, there is a great lack of research on the material basis of this formula, especially research on its compatibility laws, which restricts its clinical use. Studying the complete ingredients and compatibility rules of PGJXD has great significance for guiding clinical medication. METHODS: The entire formula, the major single herbs, the drug pairs and the disassembled formula were analyzed by ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC/QTOFMS/MS), matching the chemical composition database and global natural product social molecular networking to explain the chemical composition as well as the combination pattern of PGJXD. RESULTS: A total of 1048 chemical constituents were fully analyzed from the major single herbs, the drug pairs and the disassembled formula and 188 chemical constituents, including 13 potential novel compounds, were firstly identified from the whole formula. We found that the chemical compositions were reduced after the single herbs were matched to the other herbs, especially the significant reduction of highly toxic diester alkaloids after compatibility, indicating that the medicines of PGJXD were interdependent and controlled by each other. CONCLUSION: This study innovatively researches and compares the compositional differences between the entire formula of PGJXD, the single, paired and separated formulas, greatly extending our understanding of the chemical substance basis of these compounds, and preliminarily explores the compatibility laws of PGJXD, providing some theoretical guidance for clinical medication.

One-Shot Single-Cell Proteome and Metabolome Analysis Strategy for the Same Single Cell.

Characterizing the profiles of proteome and metabolome at the single-cell level is of great significance in single-cell multiomic studies. Herein, we proposed a novel strategy called one-shot single-cell proteome and metabolome analysis (scPMA) to acquire the proteome and metabolome information in a single-cell individual in one injection of LC-MS/MS analysis. Based on the scPMA strategy, a total workflow was developed to achieve the single-cell capture, nanoliter-scale sample pretreatment, one-shot LC injection and separation of the enzyme-digested peptides and metabolites, and dual-zone MS/MS detection for proteome and metabolome profiling. Benefiting from the scPMA strategy, we realized dual-omic analysis of single tumor cells, including A549, HeLa, and HepG2 cells with 816, 578, and 293 protein groups and 72, 91, and 148 metabolites quantified on average. A single-cell perspective experiment for investigating the doxorubicin-induced antitumor effects in both the proteome and metabolome aspects was also performed.

M2-type macrophage-targeted delivery of IKKß siRNA induces M2-to-M1 repolarization for CNV gene therapy.

Choroidal Neovascularization (CNV) is capable of inciting recurrent hemorrhage in the macular region, severely impairing patients' visual acuity. During the onset of CNV, infiltrating M2 macrophages play a crucial role in promoting angiogenesis. To control this disease, our study utilizes the RNA interference (RNAi)-based gene therapy to reprogram M2 macrophages to the M1 phenotype in CNV lesions. We synthesize the mannose-modified siRNA-loaded liposome specifically targeting M2 macrophages to inhibit the inhibitory kappa B kinase ß (IKKß) gene involved in the polarization of macrophages, consequently modulating macrophage polarization state. In vitro and in vivo, the mannose-modified IKKß siRNA-loaded liposome (siIKKß-ML) has been proven to effectively target M2 macrophages to repolarize them to M1 phenotype, and inhibit the progression of CNV. Collectively, our findings elucidate that siIKKß-ML holds the potential to control CNV by reprogramming the macrophage phenotype, indicating a promising therapeutic avenue for CNV management.

Medium-intensity statin with ezetimibe versus high-intensity statin in acute ischemic cerebrovascular disease (MESIA): A randomized clinical trial.

