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Abstract The investigation of triggers causing the onset and intensification of Northern Hemisphere Glaciation (NHG) during the late Pliocene is essential for understanding the global climate system, with important implications for projecting future climate changes. Despite their critical roles in the global climate system, influences of land-ocean interactions on high-latitude ice sheets remain largely unexplored. Here, we present a high-resolution Asian dust record from Ocean Drilling Program Site 1208 in the North Pacific, which lies along the main route of the westerlies. Our data indicate that atmosphere-land-ocean interactions affected aeolian dust emissions through modulating moisture and vegetation in dust source regions, highlighting a critical role of terrestrial systems in initiating the NHG as early as 3.6 Myr ago. Combined with additional multi-proxy and model results, we further show that westerly wind strength was enhanced, mainly at low-to-middle tropospheric levels, during major glacial events at about 3.3 and 2.7 Myr ago. We suggest that coupled responses of Earth’s surface dynamics and atmospheric circulation in the Plio-Pleistocene likely involved feedbacks related to changes in paleogeography, ocean circulation, and global climate.

Abstract The envelope (E) protein of the Japanese encephalitis virus (JEV) is a key protein for virus infection and adsorption of host cells, which determines the virulence of the virus and regulates the intensity of inflammatory response. The mutation of multiple aa residues in the E protein plays a critical role in the attenuated strain of JEV. This study demonstrated that the Asp to Gly, Ser, and His mutation of the E389 site, respectively, the replication ability of the viruses in cells was significantly reduced, and the viral neuroinvasiveness was attenuated to different degrees. Among them, the mutation at E389 site enhanced the E protein flexibility contributed to the attenuation of neuroinvasiveness. In contrast, less flexibility of E protein enhanced the neuroinvasiveness of the strain. Our results indicate that the mechanism of attenuation of E389 aa mutation attenuates neuroinvasiveness is related to increased flexibility of the E protein. In addition, the increased flexibility of E protein enhanced the viral sensitivity to heparin inhibition in vitro, which may lead to a decrease in the viral load entering brain. These results suggest that E389 residue is a potential site affecting JEV virulence, and the flexibility of the E protein of aa at this site plays an important role in the determination of neuroinvasiveness.

Abstract The mid-Piacenzian warm period (MPWP, ~3.264–3.025 Ma) has gained widespread interest due to its partial analogy with future climate. However, quantitative data–model comparison of East Asian Summer Monsoon (EASM) precipitation during the MPWP is relatively rare, especially due to problems in decoding the imprint of physical processes to climate signals in the records. In this study, pollen-based precipitation records are reconstructed and compared to the multi-model ensemble mean of the Pliocene Model Intercomparison Project Phase 2 (PlioMIP2). We find spatially consistent precipitation increase in most simulations but a spatially divergent change in MPWP records. We reconcile proxy data and simulation by decomposing physical processes that control precipitation. Our results 1) reveal thermodynamic control of an overall enhancement of EASM precipitation and 2) highlight a distinct control of thermodynamic and dynamical processes on increases of tropical and subtropical EASM precipitation, reflecting the two pathways of water vapor supply that enhance EASM precipitation, respectively.

Abstract Background Acute myocardial infarction (AMI) is characterized by inflammation, oxidative stress, and atherosclerosis, contributing to increased mortality risk. High-density lipoprotein (HDL) takes a crucial part in mitigating atherosclerosis and inflammation through its diverse functionalities. Conversely, fibrinogen is implicated in the development of atherosclerotic plaques. However, the mortality risk predictive capacity of fibrinogen to HDL-cholesterol ratio (FHR) in AMI patients remains unexplored. This research aimed to evaluate the effectiveness of FHR for mortality risk prediction in relation to AMI. Methods A retrospective study involving 13,221 AMI patients from the Cardiorenal ImprovemeNt II cohort (NCT05050877) was conducted. Baseline FHR levels were used to categorize patients into quartiles. The assessment of survival disparities among various groups was conducted by employing Kaplan‒Meier diagram. Cox regression was performed for investigating the correlation between FHR and adverse clinical outcomes, while the Fine-Gray model was applied to evaluate the subdistribution hazard ratios for cardiovascular death. Results Over a median follow-up of 4.66 years, 2309 patients experienced all-cause death, with 1007 deaths attributed to cardiovascular disease (CVD). The hazard ratio (HR) and its 95% confidence interval (CI) for cardiac and all-cause death among individuals in the top quartile of FHR were 2.70 (1.99–3.65) and 1.48 (1.26–1.75), respectively, in comparison to ones in the first quartile, after covariate adjustment. Restricted cubic spline analysis revealed that FHR was linearly correlated with all-cause mortality, irrespective of whether models were adjusted or unadjusted (all P for nonlinearity > 0.05). Conclusion AMI patients with increased baseline FHR values had higher all-cause and cardiovascular mortality, regardless of established CVD risk factors. FHR holds promise as a valuable tool for evaluating mortality risk in AMI patients. Trial registration The Cardiorenal ImprovemeNt II registry NCT05050877.

Wind power, as a pivotal technology in the fight against climate change and the advancement of sustainable energy, occupies an essential role in the global shift towards a new energy paradigm. However, the inherent fluctuation and episodic nature of wind power output pose formidable challenges to achieving precise forecasts, thereby impeding the accuracy of traditional forecasting methodologies. To address this, the paper introduces a novel forecasting approach, the VMD-IMPA-BiLSTM method. This method begins by applying the VMD technique to decompose wind power output into several sub-sequences, significantly reducing data non-stationarity and thus mitigating the negative impact of data volatility on forecasting accuracy. The IMPA method, an improvement over the traditional MPA, incorporates a Tent chaotic mapping for population initialization and a priority selection strategy based on average fitness, enhancing the model’s ability to perform global searches and local optimizations. Moreover, the IMPA is leveraged to optimize critical parameters of the BiLSTM, such as maximum training iterations, hidden layer units, and learning rate, thereby curtailing the subjectivity inherent in manual tuning and bolstering the model’s forecasting robustness. A thorough comparative analysis with other models has been conducted to evaluate the performance of the developed VMD-IMPA-BiLSTM forecasting model comprehensively. Simulation results indicate that the proposed method significantly outperforms the benchmark models in terms of prediction accuracy across various application scenarios, showcasing not only exceptional stability in forecasts but also a robust generalization capability across diverse contexts.

BackgroundThe Oxidative Balance Score (OBS), which quantifies the balance between antioxidants and pro-oxidants influenced by diet and lifestyle, is crucial given oxidative stress’s significant role in Chronic Kidney Disease (CKD). This study aims to determine the association between OBS and CKD using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018.MethodsWe analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018. OBS was constructed from a detailed array of 20 factors, including dietary nutrients and lifestyle behaviors. The relationship between OBS and CKD risk was evaluated using weighted logistic regression models, adjusted for potential confounders, with a generalized additive model (GAM) examining non-linear associations. Subgroup analyses and interaction effects across diverse demographic and clinical groups, along with sensitivity analyses, were performed to validate the findings.ResultsAmong 32,120 participants analyzed, 4,786 were identified with CKD. Fully adjusted weighted logistic regression analysis revealed that each unit increase in OBS was associated with a 2% reduction in CKD prevalence [OR: 0.98 (0.98–0.99), P < 0.001]. Higher OBS quartiles were significantly correlated with a decreased CKD risk [Q4 vs. Q1: OR: 0.82 (0.68–0.98), P = 0.03; P for trend = 0.01]. The GAM and smoothed curve fit indicated a linear relationship between OBS and the risk of CKD. Stratified and sensitivity analyses further substantiated the inverse relationship between OBS and CKD prevalence.ConclusionsOur findings from the NHANES data affirm a significant inverse association between OBS and CKD risk in the U.S. population, underscoring the role of optimizing dietary and lifestyle factors in managing CKD risk. These results advocate for incorporating OBS considerations into CKD prevention and treatment strategies.

