Control of grain size and weight by the RNA-binding protein EOG1 in rice and wheat.

Grain size is one of the important yield traits in crops. Understanding the molecular and genetic mechanisms of grain-size control is important for yield improvement. Here, we report that the enhancer of GS2AA (EOG1) encodes an RNA-binding protein, which can bind mRNAs of several grain-size genes and influence their abundance. The eog1-1 mutant produces large and heavy grains by promoting cell proliferation in the spikelet hull. OsGSK3 physically interacts with and phosphorylates EOG1, thereby influencing the stability of EOG1. Genetic analyses support that EOG1 and OsGSK3 share overlapped function in grain size and weight control but does so independently of GS2. Notably, genome editing of wheat homologs TaEOG1A/B/D causes large and heavy grains. Thus, our findings identify a genetic and molecular mechanism whereby the OsGSK3-EOG1 module regulates grain size and weight in rice, suggesting that this pathway has the potential for grain-size improvement in key crops.

Association between oxidative balance scores and all-cause and cardiovascular disease-related mortality in patients with type 2 diabetes: data from the national health and nutrition examination survey (2007-2018).

BACKGROUND: Oxidative Balance Scores (OBS) is composite measures that assess the balance between pro-oxidant and antioxidant factors in an individual's diet and lifestyle. Evidence on OBS and cardiovascular disease (CVD) in diabetic patients is scarce. This study investigates the potential association between OBS and CVD-prevalence and all-cause and CVD-related mortality in adult diabetic patients. METHODS: Participants were selected from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. OBS-related data collection was initiated by linking the National Death Index to determine mortality due to all-cause and cardiovascular disease until December 31, 2019. Weighted logistic regression analyses explored the relationship between OBS and CVD. In addition, multivariable Cox proportional risk regression models and Kaplan-Meier curves were used to determine the correlation between OBS and mortality, with time to event as the time variable, as well as to estimate hazard ratios (HR) and 95% confidence interval (CI). RESULTS: A total of 3491 participants were included in the final analysis. Weighted logistic regression analysis of the relationship between OBS and CVD prevalence found that higher OBS was not associated with CVD prevalence compared with lower levels after fully adjustment in model 3 (OR: 0.82, 95% CI: 0.51-1.31, P = 0.39). During 3,491 person-years of follow-up, 408 deaths were recorded, of which 105 deaths were attributed to CVD. In fully adjusted model 3, participants in the highest quartile of OBS had significant reductions in all-cause mortality of 53% [HR: 0.47, 95% CI: 0.29-0.77), Ptrend= 0.002] and in cardiovascular disease mortality of 78% [HR: 0.22, 95% CI: 0.08-0.56), Ptrend= 0.004], compared with the lowest quartile groups of OBS. The Kaplan-Meier analysis results showed that participants in the highest quartile of OBS had the lowest risk of all-cause and CVD-related mortality and were statistically different (P < 0.05). Subgroup analysis confirmed that P for interaction was significant only concerning the educational level attained and in individuals with a history of CKD (P < 0.05). CONCLUSIONS: Although OBS wasn't very useful for assessing CVD prevalence outcomes, higher OBS was significantly associated with lower all-cause and CVD-related mortality, suggesting that maintaining adequate OBS may reduce mortality in patients with DM.

Downregulation of stromal interaction molecule-1 is implicated in the age-associated vasoconstriction dysfunction of aorta, intrarenal, and coronary arteries.

The contractile function of vascular smooth muscle cells (VSMCs) typically undergoes significant changes with advancing age, leading to severe vascular aging-related diseases. The precise role and mechanism of stromal interaction molecule-1 (STIM1) in age-mediated Ca2+ signaling and vasocontraction remain unclear. The connection between STIM1 and age-related vascular dysfunction was investigated using a multi-myograph system, immunohistochemical analysis, protein blotting, and SA-ß-gal staining. Results showed that vasoconstrictor responses in the thoracic aorta, intrarenal artery, and coronary artery decreased with age. STIM1 knockdown in the intrarenal and coronary arteries reduced vascular tone in young mice, while no change was observed in the thoracic aorta. A significant reduction in vascular tone occurred in the STIM1 knockout group with nifedipine. In the thoracic aorta, vasoconstriction significantly decreased with age following the use of nifedipine and thapsigargin and almost disappeared after STIM1 knockdown. The proportion of senescent VSMCs increased significantly in aged mice and further increased in sm-STIM1 KO aged mice. Moreover, the expression of senescence markers p21, p16, and IL-6 significantly increased with age, with p21 expression further increased in the STIM1 knockdown aged group, but not p16 or IL-6. These findings indicate that different arteries exhibit distinct organ-specific features and that STIM1 downregulation may contribute to age-related vasoconstrictive dysfunction through activation of the p21 pathway.