BACKGROUND: High-risk stroke patients are recommended to receive high-intensity statin therapy to reduce the risk of stroke recurrence. However, doubling the dosage of statin drugs did not increase the achievement rate of LDL-C target or provide additional clinical benefits, but significantly increased the risk of adverse reactions. Statins and ezetimibe work through different mechanisms and the combined use of statins and ezetimibe significantly improves outcomes with comparable safety profiles. We tested the hypothesis that moderate-intensity statin with ezetimibe may offer advantages over the conventional high-intensity statin regimen in terms of efficacy and safety. METHODS: We conducted a randomized controlled trial. Eligible participants were aged 18 years or older with acute ischemic cerebrovascular disease. We randomly assigned (1:1) participants within the acute phase of ischemic stroke, i.e., within 1 week after the onset of mild ischemic stroke (NIHSS score ≤ 5), within 1 month for severe cases (NIHSS score ≥ 16), and within 2 weeks for the rest, as well as patients with TIA within 1 week of symptom onset, to receive either moderate-intensity statin with ezetimibe (either 10-20 mg atorvastatin calcium tablets plus a 10 mg ezetimibe tablet, or 5-10 mg rosuvastatin calcium tablets once per day plus a 10 mg ezetimibe tablet once per day) or high-intensity statin (40 mg atorvastatin calcium tablets or 20 mg rosuvastatin calcium tablets once per day) for 3 months. Randomization was performed using a random number table method. The primary efficacy outcome was the level and achievement rate of LDL-C after 3 months of treatment, specifically LDL-C ≤ 1.8 mmol/L or a reduction in LDL-C ≥ 50 %. The secondary outcome was the incidence of new stroke or transient ischemic attack (TIA) within 3 months. The safety outcome was liver and renal function tests, and the occurrence of statin-related muscle events within 3 months. FINDINGS: This trial took place between March 15, 2022, and March 7, 2023. Among 382 patients screened, 150 patients were randomly assigned to receive either medium-intensity statins with ezetimibe (n = 75) or high-intensity statins (n = 75). Median age was 60.0 years (IQR 52.75-70.25); 49 (36.6 %) were women and 85 (63.4 %) were men. The target achievement of LDL-C at 3 months occurred in 62 (89.86 %) of 69 patients in the medium-intensity statin with ezetimibe group and 46 (70.77 %) of 65 patients in the high-intensity statin group (P=0.005, OR=0.273, 95 % CI: 0.106, 0.705). The reduction magnitude of LDL-C in moderate-intensity statin with ezetimibe group was significantly higher (-56.540 % vs -47.995 %, P=0.001). Moderate-intensity statin with ezetimibe group showing a trend of a greater reduction in LDL-C absolute value than high-intensity statin group but without statistical significance (-1.77±0.90 vs -1.50±0.89, P=0.077). New AIS or TIA within 3 months, liver and renal function tests, and the occurrence of statin-related muscle events within 3 months were also statistically insignificant. Multivariate logistic regression analysis showed that both gender and lipid-lowering regimen as independent risk factors influencing the rate of LDL-C achievement in individuals diagnosed with acute ischemic cerebrovascular disease, but only lipid-lowering regimen had predictive value. INTERPRETATION: Compared to guideline-recommended high-intensity statin therapy, moderate-intensity statin with ezetimibe further improved the achievement rate of LDL-C in patients with acute ischemic cerebrovascular disease, with a higher reduction magnitude in LDL-C. In terms of safety, there was no significant difference between the two regimens, suggesting that moderate-intensity statin with ezetimibe can also be considered as an initial treatment option for patients with acute ischemic cerebrovascular disease.

Mild hypothermia reduces lipopolysaccharide-induced microglial activation via down-regulation of Tent5c.

Microglial activation is a critical factor in the pathogenesis and progression of neuroinflammatory diseases. Mild hypothermia, known for its neuroprotective properties, has been shown to alleviate microglial activation. In this study, we explore the differentially expressed (DE) mRNAs and long non-coding RNAs (lncRNAs) in BV-2 microglial cells under different conditions: normal temperature (CN), mild hypothermia (YT), normal temperature with lipopolysaccharide (LPS), and mild hypothermia with LPS (LPS + YT). Venn analysis revealed 119 DE mRNAs that were down-regulated in the LPS + YT vs LPS comparison but up-regulated in the CN vs LPS comparison, primarily enriched in Gene Ontology terms related to immune and inflammatory responses. Furthermore, through Venn analysis of YT vs CN and LPS + YT vs LPS comparisons, we identified 178 DE mRNAs and 432 DE lncRNAs. Among these transcripts, we validated the expression of Tent5c at the protein and mRNA levels. Additionally, siRNA-knockdown of Tent5c attenuated the expression of pro-inflammatory genes (TNF-α, IL-1ß, Agrn, and Fpr2), cellular morphological changes, NLRP3 and p-P65 protein levels, immunofluorescence staining of p-P65 and number of cells with ASC-speck induced by LPS. Furthermore, Tent5c overexpression further potentiated the aforementioned indicators in the context of mild hypothermia with LPS treatment. Collectively, our findings highlight the significant role of Tent5c down-regulation in mediating the anti-inflammatory effects of mild hypothermia.