Abstract Background Lipids are critical in bone metabolism, and several studies have highlighted their importance. This study aimed to investigate the relationship between apolipoprotein B (apo B) and bone mineral density (BMD) at different skeletal sites (lumbar spine, femoral neck, and total femur) and to compare the influence of apo B with other traditional lipid markers. Methods The study included participants from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2016 who had complete data for apo B and BMD at the three skeletal sites. We used weighted multivariate regression analysis, subgroup analysis, and interaction tests to examine associations. Restricted cubic spline (RCS) was used to examine the non-linear relationship. Results A total of 4,258 adults were included in the study. Multivariate linear regression analysis showed that the relationship between apo B and BMD varied by skeletal site: a negative association was found with lumbar spine BMD [β = -0.054, 95%CI: (-0.073, -0.035)]. In contrast, a positive association was found with femoral neck BMD [β = 0.031, 95%CI: (0.011, 0.051)] and no significant association between apo B and total femur BMD. Conclusions Our findings suggest that apo B is associated with BMD in a site-specific manner.

Abstract Background Globally, coronary artery disease (CAD) and cancer are the leading causes of death. Studies focusing on the proportion and spectrum of cancer mortality among CAD patients are lacking. We aim to characterize the proportion and spectrum of cancer‐specific mortality among patients with CAD. Methods We analyzed 93,797 hospitalized survivors with angiographically documented CAD between 2007 and 2020 (mean age: 62.8 ± 11.1 years, 24.7% female) from Cardiorenal ImprovemeNt II (CIN‐II) cohort. Results During the median follow‐up of 4.8 years (IQR: 2.6–7.5), 13,162 (14.0%) patients died after discharge. A total of 1223/7703 (15.8% of cause‐specific death) CAD patients died of cancer. The three most common types of cancer‐specific death were lung (36.1%), liver (13.3%), and colorectum cancer (12.8%). Furthermore, male (adjusted HR 2.38, 95% CI: 1.99–2.85) and older (≥60 vs.

Abstract Background Among patients with acute coronary syndrome and percutaneous coronary intervention, stress hyperglycemia ratio (SHR) is primarily associated with short-term unfavorable outcomes. However, the relationship between SHR and long-term worsen prognosis in acute myocardial infarction (AMI) patients admitted in intensive care unit (ICU) are not fully investigated, especially in those with different ethnicity. This study aimed to clarify the association of SHR with all-cause mortality in critical AMI patients from American and Chinese cohorts. Methods Overall 4,337 AMI patients with their first ICU admission from the American Medical Information Mart for Intensive Care (MIMIC)-IV database (n = 2,166) and Chinese multicenter registry cohort Cardiorenal ImprovemeNt II (CIN-II, n = 2,171) were included in this study. The patients were divided into 4 groups based on quantiles of SHR in both two cohorts. Results The total mortality was 23.8% (maximum follow-up time: 12.1 years) in American MIMIC-IV and 29.1% (maximum follow-up time: 14.1 years) in Chinese CIN-II. In MIMIC-IV cohort, patients with SHR of quartile 4 had higher risk of 1-year (adjusted hazard radio [aHR] = 1.87; 95% CI: 1.40–2.50) and long-term (aHR = 1.63; 95% CI: 1.27–2.09) all-cause mortality than quartile 2 (as reference). Similar results were observed in CIN-II cohort (1-year mortality: aHR = 1.44; 95%CI: 1.03–2.02; long-term mortality: aHR = 1.32; 95%CI: 1.05–1.66). In both two group, restricted cubic splines indicated a J-shaped correlation between SHR and all-cause mortality. In subgroup analysis, SHR was significantly associated with higher 1-year and long-term all-cause mortality among patients without diabetes in both MIMIC-IV and CIN-II cohort. Conclusion Among critical AMI patients, elevated SHR is significantly associated with and 1-year and long-term all-cause mortality, especially in those without diabetes, and the results are consistently in both American and Chinese cohorts.

Two innovative acceleration-layer configuration amendment (CA) schemes are proposed to achieve the CA of constrained redundant robot arms. Specifically, by applying the Zhang neurodynamics equivalency (ZNE) method, an acceleration-layer CA performance indicator is derived theoretically. To obtain a unified-layer inequality constraint by transforming from angle-layer and velocity-layer constraints to acceleration-layer constraints, five theorems and three corollaries are theoretically derived and rigorously proved. Then, together with the unified acceleration-layer bound constraint, an enhanced acceleration-layer CA scheme specially considering three-layer time-variant physical limits is proposed, and a simplified acceleration-layer CA scheme considering three-layer time-invariant physical limits is also proposed. The proposed CA schemes are finally formulated in the form of standard quadratic programming and are solved by a projection neurodynamics solver. Moreover, comparative simulative experiments based on a four-link planar arm and a UR3 spatial arm are performed to verify the efficacy and superiority of the proposed CA schemes. At last, physical experiments are conducted on a real Kinova Jaco2 arm to substantiate the practicability of the proposed CA schemes.

Pulmonary infection is highly prevalent in patients with acute myocardial infarction undergoing percutaneous coronary intervention. However, the potential mechanism is not well characterized. Myocardial ischemia-reperfusion injury (MIRI) induces acute lung injury (ALI) related to pulmonary infection and inflammation. Recent studies have shown that pyroptosis mediates ALI in several human respiratory diseases. It is not known whether MIRI induces pyroptosis in the lungs. Furthermore, ticagrelor is a clinically approved anti-platelet drug that reduces ALI and inhibits the expression levels of several pyroptosis-associated proteins, but the effects of ticagrelor on MIRI-induced ALI have not been reported. Therefore, we investigated whether ticagrelor alleviated ALI in the rat MIRI model, and its effects on pyroptosis in the lungs. Sprague-Dawley rats were randomly divided into four groups: control, MIRI, MIRI plus low ticagrelor (30 mg/kg), and MIRI plus high ticagrelor (100 mg/kg). Hematoxylin and Eosin (HE) staining was performed on the lung sections, and the HE scores were calculated to determine the extent of lung pathology. The wet-to-dry ratio of the lung tissues were also determined. The expression levels of pyroptosis-related proteins such as NLRP3, ASC, and Cleaved caspase-1 were estimated in the lung tissues using the western blot. ELISA was used to estimate the IL-1β levels in the lungs. Immunohistochemistry was performed to determine the levels of MPO-positive neutrophils as well as the total NLRP3-positive and Cleaved caspase-1-positive areas in the lung tissues. The lung tissues from the MIRI group rats showed significantly higher HE score, wet-to-dry ratio, and the MPO-positive area compared to the control group, but these effects were attenuated by pre-treatment with ticagrelor. Furthermore, lung tissues of the MIRI group rats showed significantly higher expression levels of pyroptosis-associated proteins, including NLRP3 (2.1-fold, P < 0.05), ASC (3.0-fold, P < 0.01), and Cleaved caspase-1 (9.0-fold, P < 0.01). Pre-treatment with the high-dose of ticagrelor suppressed MIRI-induced upregulation of NLRP3 (0.46-fold, P < 0.05), ASC (0.64-fold, P < 0.01), and Cleaved caspase-1 (0.80-fold, P < 0.01). Immunohistochemistry results also confirmed that pre-treatment with ticagrelor suppressed MIRI-induced upregulation of pyroptosis in the lungs. In summary, our data demonstrated that MIRI induced ALI and upregulated pyroptosis in the rat lung tissues. Pre-treatment with ticagrelor attenuated these effects.