Identification and expression analysis of the Xyloglucan transglycosylase/hydrolase (XTH) gene family under abiotic stress in oilseed (Brassica napus L.).

XTH genes are key genes that regulate the hydrolysis and recombination of XG components and plays role in the structure and composition of plant cell walls. Therefore, clarifying the changes that occur in XTHs during plant defense against abiotic stresses is informative for the study of the plant stress regulatory mechanism mediated by plant cell wall signals. XTH proteins in Arabidopsis thaliana was selected as the seed sequences in combination with its protein structural domains, 80 members of the BnXTH gene family were jointly identified from the whole genome of the Brassica napus ZS11, and analyzed for their encoded protein physicochemical properties, phylogenetic relationships, covariance relationships, and interoperating miRNAs. Based on the transcriptome data, the expression patterns of BnXTHs were analyzed in response to different abiotic stress treatments. The relative expression levels of some BnXTH genes under Al, alkali, salt, and drought treatments after 0, 6, 12 and 24 h were analyzed by using qRT-PCR to explore their roles in abiotic stress tolerance in B. napus. BnXTHs showed different expression patterns in response to different abiotic stress signals, indicating that the response mechanisms of oilseed rape against different abiotic stresses are also different. This paper provides a theoretical basis for clarifying the function and molecular genetic mechanism of the BnXTH gene family in abiotic stress tolerance in rapeseed.

Risk factors analysis and the establishment of nomogram prediction model for PICC-related venous thrombosis in patients with lymphoma: a double-center cohort-based case-control study.

Objective: The objective of this study is to examine the risk factors associated with the occurrence of PICC-Related Venous Thrombosis (PICC-RVTE) in individuals diagnosed with lymphoma, as well as to develop a predictive risk nomogram model. Methods: A total of 215 patients with lymphoma treated at Yunnan Provincial Tumor Hospital from January 2017 to December 2020 were retrospectively evaluated as the training cohort; 90 patients with lymphoma treated at the Department of Oncology of the First People's Hospital of Anning, Affiliated to Kunming University of Science and Technology during the January 2021 to September 2023 were evaluated as the validation cohort. Independent influencing factors were analyzed by logistic regression, a nomogram was developed and validated, and the model was evaluated using internal and external data cohorts for validation. Results: A total of 305 lymphoma patients were selected and 35 (11.48%) PICC-RVTE occurred, the median time was 13 days. The incidence within 1-2week was 65.71%. Multivariate analysis suggested that the activity amount, thrombosis history(within the last 12 months), ATIII, Total cholesterol and D-dimer levels were independently associated with PICC-RVTE, and a nomogram was constructed based on the multivariate analysis. ROC analysis indicated good discrimination in the training set (area under the curve [AUC] = 0.907, 95%CI:0.850-0.964) and the testing set (AUC = 0.896, 95%CI: 0.782-1.000) for the PICC-RVTE nomogram. The calibration curves showed good calibration abilities, and the decision curves indicated the clinical usefulness of the prediction nomograms. Conclusions: Patients should be advised to undergo color Doppler ultrasound system testing within two week after the implantation of a PICC catheter to detect PICC-RVTE at an early stage. The validated nomogram can be used to predict the risk of catheter-related thrombosis (CRT) in patients with lymphoma who received at least one chemotherapy after PICC catheterization, no bleeding tendency, no recent history of anticoagulant exposure and no severe heart, lung, renal insufficiency. This model has the potential to assist clinicians in formulating individualized treatment strategies for each patient.

A stable and flexible Au@Ag NPs/PVA SERS platform for thiram residue detection on rough surface.