Tumor Exosomal ENPP1 Hydrolyzes cGAMP to Inhibit cGAS-STING Signaling.

To evade immune surveillance, tumor cells express ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) on the surface of their membrane, which degrades extracellular cyclic GMP-AMP (cGAMP), thereby inhibiting the cyclic GMP-AMP synthase (cGAS) stimulator of interferon gene (STING) DNA-sensing pathway. To fully understand this tumor stealth mechanism, it is essential to determine whether other forms of ENPP1 with hydrolytic cGAMP activity also are present in the tumor microenvironment to regulate this innate immune pathway. Herein, it is reported that various tumor-derived exosomes carry ENPP1, and can hydrolyze synthetic 2'3'-cGAMP and endogenous 2'3'-cGAMP produced by cells to inhibit cGAS-STING pathway in immune cells. Moreover, tumor exosomal ENPP1 also can hydrolyze 2'3'-cGAMP bound to LL-37 (an effective transporter of 2'3'-cGAMP) to inhibit STING signaling. Furthermore, high expression of ENPP1 in exosomes is observed isolated from human breast and lung cancer tissue, and tumor exosomal ENPP1 inhibited the immune infiltration of CD8+ T cells and CD4+ T cells. The results elucidate the essential function of tumor exosomal ENPP1 in the cGAS-STING pathway, furthering understanding of the crosstalk between the tumor cells and immune system.

Identification of renal ischemia reperfusion injury-characteristic genes, pathways and immunological micro-environment features through bioinformatics approaches.

BACKGROUND: Biomarkers and pathways associated with renal ischemia reperfusion injury (IRI) had not been well unveiled. This study was intended to investigate and summarize the regulatory networks for related hub genes. Besides, the immunological micro-environment features were evaluated and the correlations between immune cells and hub genes were also explored. METHODS: GSE98622 containing mouse samples with multiple IRI stages and controls was collected from the GEO database. Differentially expressed genes (DEGs) were recognized by the R package limma, and the GO and KEGG analyses were conducted by DAVID. Gene set variation analysis (GSVA) and weighted gene coexpression network analysis (WGCNA) had been implemented to uncover changed pathways and gene modules related to IRI. Besides the known pathways such as apoptosis pathway, metabolic pathway, and cell cycle pathways, some novel pathways were also discovered to be critical in IRI. A series of novel genes associated with IRI was also dug out. An IRI mouse model was constructed to validate the results. RESULTS: The well-known IRI marker genes (Kim1 and Lcn2) and novel hub genes (Hbegf, Serpine2, Apbb1ip, Trip13, Atf3, and Ncaph) had been proved by the quantitative real-time polymerase chain reaction (qRT-PCR). Thereafter, miRNAs targeted to the dysregulated genes were predicted and the miRNA-target network was constructed. Furthermore, the immune infiltration for these samples was predicted and the results showed that macrophages infiltrated to the injured kidney to affect the tissue repair or fibrosis. Hub genes were significantly positively or negatively correlated with the macrophage abundance indicating they played a crucial role in macrophage infiltration. CONCLUSIONS: Consequently, the pathways, hub genes, miRNAs, and the immune microenvironment may explain the mechanism of IRI and might be the potential targets for IRI treatments.

Pick-up single-cell proteomic analysis for quantifying up to 3000 proteins in a Mammalian cell.

The shotgun proteomic analysis is currently the most promising single-cell protein sequencing technology, however its identification level of ~1000 proteins per cell is still insufficient for practical applications. Here, we develop a pick-up single-cell proteomic analysis (PiSPA) workflow to achieve a deep identification capable of quantifying up to 3000 protein groups in a mammalian cell using the label-free quantitative method. The PiSPA workflow is specially established for single-cell samples mainly based on a nanoliter-scale microfluidic liquid handling robot, capable of achieving single-cell capture, pretreatment and injection under the pick-up operation strategy. Using this customized workflow with remarkable improvement in protein identification, 2449-3500, 2278-3257 and 1621-2904 protein groups are quantified in single A549 cells (n = 37), HeLa cells (n = 44) and U2OS cells (n = 27) under the DIA (MBR) mode, respectively. Benefiting from the flexible cell picking-up ability, we study HeLa cell migration at the single cell proteome level, demonstrating the potential in practical biological research from single-cell insight.