Abstract Background Coronary catheterization (CC) procedure inevitably exposes patients with cardiovascular disease (CVD) to radiation, while cumulative radiation exposure may lead to higher risk of cancer. Methods This multi-center, retrospective study was based on the CC procedure in Cardiorenal ImprovemeNt II cohort (CIN-II, NCT05050877) among five regional central tertiary teaching hospitals in China between 2007 and 2020. Patients without known cancer were stratified according to the times they received CC procedure. Baseline information from their last CC procedure was analyzed. Cox regression and Fine-Gray competing risk models were used to assess the relationship between cumulative radiation exposure from CC procedures and cancer-specific, all-cause and cardiovascular mortality. Results Of 136,495 hospitalized survivors without cancer at baseline (mean age: 62.3 ± 11.1 years, 30.9% female), 116,992 patients (85.7%) underwent CC procedure once, 15,184 patients (11.1%) on twice, and 4,319 patients (3.2%) underwent CC procedure more than three times. During the median follow-up of 4.7 years (IQR: 2.5 to 7.4), totally 18,656 patients (13.7%) died after discharge, of which 617 (0.5%) died of lung cancer. Compared with the patients who underwent CC procedure once, the risk of lung cancer mortality increased significantly with the increase of the number of CC procedure (CC 2 times vs. 1 time: HR 1.42, 95% CI 1.13 to 1.78, P

Abstract The El Niño-Southern Oscillation (ENSO) used to affect the Asian summer monsoon (ASM) and Australian summer monsoon (AusSM) precipitation in different ways but global warming may have changed it. This study built robust annual ASM (AusSM) precipitation reconstructions during 1588–2013 (1588–1999) to examine the ENSO-monsoon relationship and how it has changed. During the period of 1588–1850 when natural climate variability was dominant, the ENSO-monsoon and inter-monsoon relationship was weak and non-stationary. Since 1850, however, both the inter-monsoon and ENSO-monsoon relationships saw an enhancement and this trend has been persistent to the present day, suggesting the influence of anthropogenic climate warming. Further analysis of climate model projections found that global warming can strengthen the ENSO-monsoon association that, subsequently, acts to synchronize the ASM and AusSM variations.

Background: It is unclear whether serum calcium on admission is associated with clinical outcomes in dilated cardiomyopathy (DCM). In this study, we conducted a retrospective study spanning a decade to investigate the prognostic value of baseline calcium in elderly patients with DCM. Methods: A total of 1,089 consecutive elderly patients (age ≥60 years) diagnosed with DCM were retrospectively enrolled from January 2010 to December 2019. Univariate and multivariate analyses were performed to investigate the association of serum calcium with their clinical outcomes. Results: In this study, the average age of the subjects was 68.36 ± 6.31 years. Receiver operating characteristic (ROC) curve analysis showed that serum calcium level had a great sensitivity and specificity for predicting in-hospital death, with an AUC of 0.732. Kaplan–Meier survival analysis showed that patients with a serum calcium >8.62 mg/dL had a better prognosis than those with a serum calcium ≤8.62 mg/dL (log-rank χ2 40.84, p < 0.001). After adjusting for several common risk factors, a serum calcium ≤8.62 mg/dL was related to a higher risk of long-term mortality (HR: 1.449; 95% CI: 1.115~1.882; p = 0.005). Conclusions: Serum calcium level could be served as a simple and affordable tool to evaluate patients’ prognosis in DCM.

IntroductionIt is unclear whether admission-blood-glucose-to-albumin ratio (AAR) predicts adverse clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) who are treated with percutaneous coronary intervention (PCI). Here, we performed a observational study to explore the predictive value of AAR on clinical outcomes.MethodsPatients diagnosed with STEMI who underwent PCI between January 2010 and February 2020 were enrolled in the study. The patients were classified into three groups according to AAR tertile. The primary outcome was in-hospital all-cause mortality, and the secondary outcomes were in-hospital major adverse cardiac events (MACEs), as well as all-cause mortality and MACEs during follow-up. Logistic regression, Kaplan–Meier analysis, and Cox proportional hazard regression were the primary analyses used to estimate outcomes.ResultsAmong the 3,224 enrolled patients, there were 130 cases of in-hospital all-cause mortality (3.9%) and 181 patients (5.4%) experienced MACEs. After adjustment for covariates, multivariate analysis demonstrated that an increase in AAR was associated with an increased risk of in-hospital all-cause mortality [adjusted odds ratio (OR): 2.72, 95% CI: 1.47–5.03, P = 0.001] and MACEs (adjusted OR: 1.91, 95% CI: 1.18–3.10, P = 0.009), as well as long-term all-cause mortality [adjusted hazard ratio (HR): 1.64, 95% CI: 1.19–2.28, P = 0.003] and MACEs (adjusted HR: 1.58, 95% CI: 1.16–2.14, P = 0.003). Receiver operating characteristic (ROC) curve analysis indicated that AAR was an accurate predictor of in-hospital all-cause mortality (AUC = 0.718, 95% CI: 0.675–0.761) and MACEs (AUC = 0.672, 95% CI: 0.631–0.712).DiscussionAAR is a novel and convenient independent predictor of all-cause mortality and MACEs, both in-hospital and long-term, for STEMI patients receiving PCI.

Abstract Background The triglyceride glucose (TyG) index is an alternative to insulin resistance (IR) as an early indicator of worsening heart failure (HF). Patients with secondary mitral regurgitation (sMR) often experience progressive deterioration of cardiac function. This study aimed to investigate the relationship between the TyG index and worsening of HF in significant sMR (grade ≥ 2) following percutaneous coronary intervention (PCI). Methods This study enrolled participants with significant sMR following PCI from a multicenter cohort study. The patients were divided into the following 3 groups according to tertiles of TyG index: T1, TyG ≤ 8.51; T2, TyG > 8.51 to ≤ 8.98; and T3, TyG > 8.98. The main clinical outcome was worsening HF including unplanned rehospitalization or unscheduled physician office/emergency department visit due to HF and unplanned mitral valve surgery. Results A total of 922 patients (mean ± SD age, 64.1 ± 11.0 years; 79.6% male) were enrolled. The incidence of worsening HF was 15.5% in T1, 15.7% in T2, and 26.4% in T3. In the multivariable model, the highest TyG tertile (T3 group) was more strongly correlated with worsening HF than the lowest tertile (T1 group) after adjusting for confounders (adjusted hazard ratio, 2.44; 95% confidence interval, 1.59–3.72; P

A recent synthesis study found 54% of the high-latitude peatlands have been drying and 32% have been wetting over the past centuries, illustrating their complex ecohydrological dynamics and highly uncertain responses to a warming climate.

Abstract Background The association between prothrombin time-international normalized ratio (PT-INR) and long-term prognosis among patients with coronary artery disease (CAD) without atrial fibrillation or anticoagulant therapy was still unclear. We analyzed the association of PT-INR levels and long-term mortality in a large cohort of CAD patients without atrial fibrillation or using of anticoagulant drugs. Methods We obtained data from 44,662 patients who were diagnosed with CAD and had follow-up information from January 2008 to December 2018. The patients were divided into 4 groups (Quartile 1: PT-INR ≤ 0.96; Quartile2: 0.96 1.06). The main endpoint was long-term all-cause death. Kaplan–Meier curve analysis and Cox proportional hazards models were used to investigate the association between quartiles of PT-INR levels and long-term all-cause mortality. Results During a median follow-up of 5.25 years, 5613 (12.57%) patients died. We observed a non-linear shaped association between PT-INR levels and long-term all-cause mortality. Patients in high PT-INR level (Quartile4: PT-INR > 1.06) showed a significantly higher long-term mortality than other groups (Quartile2 or 3 or 4), (Compared with Quartile 1, Quartile 2 [0.96 1.06], aHR = 1.33, 95% CI 1.22–1.45, P

Abstract Background Mesenchymal stem cells (MSCs) are promising candidates for tissue regeneration and disease treatment. However, long-term in vitro passaging leads to stemness loss of MSCs, resulting in failure of MSC therapy. This study investigated whether the combination of melatonin and human umbilical cord mesenchymal stem cells (hUC-MSCs) was superior to hUC-MSCs alone in ameliorating high-fat diet and streptozocin (STZ)-induced type II diabetes mellitus (T2DM) in a mouse model. Methods Mice were divided into four groups: normal control (NC) group; T2DM group; hUC-MSCs treatment alone (UCMSC) group and pretreatment of hUC-MSCs with melatonin (UCMSC/Mel) group. Results RNA sequence analysis showed that certain pathways, including the signaling pathway involved in the regulation of cell proliferation signaling pathway, were regulated by melatonin. The blood glucose levels of the mice in the UCMSC and UCMSC/Mel treatment groups were significantly reduced compared with the T2DM group without treatment (P