Flexible and transparent surface-enhanced Raman scattering (SERS) substrates have gained great attention in analysis field as they offer a fast, non-destructive, and highly sensitive platform for in-situ detection. In this work, we present a facile one-pot strategy for synthesizing gold-cored silver shell nanoparticles (Au@Ag NPs) in the polyvinyl alcohol (PVA) colloid. With no other reducing agents, PVA can serve as both reducing and stabilizing agents for forming Au@Ag NPs. Besides, PVA acts as a scaffold to maintain SERS "hot-spots" by preventing nanoparticle aggregation. By using this flexible Au@Ag NPs/PVA colloid, the analytes can be extracted from rough surfaces for SERS measurements with excellent sensitivity, repeatability and stability. The SERS activity of the Au@Ag NPs/PVA remained at 89.8% even after 120 days of storage at room temperature in sealed air atmosphere. The selective detection of thiram residues on the surface of fruits and vegetables was successfully achieved. The limits of detection for thiram residues on apple and tomato surfaces were measured to be 0.58 and 0.56 ng cm-2, respectively, with recovery rate ranging from 91% to 107%. This work demonstrates the immense application potential of SERS colloid platform in the fields of food safety and environmental analysis.

Overexpression of BnMYBL2-1 improves plant drought tolerance via the ABA-dependent pathway.

Drought stress is a major environmental challenge that poses considerable threats to crop survival and growth. Previous research has indicated anthocyanins play a crucial role in alleviating oxidative damage, photoprotection, membrane stabilization, and water retention under drought stress. However, the presence of MYBL2 (MYELOBBLASTOSIS LIKE 2), an R3-MYB transcription factor (TF) which known to suppress anthocyanin biosynthesis. In this study, four BnMYBL2 members were cloned from Brassica napus L, and BnMYBL2-1 was overexpressed in Triticum aestivum L (No BnMYBL2 homologous gene was detected in wheat). Subsequently, the transgenic wheat lines were treated with drought, ABA and anthocyanin. Results showed that transgenic lines exhibited greater drought tolerance compared to the wild-type (WT), characterized by improved leaf water content (LWC), elevated levels of soluble sugars and chlorophyll, and increased antioxidant enzyme activity. Notably, transgenic lines also exhibited significant upregulation in abscisic acid (ABA) content, along with the transcriptional levels of key enzymes involved in ABA signalling under drought. Results also demonstrated that BnMYBL2-1 promoted the accumulation of ABA and anthocyanins in wheat. Overall, the study highlights the positive role of BnMYBL2-1 in enhancing crop drought tolerance through ABA signalling and establishes its close association with anthocyanin biosynthesis. These findings offer valuable insights for the development of drought-resistant crop varieties and enhance the understanding of the molecular mechanisms underlying plant responses to drought stress.

Performance Optimization of Pb0.97La0.03Sc0.45Ta0.45Ti0.1O3 Ceramics by Annealing Process.

The annealing effects on Pb0.97La0.03Sc0.45Ta0.45Ti0.1O3 (PLSTT) ceramics prepared by the solid-state reaction method are systemically investigated using experimental and theoretical techniques. Comprehensive studies are performed on the PLSTT samples by varying annealing time (AT) from t (=0, 10, 20, 30, 40, 50 and 60) h. The properties involving ferroelectric polarization (FP), electrocaloric (EC) effect, energy harvesting performance (EHP) and energy storage performance (ESP) are reported, compared and contrasted. All these features are seen to gradually improve with the increase in AT, and they all reach the climaxed-shaped values and then decrease by further increasing the AT. For t = 40 h, the maximum FP (23.2 µC/cm2) is attained at an electric field of 50 kV/cm, while the high EHP effects (0.297 J/cm3) and positive EC are achieved (for ΔT~0.92 K and ΔS~0.92 J/(K·kg)) at 45 kV/cm. The EHP value of the PLSTT ceramics increased by 21.7% while the polarization value was enhanced by 33.3%. At t = 30 h, the ceramics have attained the best ESP value of 0.468 J/cm3 with an energy loss of 0.05 J/cm3. We strongly believe that the AT plays a crucial role in the optimization of different traits of the PLSTT ceramics.

Clinical Characteristics and Outcomes of Chinese Patients with Premature Acute Coronary Syndrome.

This study aimed to investigate the clinical characteristics and major adverse cardiovascular events (MACEs) of Chinese patients with premature acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). This study was a secondary retrospective analysis involving 2114 ACS patients undergoing PCI at a single center in China. The patients were divided into two groups according to age (premature ACS group: ≤ 55 years in men, ≤ 65 years in women; nonpremature ACS group: > 55 years in men, > 65 years in women). The primary endpoint was all-cause death, and the secondary endpoint was a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, target vessel revascularization, and recurrent angina at follow-up, defined as MACEs. The incidence of all-cause death and MACEs was significantly lower in the premature than in the nonpremature ACS group (P < 0.001). Female sex, higher triglyceride levels, and higher low-density lipoprotein cholesterol levels were identified as independent risk factors that accelerated the development of ACS, whereas higher high-density lipoprotein cholesterol levels were identified as protective factors. Furthermore, in patients with premature ACS, non-ST-elevation ACS, cardiac insufficiency, multivessel disease, and left main lesion were risk factors for MACEs. Younger individuals, especially females, are advised to undergo early screening for the risk factors of premature ACS. Primary prevention of dyslipidemia should be more aggressively promoted at a young age. For premature ACS patients undergoing PCI, strengthened management and regular re-examinations are necessary to avoid adverse cardiovascular events as much as possible.