Evaluation of tear film in patients with AIDS without opportunistic ocular infections in the era of COVID-19: A case-control study.

PURPOSE: The assessment of tear film and ocular surface conditions in patients with acquired immunodeficiency syndrome (AIDS) has been poorly studied thus far. We aim to assess tear film parameters, ocular surface characteristics, and dry eye disease (DED) symptoms of patients with AIDS who did not undergo highly active antiretroviral treatment (HAART). METHODS: This case-control study included 154 age-, sex-, and ethnicity-matched healthy controls and patients with AIDS. All participants underwent comprehensive ocular surface assessment and subjective DED symptomology evaluation. Data were collected between March 2022 and July 2022. RESULTS: HAART-naïve patients with AIDS had a shorter noninvasive tear film breakup time (median 3.76 vs. 8.54 s), thinner tear film lipid layer thickness (median 73.00 vs. 91.00 nm), and lower Schirmer I test values (median 5.00 mm/5 min vs. 12.00 mm/5 min) (all P < 0.001). Moreover, higher corneal fluorescein staining scores (median 1.00 vs. 0.00) and higher upper, lower, and total meibomian gland grades were observed in AIDS patients (all P < 0.05). Negative correlations between the blood viral load and the Ocular Surface Disease Index score ( r = -3.50, P = 0.027) and the Schirmer I test score ( r = -0.374, P = 0.017) were detected in patients with AIDS. CONCLUSION: Altered tear film status was observed in individuals with HAART-naïve AIDS, even when there were no other ocular symptoms present. Therefore, patients with AIDS should be encouraged to undergo comprehensive ocular surface examinations to detect any subclinical tear film alterations occurring.

A Miniaturized Wireless Micropump Enabled by Confined Acoustic Streaming.

Miniaturization of health care, biomedical, and chemical systems is highly desirable for developing point-of-care testing (POCT) technologies. In system miniaturization, micropumps represent one of the major bottlenecks due to their undesirable pumping performance at such small sizes. Here, we developed a microelectromechanical system fabricated acoustic micropump based on an ultrahigh-frequency bulk acoustic wave resonator. The concept of an inner-boundary-confined acoustic jet was introduced to facilitate unidirectional flow. Benefitting from the high resonant frequency and confined acoustic streaming, the micropump reaches 32.620 kPa/cm3 (pressure/size) and 11.800 ml/min∙cm3 (flow rate/size), showing a 2-order-of-magnitude improvement in the energy transduction efficiency compared with the existing acoustic micropumps. As a proof of concept, the micropump was constructed as a wearable and wirelessly powered integrated drug delivery system with a size of only 9×9×9 mm3 and a weight of 1.16 g. It was demonstrated for ocular disease treatment through animal experimentation and a human pilot test. With superior pumping performance, miniaturized pump size, ultralow power consumption, and complementary metal-oxide-semiconductor compatibility, we expect it to be readily applied to various POCT applications including clinical diagnosis, prognosis, and drug delivery systems.

Biochemical Pathways of Salicylic Acid Derived from l-Phenylalanine in Plants with Different Basal SA Levels.

As a plant hormone, salicylic acid (SA) has diverse regulatory roles in plant growth and stress resistance. Although SA is widely found in plants, there is substantial variation in basal SA among species. Tea plant is an economically important crop containing high contents of SA whose synthesis pathway remains unidentified. The phenylalanine ammonia-lyase (PAL) pathway is responsible for basal SA synthesis in plants. In this study, isotopic tracing and enzymatic assay experiments were used to verify the SA synthesis pathway in tea plants and evaluate the variation in phenylalanine-derived SA formation among 11 plant species with different levels of SA. The results indicated that SA could be synthesized via PAL in tea plants and conversion efficiency from benzoic acid to SA might account for variation in basal SA among plant species. This research lays the foundation for an improved understanding of the molecular regulatory mechanism for SA biosynthesis.

Association of D-dimer to albumin ratio with adverse cardiovascular outcomes in ischaemic heart failure patients with diabetes mellitus: a retrospective cohort study.