Monocyte-to-M0/M1 macrophage differentiation with unclear molecular mechanisms is a pivotal cellular event in many cardiovascular diseases including atherosclerosis. Long non-coding RNAs (lncRNAs) are a group of protein expression regulators; however, the roles of monocyte-lncRNAs in macrophage differentiation and its related vascular diseases are still unclear. The study aims to investigate whether the novel leukocyte-specific lncRNA Morrbid could regulate macrophage differentiation and atherogenesis. We identified that Morrbid was increased in monocytes and arterial walls from atherosclerotic mouse and from patients with atherosclerosis. In cultured monocytes, Morrbid expression was markedly increased during monocyte to M0 macrophage differentiation with an additional increase during M0 macrophage-to-M1 macrophage differentiation. The differentiation stimuli-induced monocyte–macrophage differentiation and the macrophage activity were inhibited by Morrbid knockdown. Moreover, overexpression of Morrbid alone was sufficient to elicit the monocyte–macrophage differentiation. The role of Morrbid in monocyte–macrophage differentiation was also identified in vivo in atherosclerotic mice and was verified in Morrbid knockout mice. We identified that PI3-kinase/Akt was involved in the up-regulation of Morrbid expression, whereas s100a10 was involved in Morrbid-mediated effect on macrophage differentiation. To provide a proof of concept of Morrbid in pathogenesis of monocyte/macrophage-related vascular disease, we applied an acute atherosclerosis model in mice. The results revealed that overexpression of Morrbid enhanced but monocyte/macrophage-specific Morrbid knockout inhibited the monocytes/macrophages recruitment and atherosclerotic lesion formation in mice. The results suggest that Morrbid is a novel biomarker and a modulator of monocyte–macrophage phenotypes, which is involved in atherogenesis.

In contrast to future projections, paleoclimate records often find wetter subtropics in tandem with elevated CO2. Here, a compilation of proxies and simulations are used to reveal the climate dynamics and feedbacks responsible for generating wet subtropics during the mid-Pliocene.

Background: Patients with secondary mitral regurgitation (sMR) often present with greater mortality and comorbidity, which may be predicted by some risk factors. This study was designed to investigate the prognostic meaning of the echocardiographically detected wall motion score index (WMSI) in coronary artery disease (CAD) patients with moderate or severe baseline sMR who underwent percutaneous coronary intervention (PCI) therapy. Methods: The present study was a multi-center and prospective cohort of consecutive CAD patients with baseline moderate or severe sMR who underwent PCI. All underwent echocardiography at baseline and at follow-up after PCI to assess sMR and WMSI. The primary endpoint was the persistence of moderate or severe sMR after the second echocardiographic measurement. Logistic and Cox proportional hazards models were constructed for the primary (persistent moderate or severe sMR) and secondary (worsening heart failure [HF]; all-cause mortality; cardiovascular-specific mortality; and major adverse cardiovascular events [MACE]) endpoints. Results: Among 920 participants, 483 had WMSI values of ≥1.47, and 437 were less. Of all the participants, 366 (39.8%) continued to have moderate or severe sMR after the second echocardiogram measurement. After full adjustment for confounders, elevated WMSI after PCI was independently associated with the primary endpoint during 3–12 month follow-up. Similarly, elevated WMSI was associated with increased risk of worsening HF, all-cause mortality, cardiovascular-specific mortality, and MACE. Conclusions: Persistent moderate or severe sMR is common (approximately 40%) in PCI patients. Elevated WMSI in CAD patients after PCI is a predictor of persistent moderate or severe sMR and has independent negative prognostic value. Patients with CAD and sMR should be monitored for WMSI to identify those at higher risk of mortality and comorbidity.

Abstract Background High-sensitivity C-reactive protein (hs-CRP) plays an important role in hypoalbuminemia as a representative of inflammation, which is closely associated with poor prognosis among patients with coronary artery disease (CAD). The present study aimed to evaluate the independent and joint effects of high hs-CRP levels and hypoalbuminemia on long-term mortality among CAD patients. Methods A total of 1449 CAD patients were included from a prospective, multicenter, observational cohort study (REICIN, NCT01402232) of patients referred for coronary angiography (CAG). The primary endpoint was long-term all-cause death. Results During a median follow-up of 2.9 (2.0–3.0) years, a total of 107 (7.4%) patients died. The long-term mortality was higher among CAD patients with high hs-CRP levels (> 3 mg/L) than those with the low hs-CRP levels (≤ 3 mg/L; 10.7% versus 4.1%; hazard ratio [HR] 2.49; 95% confidence interval [CI] 1.48–4.17). Similarly, CAD patients with hypoalbuminemia had higher mortality than those without hypoalbuminemia (12.2% versus 4.9%; HR 1.93; 95% CI 1.20–3.08). When hs-CRP and albumin were combined, CAD patients with high hs-CRP levels (> 3 mg/L) and with hypoalbuminemia were at the highest risk of death compared with their reference group (hs-CRP ≤ 3 mg/L and albumin > 35 g/L; HR 3.79; 95% CI 1.91–7.52). Conclusions High hs-CRP levels and hypoalbuminemia were independently and jointly associated with long-term mortality among CAD patients. Patients with high hs-CRP levels and hypoalbuminemia had the highest risk of long-term mortality compared with other groups.

Abstract Background The impact of thrombocytopenia on infection in patients with ST-elevation myocardial infarction (STEMI) remains poorly understood. Aims To evaluate the association between thrombocytopenia and infection in patients with STEMI. Methods Patients diagnosed with STEMI were identified from January 2010 to June 2016. The primary endpoint was in-hospital infection, and major adverse clinical events (MACE) and all-cause death were considered as secondary endpoints. Results A total of 1401 STEMI patients were enrolled and divided into two groups according to the presence (n = 186) or absence (n = 1215) of thrombocytopenia. The prevalence of in-hospital infection was significantly higher in the thrombocytopenic group (30.6% (57/186) vs. 16.2% (197/1215), p

BackgroundPrevious Study Found That Implantation of a Cardioverter-Defibrillator Likely Caused a Worse Prognosis in Older Patients With non-Ischemic Systolic Heart Failure. This Suggests That More Precise Risk Stratification Is Needed in Elderly Patients. We Conducted a Retrospective Study to Evaluate the Association of α-Hydroxybutyrate Dehydrogenase (α-HBDH) With Mortality During Hospitalization in Elderly Patients With non-Ischemic Dilated Cardiomyopathy (NIDCM).Methods1,019 Elderly Patients (age ≥60 Years) Diagnosed With NIDCM Were Retrospectively Enrolled From January 2010 to December 2019. Univariate and Multivariate Analyses Were Showed to Explore the Relationship Between α-HBDH and in- Hospital Death.ResultsPatients in elevated α-HBDH group (>182 U/L) had a longer hospital stays and higher in-hospital mortality. Univariate logistics regression analysis showed that elevated α-HBDH was significantly related to mortality (OR: 7.004, 95% CI: 3.583–13.693, p < 0.001). Receiver operator characteristic (ROC) curve analysis reflected that α-HBDH levels had excellent predictive power for in-hospital death (AUC = 0.810, 95% CI: 0.745–0.876, p < 0.001). After adjustment of age, serum creatine, albumin and LVEF, multivariate regression analysis validated the association of elevated α-HBDH with increased risk of in-hospital death (p < 0.05).ConclusionsElevated α-HBDH level is significantly related to in-hospital mortality in older patients with NIDCM.