Sophocarpine Alleviates Isoproterenol-Induced Kidney Injury by Suppressing Inflammation, Apoptosis, Oxidative Stress and Fibrosis.

One of the most common diseases affecting people and leading to high morbidity is kidney injury. The alleviation of inflammation and apoptosis is considered a potential therapeutic approach for kidney injury. Sophocarpine (SOP), a tetracyclic quinolizidine alkaloid, exhibits various beneficial biological properties. To investigate the effects of SOP on isoproterenol (ISO)-induced kidney injury, we randomly divided mice into four groups: Control, ISO, ISO+SOP (20 mg/kg) and ISO+SOP (40 mg/kg). SOP was administered intraperitoneally to the mice over two weeks, accompanied by intraperitoneal stimulation of ISO (10 mg/kg) for another four weeks. After the mice were sacrificed, several methods such as ELISA, staining (H&E, TUNEL, DHE and Masson) and Western blotting were applied to detect the corresponding indicators. The kidney injury serum biomarkers SCr and BUN increased after the ISO challenge, while this effect was reversed by treatment with SOP. Pathological changes induced by ISO were also reversed by treatment with SOP in the staining. The inflammatory cytokines IL-ß, IL-6, TNF-α, MCP-1 and NLRP3 increased after the challenge with ISO, while they were decreased by treatment with SOP. The apoptotic proteins cleaved-caspase-3 and Bax increased, while Bcl-2 decreased, after the challenge with ISO, and these effects were reversed by treatment with SOP. The antioxidant proteins SOD-1 and SOD-2 decreased after being stimulated by ISO, while they increased after the treatment with SOP. The fibrotic proteins collagen I, collagen III, α-SMA, fibronectin, MMP-2 and MMP-9 increased after the challenge with ISO, while they decreased after the treatment with SOP. We further discovered that the TLR-4/NF-κB and TGF-ß1/Smad3 signaling pathways were suppressed, while the Nrf2/HO-1 signaling pathway was activated. In summary, SOP could alleviate ISO-induced kidney injury by inhibiting inflammation, apoptosis, oxidative stress and fibrosis. The molecular mechanisms were suppression of the TLR-4/NF-κB and TGF-ß1/Smad3 signaling pathways and activation of the Nrf2/HO-1 signaling pathway, indicating that SOP might serve as a novel therapeutic strategy for kidney injury.

Interpretation for Individual Brain Age Prediction Based on Gray Matter Volume.

The relationship between age and the central nervous system (CNS) in humans has been a classical issue that has aroused extensive attention. Especially for individuals, it is of far greater importance to clarify the mechanisms between CNS and age. The primary goal of existing methods is to use MR images to derive high-accuracy predictions for age or degenerative diseases. However, the associated mechanisms between the images and the age have rarely been investigated. In this paper, we address the correlation between gray matter volume (GMV) and age, both in terms of gray matter themselves and their interaction network, using interpretable machine learning models for individuals. Our goal is not only to predict age accurately but more importantly, to explore the relationship between GMV and age. In addition to targeting each individual, we also investigate the dynamic properties of gray matter and their interaction network with individual age. The results show that the mean absolute error (MAE) of age prediction is 7.95 years. More notably, specific locations of gray matter and their interactions play different roles in age, and these roles change dynamically with age. The proposed method is a data-driven approach, which provides a new way to study aging mechanisms and even to diagnose degenerative brain diseases.

Study on exogenous application of thidiazuron on seed size of Brassica napus L.