OBJECTIVE: To determine the association of D-dimer to albumin ratio (DAR) with major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) in ischaemic heart failure patients with diabetes mellitus. DESIGN: A retrospective observational cohort study. SETTING: Single centre in Beijing, China, conducted at one of the largest cardiology centres in China. PARTICIPANTS: From June 2017 to June 2019, 3707 patients with heart failure and concomitant multiple vessel disease undergoing elective PCI were screened. A total 1021 of patients were enrolled after exclusion and the follow-up period was up to 36 months. PRIMARY AND SECONDARY OUTCOME MEASURES: The MACE was the primary measured outcome. The secondary outcomes were all-cause mortality, non-fatal myocardial infarction and any revascularisation. METHODS: These participants were grouped according to DAR tertiles. The cumulative incidence functions, Cox regression, restricted cubic spline and receiver operating characteristic curves were used to determine the association between DAR and outcomes. The subgroup analysis was also performed. RESULTS: After follow-up, MACE occurred in 404 (39.6%) participants. The cumulative hazards curve manifested significant differences in MACE, all-cause mortality and any revascularisation (log-rank test: all p<0.001). In adjusted models, DAR was an independent risk factor of MACE (tertile 2: HR 1.82, 95% CI 1.37 to 2.42; tertile 3: HR 1.74, 95% CI 1.28 to 2.36) and all-cause mortality (tertile 2: HR 2.04, 95% CI 1.35 to 3.11; tertile 3: HR 1.89, 95% CI 1.20 to 2.98). The optimal cut-off of DAR was 1.2. In the stratified analysis, sex, age, hypertension, hypercholesterolaemia, total revascularisation and any interfered vessel did not affect the independent predictive ability. CONCLUSION: Higher DAR was independently associated with MACE and all-cause mortality after PCI in ischaemic heart failure patients with diabetes mellitus.

Identification of Reduced mTOR T1262 Phosphorylation as a Novel Mechanism and Therapeutic Target of Apoptosis in Senescent Cardiomyocytes: Aging and Cardiomyocyte Apoptosis.

The mechanisms through which aging increases heart injury remain partially understood. Protein phosphorylation plays a critical regulatory role in cell survival and death. Using an unbiased phosphoproteomics approach, we aimed to identify the proteins whose phosphorylation could be causatively related to aging-related cardiomyocyte apoptosis and elucidate the underlying mechanisms. Comparative phosphoproteomics was conducted on cardiac tissues obtained from young (8 weeks) and aged (24 months) mice. Our findings revealed that the Mammalian Target of Rapamycin phosphorylation at T1262 (mTORT1262) was reduced in the aging heart. Immunohistochemical and Western blot analyses confirmed these findings in aging myocardia and D-galactose-induced senescent AC16 cardiomyocytes. In hypoxia/reoxygenation cardiomyocytes, mTORT1262 phosphorylation deficiency (mTORT1262A, lentivirus-mediated transfection) inhibited AKT1, suppressed NF-κB, activated FOXO1/3a signaling, and ultimately exacerbated apoptosis. Conversely, mTORT1262 pseudophosphorylation (mTORT1262E) exhibited opposite effects. Through bioinformatics and CO-IP, purinergic receptor P2X4 (P2X4R) was found to be the possible receptor responsible for mTORT1262 phosphorylation. Knockdown of P2X4R increased apoptosis, whereas its overexpression decreased it. In senescent cardiomyocytes, P2X4R expression and mTORT1262 and AKT1S473 phosphorylation were reduced, NF-κB signaling was suppressed, and FOXO1/3a signaling was activated. We demonstrated that P2X4R downregulation and the subsequent reduction of mTORT1262 phosphorylation is a novel mechanism contributing to cardiomyocyte apoptosis in aging hearts. The P2X4R-mTOR-AKT1 signaling pathway represents a potential therapeutic target against accelerated cardiac injury in aging.

AI/ML to Relationship Between Circadian Rhythm of Blood Pressure and Left Ventricular Hypertrophy in Patients with Hypertension.