ObjectiveThe role of stereotactic body radiation therapy (SBRT) for treating small hepatocellular carcinoma (sHCC) has gained increasing recognition. However, the prognosis and risk factors for recurrence in patients with sHCC remain unclear. This study investigated the risk factors for the recurrence of hepatitis B virus (HBV)-related sHCC after SBRT.MethodsA total of 240 HBV-related sHCC patients treated with SBRT between March 2011 and March 2020 were retrospectively analyzed. The cumulative probability of recurrence was calculated according to the Kaplan–Meier method. Univariate and multivariate analyses were performed with Cox proportional hazard models.ResultsRecurrent hepatocellular carcinoma developed in 134 (55.8%) patients at a median time of 27 months after SBRT. The one- and two-year rates of recurrence were 20.9 and 45.0%, respectively. The median follow-up time was 30 months. The Cox multivariate analysis indicated that age (P = 0.029, HR [1.019, 1.002–1.037]), tumor size (P = 0.012, HR [1.227, 1.045–1.440]), and aspartate aminotransferase-to-platelet ratio index (APRI) (P = 0.005, HR [1.911, 1.221–2.989]) were independent risk factors for recurrence.ConclusionPatients receiving SBRT for HBV-related sHCC may be at greater risk of recurrence if they have a high APRI score combined with advanced age and large tumor size.

Introduction Current international guidelines recommend ECG monitoring after an ischaemic stroke to detect atrial fibrillation (AF) in order to prevent stroke recurrence. However, optimal strategies to detect AF and the downstream management to prevent stroke recurrence remain to be established. The objective of the study was to explore the use of long-term home-based ECG monitoring for AF detection and stroke prevention in patients with a history of stroke.Methods and analysis This prospective, randomised, open-label trial with blinded endpoint adjudication aimed to evaluate the efficacy of long-term home-based ECG monitoring for AF detection and stroke prevention in a 24-month period. Patients aged >18 years with a history of ischaemic stroke will be stratified according to the time from the index ischaemic stroke: 3 years and then randomised in 1:1 to (1) home-based AF screening and (2) control. The home-based AF screening system comprises (1) a handheld single-lead ECG recorder (Comfit Healthcare Devices, Hong Kong SAR, China) and (2) a patient-facing smartphone application specially designed for the study. Patients randomised to the home-based AF group will record a 30 s single-lead ECG using a specially designed handheld ECG device every morning or when symptomatic. All remotely obtained data will be automatically transmitted in real-time through the study smartphone application to a secured cloud hosting and analysed using an artificial intelligence-based diagnostic system. When a diagnosis of AF is made with the system, the patients will be called back for a formal cardiology consultation within 1 week. The primary endpoint is the time to first detection of AF at 24 months of follow-up. Secondary endpoints include recurrent stroke or transient ischaemic attack, initiation of long-term anticoagulation therapy, hospitalisation for heart failure, cardiovascular death and all-cause death.Ethics and dissemination The study protocol has been approved by the institutional review board of The University of Hong Kong, and Hong Kong West Cluster, Hospital Authority, Hong Kong SAR, China. Results will be published in peer-reviewed journals.Trial registration number NCT04523649.

The existing treatment modalities for skin injuries mainly include dressings, negative-pressure wound treatment, autologous skin grafting, and high-pressure wound treatment. All of these therapies have limitations such as high time cost, the inability to remove inactivated tissue in a timely manner, surgical debridement, and oxygen toxicity. Mesenchymal stem cells have a unique self-renewal ability and wide differentiation potential, and they are one of the most promising stem cell types in cell therapy and have great application prospects in the field of regenerative medicine. Collagen exerts structural roles by promoting the molecular structure, shape, and mechanical properties of cells, and adding it to cell cultures can also promote cell proliferation and shorten the cell doubling time. The effects of collagen on MSCs were examined using Giemsa staining, EdU staining, and growth curves. Mice were subjected to allogeneic experiments and autologous experiments to reduce individual differences; all animals were separated into four groups. Neonatal skin sections were detected by HE staining, Masson staining, immunohistochemical staining, and immunofluorescence staining. We found that the MSCs pretreated with collagen accelerated the healing of skin wounds in mice and canines by promoting epidermal layer repair, collagen deposition, hair follicle angiogenesis, and an inflammatory response. Collagen promotes the secretion of the chemokines and growth factors associated with skin healing by MSCs, which positively influences skin healing. This study supports the treatment of skin injuries with MSCs cultured in medium with collagen added.

Abstract Background Contrast-associated acute kidney injury (CA-AKI) is a common complication with poor prognosis after coronary angiography (CAG). With the prevention methods widely being implemented, the temporal trends of incidence and mortality of CA-AKI are still unknown over the last five years. The study aims to determine the incidence and prognosis of CA-AKI in China. Methods This retrospective cohort study was based on the registry at Guangdong Provincial People’s Hospital in China (ClinicalTrials.gov NCT04407936). We analyzed data from hospitalization patients who underwent CAG and with preoperative and postoperative serum creatinine (Scr) values from January 2013 to December 2017. Results 11,943 patients were included in the study, in which the mean age was 63.01 ± 10.79 years and 8,469 (71.1 %) were male. The overall incidence of CA-AKI was 11.2 %. Compared with 2013, the incidence of CA-AKI in 2017 was significantly increased from 9.7 to 13.0 % (adjusted odds ratios [aOR], 1.38; 95 %CI, 1.13–1.68; P-value

Abstract Background Lower low-density lipoprotein cholesterol (LDL-C) is significantly associated with improved prognosis in patients with coronary artery disease (CAD). However, LDL-C reduction does not decrease all-cause mortality among CAD patients when renal function impairs. The association between low baseline LDL-C (

Abstract Background Several studies have shown that N-terminal pro-B-type natriuretic peptide (NT-proBNP) is strongly correlated with the complexity of coronary artery disease and the prognosis of patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS), However, it remains unclear about the prognostic value of NT-proBNP in patients with NSTE-ACS and multivessel coronary artery disease (MCAD) undergoing percutaneous coronary intervention (PCI). Therefore, this study aimed to reveal the relationship between NT-proBNP levels and the prognosis for NSTE-ACS patients with MCAD undergoing successful PCI. Methods This study enrolled 1022 consecutive NSTE-ACS patients with MCAD from January 2010 to December 2014. The information of NT-proBNP levels was available from these patients. The primary outcome was in-hospital all-cause death. In addition, the 3-year follow-up all-cause death was also ascertained. Results A total of 12 (1.2%) deaths were reported during hospitalization. The 4th quartile group of NT-proBNP (> 1287 pg/ml) showed the highest in-hospital all-cause death rate (4.3%) (P 1568 pg/ml is related to the all-cause and in-hospital deaths.

Abstract Background Several studies have found that a low baseline low -density lipoprotein cholesterol (LDL-C) concentration was associated with poor prognosis in patients with acute coronary syndrome (ACS), which is called the “cholesterol paradox”. Low LDL-C concentration may reflect underlying malnutrition, which was strongly associated with increased mortality. The aim of this study was to investigate the cholesterol paradox in patients with CAD and the effects of malnutrition. Method A total of 41,229 CAD patients admitted to Guangdong Provincial People’s Hospital in China were included in this study from January 2007 to December 2018 and divided into two groups (LDL-C

Objectives: To investigate the factors and virological significance of serum hepatitis B virus (HBV) pregenomic RNA (pgRNA) status after long-term antiviral therapy with nucleos(t)ide analogues (NAs) in patients with chronic hepatitis B (CHB). Methods: In total, 51 treatment-naïve patients with CHB were included in the study. Clinical data were collected at baseline, during 5 years and at year 10 of NA treatment. Serum HBV pgRNA status of 51 patients was determined at year 5. Results: At year 5, 45% of the patients remained positive for HBV pgRNA. There were significant differences in baseline hepatitis B e antigen (HBeAg) status, HBV DNA load and hepatitis B surface antigen (HBsAg) levels between patients testing positive and negative for HBV pgRNA at year 5. Serum HBV pgRNA status and serum HBV DNA load were correlated after 5 years of NA treatment (r = 0.347, P = 0.013). Being HBV pgRNA positive at year 5 was an independent risk factor for sustainedly undetectable HBV DNA after 10 years of NA treatment (odds ratio 13.638, 95% confidence interval 1.32–140.81; P = 0.028). Furthermore, HBV pgRNA status at year 5 was associated with HBV DNA re-appearance at year 10 (P = 0.009). Conclusions: HBV pgRNA status at year 5 can reveal HBV covalently closed circular DNA (cccDNA) activity, and HBV pgRNA positivity after long-term antiviral therapy may indicate higher transcriptional activity of HBV cccDNA. Long-term dynamic monitoring of HBV pgRNA should be considered.