Thidiazuron (TDZ) is a novel and efficient cytokinin commonly used in tissue culture, and numerous studies have demonstrated that TDZ can increase berry size. However, no study to date has explored the effect of TDZ on seed size of Brassica napus and the mechanism. To shed light on the effect of TDZ on the seed size of B. napus, four different concentrations of TDZ were applied to B. napus. Results indicated that TDZ treatment could increase the seed diameter and silique length of B. napus to varying degrees and 100 and 200 µmol/L TDZ treatments were the most effective with a 3.6 and 4.6% increase in seed diameter, respectively. In addition, the yield of B. napus was also substantially increased under TDZ treatment. On the other hand, confocal micrographs of embryos and cotyledon cells suggested that embryos and their cotyledon epidermal cells treated with 200 µmol/L TDZ were obviously larger in size than the control. Furthermore, TDZ promoted the upregulation of some key maternal tissue growth-related genes, including two G-protein signaling genes (AGG3 and RGA1) and two transcriptional regulators (ANT and GS2). The expression analysis of genes related to the auxin metabolic pathways, G-protein signaling, endosperm growth and transcriptional regulators confirmed that treatment with TDZ negatively regulated the key genes ABI5, AGB1, AP2, ARF2, and ARF18 during bud development stage and florescence. The results strongly suggested that TDZ might regulate the transcriptional levels of key genes involved in auxin metabolic pathways, G-protein signaling, endosperm growth and transcriptional regulators, which resulted in bigger cotyledon epidermal cells and seed size in B. napus. This study explored the mechanism of TDZ treatment on the seed size of B. napus and provided an important reference for improving rapeseed yield.

Observation of Vector Spin Seebeck Effect in a Noncollinear Antiferromagnet.

Spintronic phenomena to date have been established in magnets with collinear moments, where the spin injection through the spin Seebeck effect (SSE) is always along the out-of-plane direction. Here, we report the observation of a vector SSE in a noncollinear antiferromagnet (AF) LuFeO_{3}, where temperature gradient along the out-of-plane and also the in-plane directions can both inject a pure spin current and generate a voltage in the heavy metal via the inverse spin Hall effect (ISHE). We show that the thermovoltages are due to the magnetization from canted spins in LuFeO_{3}. Furthermore, in contrast to the challenges of generating, manipulating, and detecting spin current in collinear AFs, the vector SSE in LuFeO_{3} is readily viable in zero magnetic field and can be controlled by a small magnetic field of about 150 Oe at room temperature. The noncollinear AFs expand new realms for exploring spin phenomena and provide a new route to low-field antiferromagnetic spin caloritronics and magnonics.

Anxiety is associated with higher blood pressure rise induced by cuff inflation.

SUBJECTS: To assess whether anxiety is associated with a higher rise of blood pressure induced by cuff inflation. METHODS: At first, intro-aortic blood pressure was continuously record before cuff inflation as baseline value in 234 patients underwent coronary angiography, then the cuff was inflated to 200 mmHg and the intro-aortic blood pressure was record again as cuff inflation blood pressure. According to anxiety score, the patients were divided into anxiety group, subanxiety group, and nonanxiety group. The difference between the baseline blood pressure and the cuff inflation blood pressure was calculated as cuff inflation-induced blood pressure elevation. When the difference ≥10 mmHg, cuff inflation-induced blood pressure elevation was diagnosed. RESULTS: The cuff inflation systolic blood pressure (134.9 ± 22.4 versus 131.6 ± 22.3 mmHg, P < 0.01) and diastolic blood pressure (80.5 ± 11.9 versus 78.4 ± 11.6 mmHg, P < 0.01) were significantly higher than the baseline values, thus the mean cuff inflation-induced blood pressure elevation on systolic blood pressure was 3.3 ± 4.7 mmHg and that on diastolic blood pressure was 2.1 ± 4.9 mmHg. The anxiety subgroup had significantly higher percentage increase-systolic blood pressure and percentage increase-diastolic blood pressure levels (4.5 ± 3.1% and 5.6 ± 6.3%) than the nonanxiety subgroup (1.9 ± 3.3% and 2.0 ± 6.5%), meanwhile these values in the subanxiety subgroup were higher (3.2 ± 4.1% and 3.4 ± 5.7%) than the nonanxiety subgroup. CONCLUSION: Cuff inflation can induce a transient rise of intro-aortic blood pressure. Anxiety is associated with higher cuff inflation-induced blood pressure elevation.

Different impact factors for accurate oscillometric blood pressure measurement between sinus rhythm and atrial fibrillation.