Objective: The objective of this experiment was to investigate the relationship between the circadian rhythm of blood pressure and left ventricular hypertrophy (LVH) in patients with hypertension. Methods: A total of 500 hypertension patients with documented circadian rhythm of blood pressure were selected for this study. The researchers collected general patient data and fasting blood samples. The following parameters were measured within subgroups of hypertensive patients: age, sex ratio, BMI, fasting blood glucose, total cholesterol, triacylglycerol, HDL-C, LDL-C, duration of hypertension, antihypertensive drug usage, and statin intake. Results: The results of the study showed that LVH hypertension had a significantly higher proportion of grade 3 hypertension compared to non-LVH hypertension (P < .001). Additionally, LVH hypertension displayed higher mean systolic blood pressure levels over a 24-hour period (P = .002), during daytime (P = .029), and during nighttime (P < .001). The 24-hour pulse pressure (P < .001) and pulse pressure index (P = 0.001) were also significantly higher in patients with LVH hypertension. Furthermore, the rate of blood pressure decline at night was significantly lower in the LVH hypertension group compared to the control group (P < .001). B-type natriuretic peptide (BNP) levels (P = .034) and left ventricular mass index (LVMI) (P < .001) were significantly higher in patients with LVH hypertension compared to non-LVH patients. Conclusions: The findings of this study suggest a close association between hypertensive LVH and the weakening or disappearance of the circadian rhythm of blood pressure. It was also observed that the level of blood pressure classification and plasma BNP levels were increased in patients with LVH hypertension.

[Retracted] Effects of miR­138­5p and miR­204­5p on the migration and proliferation of gastric cancer cells by targeting EGFR.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that the numerous immunohistochemical images shown in Fig. 1D on p. 2626 exhibited a number of overlaps comparing among the data panels, such that data which were intended to show the results from differently performed experiments were likely to have been derived from a smaller number of original sources. A subsequent independent investigation of the data in this paper in the Editorial Office also revealed that certain of the cell migration and invasion assay data shown in Fig. 4A on p. 2629 were strikingly similar to data that had previously appeared in a couple of already published papers written by different authors at different research institutes.  Owing to the fact that the contentious data in Fig. 4 in the above article had already been published prior to its submission to Oncology Reports, in addition to the matter of several panels in Fig. 1D showing overlapping data, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 39: 2624-2634, 2018; DOI: 10.3892/or.2018.6389].

Prognostic Value of Platelet-to-Lymphocyte Ratio Combined with CHA2DS2-VASc Score for Nonvalvular Atrial Fibrillation Induced Cardiogenic Cerebral Embolism.

Aim: To determine the predictive significance of the platelet-to-lymphocyte ratio (PLR) combined with the CHA2DS2-VASc score for cardiogenic cerebral embolism (CCE) in patients with nonvalvular atrial fibrillation (NVAF). Methods: A total of 553 patients with NVAF were included in this retrospective study. The general data, PLR, CHA2DS2-VASc score and echocardiography indicators were compared. The risk factors for CCE and the predictive value of PLR and CHA2DS2-VASc were analyzed. Stratified analysis was performed based on the cut-off value. Least absolute shrinkage and selection operator (LASSO) regression analysis was utilized to build a model. The relationship between risk score and different anticoagulants was evaluated. Results: Multiple regression analysis showed hypertension (OR=3.95, 95% CI=2.12-7.35, p=1.40×10-5), diabetes mellitus (OR=2.95, 95% CI=1.57-5.58, p=7.65×10-4), PLR (OR=1.01, 95% CI=1.00-1.01, p<10-6), creatinine level (OR=1.01, 95% CI=1.00-1.02, p=7.44×10-3), left atrial diameter (LAD) (OR=1.90, 95% CI=1.13-3.19, p=1.51×10-2), ejection fraction (EF) (OR=0.93, 95% CI=0.87-0.98, p=8.06×10-3) and CHA2DS2-VASc score (OR=3.79, 95% CI=2.95-4.85, p<10-6) were independent risk factors for CCE. A one-way linear analysis also showed the above seven indexes were significantly correlated with CCE (F=56.4, p<10-6). The area under the receiver operating characteristic (ROC) curve of PLR and CHA2DS2-VASc score was 0.760 (95% CI:0.721-0.800), and 0.855 (95% CI: 0.824-0.886), respectively. Pearson correlation analysis showed that PLR was correlated with CHA2DS2-VASc score (r=0.331, p<10-6). Stratified analysis indicated there was a positive correlation between different risk group (p<10-6). Using the LASSO model, a composite indicator displayed differential power for distinguishing CCE with an AUC value of 0.884 (95% CI: 0.857-0.911). Patients with dabigatran and rivaroxaban exhibited higher risk score than those with warfarin (warfarin vs dabigatran, p=1.40×10-2; warfarin vs rivaroxaban p=3.00×10-3). Conclusion: PLR and CHA2DS2-VASc score are independent risk factors for CCE with NVAF, and the combination of the two indices can improve the prediction of CCE.