BackgroundPolyene phosphatidylcholine (PPC) has been widely used to treat liver diseases in China. However, there is a lack of post-marketing evidence demonstrating its liver-protective efficiency among patients infected with hepatitis B virus (HBV). This study analyzed the multicenter real-world data to compare the effectiveness of PPC with those of magnesium isoglycyrrhizinate (IsoMag) and glutathione (GSH) in patients with liver injury.MethodsThis study comprised the real-world data analysis of a multicenter, retrospective observational cohort. The data were retrieved from the Cooperative Registry of the Hospital Prescription in China between 1 October 2018, and 30 September 2019. A growth curve analysis was performed to compare the effects of different treatments on liver function longitudinally for up to 30 days after treatment commencement. In addition, the dose effect of the PPC treatment was investigated.ResultsThe final cohort included 6,052 patients with approximately 8% infected with HBV (N = 471). There were 1,649, 1,750, and 2,653 patients in the PPC, GSH, and IsoMag groups, respectively, with an average age of 53.9 years. In patients with HBV infection, the PPC treatment was associated with a significant decline in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (slopes: −3.7, 95% CI, −6.0 to −1.5 U/L/day; −2.4, 95% CI, −4.5 to −0.3 U/L/day, respectively). However, there were no significant differences in the effects among the three groups. In patients without HBV infection, the PPC treatment decreased ALT, AST, γ-glutamyl transferase (GGT), and albumin levels (−5.2, 95% CI, −5.8 to −4.5 U/L/day; −3.5, 95% CI, −4.2 to −2.7 U/L/day; −4.9, 95% CI, −6.2 to −3.7 U/L/day, −0.07, 95% CI, −0.09 to −0.04 g/L/day, respectively) and showed a stronger effect on lowering ALT levels than GSH (−2.6, 95% CI, −3.3 to −1.8 U/L/day, p < 0.05), as well as a stronger effect on lowering GGT levels than IsoMag (−1.4, 95% CI, −2.4 to −0.4 U/L/day, p < 0.05). PPC had no impact on prothrombin activity levels in patients with or without HBV infection. High-dose PPC exhibited a stronger effect on lowering ALT and AST levels than low-dose PPC.ConclusionThis was the first real-world multicenter study to demonstrate that PPC efficiently lowers ALT and AST levels in patients with liver diseases regardless of the status of HBV infection. PPC treatment showed a comparable or better effect compared with GSH and IsoMag treatments. High-dose PPC resulted in a stronger effect than low-dose PPC.

BackgroundAssociations between high serum uric acid (SUA) and cardiovascular diseases have been reported. However, few studies have been conducted to explore the relationship between SUA and long-term all-cause mortality in coronary artery disease (CAD) patients. Our study aims to investigate the relationship between SUA and long-term all-cause mortality in patients with CAD.MethodsFrom January 2007 to December 2018, we divided 33,034 patients with CAD admitted in the Guangdong Provincial People's Hospital into five groups (quintile 1: SUA

BackgroundInfections are not common but important in patients with acute myocardial infarction, and are associated with worse outcomes. Infection was proved to be associated with the use of proton pump inhibitor (PPI) in several cohorts. It remains unclear whether PPI usage affects infection in patients with acute myocardial infarction.MethodsWe consecutively enrolled patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) from January 2010 to June 2018. All patients were divided into the PPI group and non-PPI group according to whether the PPI was used. The primary endpoint was the development of infection during hospitalization.ResultsA total of 3027 patients were finally enrolled, with a mean age of 62.2 ± 12.6 years. 310 (10.2%) patients were developed infection during hospitalization. Baseline characteristics were similar between the PPI and non-PPI groups (n = 584 for each group) after propensity score analysis. PPI usage was significantly associated with infection based on the propensity score matching analysis (adjusted OR = 1.62, 95% CI = 1.02-2.57, P = 0.041). Comparing to patients with non-PPI usage, PPI administration was positively associated with higher risk of in-hospital all-cause mortality (adjusted OR = 3.25, 95% CI = 1.06-9.97, P = 0.039) and in-hospital major adverse clinical events (adjusted OR = 3.71, 95% CI = 1.61-8.56, P = 0.002). Subgroup analysis demonstrated that the impact of PPI on infection was not significantly different among patients with or without diabetes and patients with age ≥65 years or age

BackgroundInfection during hospitalization is a serious complication among patients who suffered from acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI); however, there are no suitable and accurate means to assess risk. This study aimed to develop and validate a simple scoring system to predict post-AMI infection in such patients.MethodsAll patients with ST-segment elevation myocardial infarction (STEMI) undergoing PCI consecutively enrolled from January 2010 to May 2016 were served as derivation cohort, and those from June 2016 to May 2018 as validation cohort, respectively. The primary endpoint was post-AMI infection during hospitalization, and all-cause death and major adverse cardiovascular events (MACE) were considered as secondary endpoints. The simplified risk model was established using logistic regression. The area under the receiver operating curve and calibration of predicted and observed infection risk were calculated.ResultsA 24-point risk score was developed, with infection risk ranging from 0.7 to 99.6% for patients with the lowest and highest score. Seven variables including age, Killip classification, insulin use, white blood cell count, serum albumin, diuretic use, and transfemoral approach were included. This model achieved the same high discrimination in the development and validation cohort (C-statistic:0.851) and revealed adequate calibration in both datasets. The incidences of post-AMI infection increased steadily across risk score groups in both development (1.3, 5.1, 26.3, and 69.1%; P < 0.001) and validation (1.8, 5.9, 27.2, and 79.2%; P < 0.001) cohort. Moreover, the risk score demonstrated good performance for infection, in-hospital all-cause death, and MACE among these patients, as well as in patients with the non-ST-elevation acute coronary syndrome.ConclusionThis present risk score established a simple bedside tool to estimate the risk of developing infection and other in-hospital outcomes in patients with STEMI undergoing PCI. Clinicians can use this risk score to evaluate the infection risk and subsequently make evidence-based decisions.

BackgroundDifferent definitions of contrast-associated acute kidney injury (CA-AKI) have different predictive effects on prognosis. However, few studies explored the relationship between these definitions and long-term prognosis in patients with congestive heart failure (CHF). Thus, we aimed to evaluate this association and compared the population attributable risks (PAR) of different CA-AKI definitions.MethodsThis study enrolled 2,207 consecutive patients with CHF undergoing coronary angiography (CAG) in Guangdong Provincial People's Hospital. Two different definitions of CA-AKI were used: CA-AKIA was defined as an increase ≥.5 mg/dl or > 25% in serum creatinine (SCr) from baseline within 72 h after CAG, and CA-AKIB was defined as an increase of ≥.3 mg/dl or > 50% in SCr from baseline within 48 h after CAG. Kaplan-Meier methods and Cox regression were applied to evaluate the association between CA-AKI with long-term mortality. Population attributable risk (PAR) of different definitions for long-term prognosis was also calculated.ResultsDuring the 3.8-year median follow-up (interquartile range 2.1-6), the overall long-term mortality was 24.9%, and the long-term mortality in patients with the definitions of CA-AKIA and CA-AKIB were 30.4% and 34.3%, respectively. We found that CA-AKIA (HR: 1.44, 95% CI 1.19-1.74) and CA-AKIB (HR: 1.48, 95% CI 1.21-1.80) were associated with long-term mortality. The PAR was higher for CA-AKIA (9.6% vs. 8%).ConclusionsOur findings suggested that CA-AKI was associated with long-term mortality in patients with CHF irrespective of its definitions. The CA-AKIA was a much better definition of CA-AKI in patients with CHF due to its higher PAR. For these patients, cardiologists should pay more attention to the presence of CA-AKI, especially CA-AKIA.