This study was conducted to evaluate whether the impact factor on the accuracy of oscillometric blood pressure (BP) is different between the patients with atrial affiliation (AF) and sinus rhythm (SR). This study included 124 AF patients and 98 SR patients who underwent coronary arteriography. Upper arm oscillometric and intro-aortic BP were simultaneously measured three times, and the averages were recorded as final values, respectively. The difference between oscillometric and intro-aortic BP was recorded as delta BP. For reducing the influence of baseline BP on delta BP, a percentage difference (PD-BP) was calculated with the formula: PD-BP = delta BP/intro-aortic BP × 100%. The oscillometric SBP and DBP levels slightly underestimated intro-aortic BP (by 2.2/1.6 mmHg) in the SR group, but significantly underestimated (by 5.8/4.8 mmHg) in the AF group. Age was negatively correlated with delta SBP and positively with delta DBP in SR patients, but not correlated in AF patients. Otherwise, ventricular rate (VR) was negatively correlated with delta SBP or delta DBP in AF, which indicated that the accuracy of oscillometric BP declined as the VR increased. With intro-aortic BP as reference, the accuracy of oscillometric BP in AF patients is lower than SR patients. Meanwhile, age may impact the oscillometric BP accuracy in SR patients, but VR may impact that in AF patients.

The changes of the peripheral CD4+ lymphocytes and inflammatory cytokines in Patients with COVID-19.

To investigate the clinical value of changes in the subtypes of peripheral blood lymphocytes and levels of inflammatory cytokines in patients with COVID-19, the total numbers of lymphocytes and CD4+ lymphocytes and the ratio of CD4+/CD8+ lymphocytes were calculated and observed in different groups of patients with COVID-19. The results show that the lymphocytopenia in patients with COVID-19 was mainly manifested by decreases in the CD4+ T lymphocyte number and the CD4+/CD8+ ratio. The decreased number of CD4+ T lymphocytes and the elevated levels of TNF-α and IL-6 were correlated with the severity of COVID-19 disease.

Large Anomalous Nernst Effect in a van der Waals Ferromagnet Fe3GeTe2.

Anomalous Nernst effect, a result of charge current driven by temperature gradient, provides a probe of the topological nature of materials due to its sensitivity to the Berry curvature near the Fermi level. Fe3GeTe2, one important member of the recently discovered two-dimensional van der Waals magnetic materials, offers a unique platform for anomalous Nernst effect because of its metallic and topological nature. Here, we report the observation of large anomalous Nernst effect in Fe3GeTe2. The anomalous Hall angle and anomalous Nernst angle are about 0.07 and 0.09, respectively, far larger than those in common ferromagnets. By utilizing the Mott relation, these large angles indicate a large Berry curvature near the Fermi level, consistent with the recent proposal for Fe3GeTe2 as a topological nodal line semimetal candidate. Our work provides evidence of Fe3GeTe2 as a topological ferromagnet and demonstrates the feasibility of using two-dimensional magnetic materials and their band topology for spin caloritronics applications.

Real-World Relationship Between Proton Pump Inhibitors and Cerebro-Cardiovascular Outcomes Independent of Clopidogrel.

Previous studies have provided established evidence on adverse outcomes of the coadministration of proton pump inhibitors (PPIs) and clopidogrel, whereas cerebro-cardiovascular outcomes of PPI use in the absence of clopidogrel therapy remain controversial.In this study, we aimed to assess the association between PPIs and cerebro-cardiovascular outcomes independent of clopidogrel.Systematic searches were conducted in the Cochrane Library, PubMed, and Embase databases for all relevant studies up to August 2018. Odds ratios (ORs) with its 95% confidence intervals (CIs) were abstracted and pooled using the random-effects model.A total of 14 observational studies (13 cohort studies and 1 case-control study) were identified. Compared with non-PPI users, PPI users experienced higher risks of stroke (OR: 1.22, 95% CI: 1.08-1.36), myocardial infarction (MI; OR: 1.23, 95% CI: 1.14-1.32), cardiovascular death (OR: 1.83, 95% CI: 1.69-1.98), and major adverse cardiovascular events (MACEs; OR: 1.22, 95% CI: 1.05-1.40) independent of clopidogrel use, but not all-cause death (OR: 1.50, 95% CI: 0.99-2.25). In the subgroup analysis, PPI alone was associated with significant risks of new-onset MI (OR: 1.23, 95% CI: 1.13-1.35) and stroke (OR: 1.17, 95% CI: 1.05-1.30) in patients without previous MI or stoke and recurrent MI (OR: 1.24, 95% CI: 1.02-1.51) and stroke (OR: 1.36, 95% CI: 1.19-1.55) risks in patients with a previous MI.Based on current publications, PPI use seems to be associated with increased risks of stroke, MI, cardiovascular death, and MACEs independent of clopidogrel. Greater caution should be therefore exercised while considering its clinical benefits and further investigate any causal relationships.