BackgroundWhether women have a higher risk of adverse events compared with men following coronary angiography (CAG) and percutaneous coronary intervention (PCI) remains controversial. We aimed to investigate the sex differences in characteristics, treatments and outcomes among patients undergoing CAG and PCI in a large Chinese cohort.MethodsWe analyzed patients undergoing CAG and/or PCI in this multi-center registry cohort study Cardiorenal ImprovemeNt II (CIN-II) in 5 Chinese tertiary hospitals from 2007 to 2020. Clinical characteristics, treatment (discharge medication and PCI) and in-hospital outcomes (mortality and major bleeding) were compared between women and men.ResultsTotally 141,459 patients underwent CAG (44,362 [31.4%] women), of which 69,345 patients underwent PCI (15,376 [22.2%] women). Women were older (64.4 vs. 60.8 years), had more chronic comorbidities and lower PCI rate for stable coronary artery disease (CAD) than men (52.8 vs. 64.2%). Women received less CAG and PCI procedures. Among women undergoing PCI they received similar discharge medication treatment. In addition, women undergoing PCI had mildly lower rate of major bleeding (0.2 vs. 0.3%, P = 0.033) but higher in-hospital mortality (1.2 vs. 0.8%, P < 0.001). After adjustment, women had a higher risk in the major bleeding (adjusted odds ratio, 2.04 [95% CI: 1.07 to 3.62]), and the in-hospital mortality (adjusted odds ratio, 1.87 [95% CI: 1.36 to 2.56]).ConclusionAmong our Chinese cohort, women are older with more chronic comorbidities, receiving less PCI procedure and similar discharge medication treatment. Women have nearly 90% higher risk of in-hospital mortality and over 1-fold increased risk of major bleeding after PCI compared with men.

Serum hepatitis B virus pregenomic RNA (HBV pgRNA) is a potential biomarker that is correlated with covalently closed circular DNA. The long-term dynamics of HBV pgRNA in patients with chronic hepatitis B need to be explored. One hundred naïve nucleos(t)ide analog-treated patients with chronic hepatitis B were enrolled to analyze the dynamics of HBV pgRNA over 9 years. The positive rates of HBV pgRNAs declined gradually and showed biphasic kinetics. Serum HBV pgRNA levels in patients treated with entecavir became negative later than those treated with adefovir or lamivudine. Patients who remain positive for HBV pgRNA after 9 years of treatment may have higher viral transcription efficiencies. The reverse transcription efficiency of hepatitis B e-antigen (HBeAg)-positive patients was higher than that of HBeAg-negative patients at baseline and showed no difference after 24-week nucleos(t)ide analog treatment. The trajectory of serum HBV pgRNA-negative transformation differs in patients with different characteristics. Long-term dynamic monitoring of serum HBV pgRNA levels has significance in hepatitis B treatment.

ObjectivesThe aim of this study was to develop and validate a novel risk score to predict in-hospital mortality in patients with acute myocardial infarction (AMI) using the Heart Failure after Acute Myocardial Infarction with Optimal Treatment (HAMIOT) cohort in China.MethodsThe HAMIOT cohort was a multicenter, prospective, observational cohort of consecutive patients with AMI in China. All participants were enrolled between December 2017 and December 2019. The cohort was randomly assigned (at a proportion of 7:3) to the training and validation cohorts. Logistic regression model was used to develop and validate a predictive model of in-hospital mortality. The performance of discrimination and calibration was evaluated using the Harrell’s c-statistic and the Hosmer-Lemeshow goodness-of-fit test, respectively. The new simplified risk score was validated in an external cohort that included independent patients with AMI between October 2019 and March 2021.ResultsA total of 12,179 patients with AMI participated in the HAMIOT cohort, and 136 patients were excluded. In-hospital mortality was 166 (1.38%). Ten predictors were found to be independently associated with in-hospital mortality: age, sex, history of percutaneous coronary intervention (PCI), history of stroke, presentation with ST-segment elevation, heart rate, systolic blood pressure, initial serum creatinine level, initial N-terminal pro-B-type natriuretic peptide level, and PCI treatment. The c-statistic of the novel simplified HAMIOT risk score was 0.88, with good calibration (Hosmer–Lemeshow test: P = 0.35). Compared with the Global Registry of Acute Coronary Events risk score, the HAMIOT score had better discrimination ability in the training (0.88 vs. 0.81) and validation (0.82 vs. 0.72) cohorts. The total simplified HAMIOT risk score ranged from 0 to 121. The observed mortality in the HAMIOT cohort increased across different risk groups, with 0.35% in the low risk group (score ≤ 50), 3.09% in the intermediate risk group (50 < score ≤ 74), and 14.29% in the high risk group (score > 74).ConclusionThe novel HAMIOT risk score could predict in-hospital mortality and be a valid tool for prospective risk stratification of patients with AMI.Clinical Trial Registration[https://clinicaltrials.gov], Identifier: [NCT03297164].

Background: The identification of asymptomatic structural and functional cardiac abnormalities can help us to recognize early and intervene in patients at pre-heart failure (HF). However, few studies have adequately evaluated the associations of renal function and left ventricular (LV) structure and function in patients at high risk of cardiovascular diseases (CVD). Methods: Patients undergoing coronary angiography and/or percutaneous coronary interventions were enrolled from the Cardiorenal ImprovemeNt II (CIN-II) cohort study, and their echocardiography and renal function were assessed at admission. Patients were divided into five groups according to their estimated glomerular filtration rate (eGFR). Our outcomes were LV hypertrophy and LV systolic and diastolic dysfunction. Multivariable logistic regression analyses were conducted to investigate the associations of eGFR with LV hypertrophy and LV systolic and diastolic dysfunction. Results: A total of 5610 patients (mean age: 61.6 ± 10.6 years; 27.3% female) were included in the final analysis. The prevalence of LV hypertrophy assessed by echocardiography was 29.0%, 34.8%, 51.9%, 66.7%, and 74.3% for the eGFR categories >90, 61–90, 31–60, 16–30, and ≤15 mL/min per 1.73 m2 or for patients needing dialysis, respectively. Multivariate logistic regression analysis showed that subjects with eGFR levels of ≤15 mL/min per 1.73 m2 or needing dialysis (OR: 4.66, 95% CI: 2.96–7.54), as well as those with eGFR levels of 16–30 (OR: 3.87, 95% CI: 2.43–6.24), 31–60 (OR: 2.00, 95% CI: 1.64–2.45), and 61–90 (OR: 1.23, 95% CI: 1.07–1.42), were significantly associated with LV hypertrophy. This reduction in renal function was also significantly associated with LV systolic and diastolic dysfunction (all P for trend

Background: Vascular calcification during aging is highly prevalent in patients with cardiovascular disease; however, there is still no improvement in clarifying the development of vascular calcification. FOSL1 is a transcription regulator belonging to the AP-1 family, which has a unique function in vascular senescence, but its role in vascular calcification needs to be further explored. Methods: Primary mouse vascular smooth muscle cells were isolated and used to construct a calcification model in vitro. Seven-week-old male C57BL/6 mice were used to build the vitD3-induced calcification model in vivo. qRT-PCR and western blot were used to verify the expression of FOSL1 and other genes expressed in vascular smooth muscle cells and aortas. The level of calcification was determined by Alizarin Red S (ARS) staining and the calcium content assay. The level of cellular GSH was detected by the GSH assay kit. Results: Here, we report that FOSL1 was up-regulated after high-calcium/phosphate treatment in both the in vivo and in vitro vascular calcification models. Functional studies have shown that the reduction of FOSL1 attenuates ferroptosis and calcification in vascular smooth muscle cells, as indicated by ARS staining, calcium content assay, and western blot. The inhibition of FOSL1 downregulated the expression of bone-related molecules including Msh Homeobox 2 (MSX2) and tumor necrosis factor receptor superfamily, member 11b/osteoprotegerin (OPG), suggesting that FOSL1 promoted osteogenic differentiation of vascular smooth muscle cells. Furthermore, we found that the ferroptosis-inducing drug erastin can significantly accelerate calcification in the aortic ring while Ferrostatin-1 (fer-1), a drug to protect cells from ferroptosis, can alleviate calcification. Further experiments have shown that inhibiting FOSL1 can promote the expression of ferroptosis-related genes and attenuate calcification. Functionally, cellular GSH levels were increased after the reduction of FOSL1. Conclusions: In this study, we observed a significant protective effect when we reduced the expression of FOSL1 during vascular calcification, and this effect might regulate ferroptosis to a great extent.

Abstract Background Lipid profiles are declined in patients with viral liver cirrhosis and correlated with severity of liver disease. Hepatitis B virus (HBV) is the leading cause of liver cirrhosis in China. Our primary aim was to investigate whether serum lipids and lipoproteins associate with survival in patients with HBV-related cirrhosis and acute gastrointestinal bleeding, and develop a 6-week mortality risk score that incorporates it. Methods From January 2008 to December 2015, consecutive cirrhotic patients with acute gastrointestinal bleeding admitted to our hospital were evaluated and randomly divided into the derivation (n = 629) and validation (n = 314) cohorts. A logistic regression model was established to confirm the association between lipoprotein cholesterol and mortality. Accuracy to predict mortality were assessed by area under the receiver operating characteristic curves (AUROCs) and compared using the Hanley and McNeil test. Results Among study subjects, the 6-week mortality rate was 10.6%. High-density lipoprotein cholesterol (HDL-C) level was found to correlate most strongly with prognostic scores. On ROC analysis, HDL-C showed excellent diagnostic accuracy for 6-week mortality. Logistic regression analysis provided a simple algorithm based on the combined use of 4 variables (total bilirubin (TBIL), HDL-C, International normalized ratio, and hemoglobin), allowing accurate discrimination of 3 distinct prognostic subgroups with 1.7% (low risk), 12.3% (intermediate risk), and 56.9% (high risk) mortality. Its accuracy was significantly better than that of Child–Pugh, model of end-stage liver disease, albumin-bilirubin score, D’Amico model, Augustin model, AIMS65 score and Glasgow-Blatchford score. Baseline HDL-C values ≤ 0.54 mmol/L were associated with markedly lower 6-week survival. Comparable results were found in the validation set. Conclusion HDL-C is a potential indicator for the prognosis of patients with cirrhosis and acute gastrointestinal bleeding. The new algorithm based on HDL-C allowed an accurate predictive assessment of 6-week mortality after bleeding attack.

AimThis study investigated the prevalence and mortality associated with moderate or severe mitral regurgitation (MR) among patients undergoing percutaneous coronary intervention (PCI), with or without heart failure (HF).MethodsWe analyzed patients undergoing PCI without mitral valve surgery from the Cardiorenal ImprovemeNt (CIN) study (ClinicalTrials.gov NCT04407936). Patients without echocardiography to determine MR occurrence or lacking follow-up death data were excluded. Primary endpoints were 1-year and long-term all-cause mortality, with a median follow-up time of 5 years (interquartile range: 3.1–7.6).ResultsOf 28,358 patients undergoing PCI treatment [mean age: 62.7 ± 10.7; women: 6,749 (25.6%)], 3,506 (12.4%) had moderate or severe MR, and there was a higher rate of moderate or severe MR in HF group than non-HF group (28.8 vs. 5.6%, respectively). Regardless of HF conditions, patients with moderate or severe MR were older and had worse cardio-renal function and significantly increased 1-year mortality [adjusted hazard ratio (aHR): 1.82, 95% confidence interval (CI): 1.51–2.2], and long-term mortality [aHR: 1.43, 95% CI: 1.3–1.58]. There was no significant difference between patients with HF and those with non-HF (P for interaction > 0.05).ConclusionOne-eighth of the patients undergoing PCI had moderate or severe MR. Furthermore, one-third and one-seventeenth experienced moderate or severe MR with worse cardiorenal function in the HF and non-HF groups, and increased consistent mortality risk. Further studies should explore the efficacy of mitral interventional procedures for moderate or severe MR after PCI treatment, regardless of HF.

BackgroundLeft ventricular ejection fraction (LVEF) is a vital variable to describe left ventricle systolic function and contractility of left ventricle. However, the association between LVEF and the prognostic effect in patients with moderate or severe mitral regurgitation (MR) is still controversial.MethodsThis study comprised 30,775 coronary artery disease (CAD) patients who underwent coronary arteriography (CAG) in the Cardiorenal ImprovemeNt (CIN) registry from January 2007 to December 2018. Patients were divided into none or mild MR group and moderate or severe MR group, and 3 levels of LVEF ≥50, 40–50%, and

BackgroundPrevious studies have shown that renal function recovery after acute kidney injury (AKI) was associated with decreased risk of all-cause mortality. However, little is known about the correlation between renal function recovery and long-term prognosis in patients with contrast-associated acute kidney injury (CA-AKI) undergoing coronary angiography (CAG).MethodsWe retrospectively enrolled 5,865 patients who underwent CAG. CA-AKI was defined as an increase in serum creatinine (SCr) ≥ 50% or ≥ 0.3 mg/dl from baseline within 72 h post procedure. Recovered CA-AKI was defined as a decrease in SCr to baseline or no CA-AKI level. The first endpoint was long-term all-cause mortality. Kaplan–Meier analysis and Cox regression analysis were used to investigate the association between kidney function recovery and long-term mortality.ResultsDuring the median follow-up period of 5.25 years, the overall long-term mortality was 20.07%, and the long-term mortality in patients with recovered CA-AKI and non-recovered CA-AKI was 17.46 and 27.44%, respectively. After multivariate Cox hazard regression, non-recovered CA-AKI was significantly associated with long-term mortality, while recovered CA-AKI was not [recovered CA-AKI vs. no CA-AKI, hazard ratio (HR) = 1.06, 95% confidence interval (CI): 0.81–1.39, p = 0.661; non-recovered CA-AKI vs. no CA-AKI, HR = 1.39, 95% CI: 1.21–1.60, p < 0.001]. In the subgroup of CAD, both recovered CA-AKI and non-recovered CA-AKI were associated with increased risk of long-term all-cause mortality. However, in other subgroup analyses, only non-recovered CA-AKI was associated with increased risk of long-term all-cause mortality.ConclusionOur results found that non-recovered CA-AKI is significantly associated with long-term mortality. In patients with CAD, recovered CA-AKI can still increase the risk of all-cause mortality. Clinicians need to pay more attention to patients suffering from CA-AKI, whose kidney function has not recovered. In addition, active prevention treatments should be taken by patients with CAD.

ObjectiveSodium glucose cotransporter type 2 inhibitors (SGLT-2i) are beneficial for cardiorenal outcomes in patients with type 2 diabetes mellitus (T2DM), heart failure (HF) or chronic kidney disease (CKD). However, whether or not the patients with coronary artery disease (CAD) have prognostic benefit from SGLT-2i treatment has not been fully studied. The purpose of this meta−analysis is to determine the prognostic benefit of SGLT-2i administration in CAD patients.MethodsWe searched the PubMed, Embase and Cochrane Library from inception until October 15, 2021. We included randomized controlled trials (RCTs) reporting the effect of SGLT-2i on major adverse cardiovascular event (MACE), hospitalization for heart failure (HHF), cardiovascular (CV) death and cardiorenal parameters in CAD patients. Hazard ratio (HR) with 95% confidence interval (CI) and mean difference (MD) from trials were meta-analyzed using fixed-effects models.ResultsNine trials enrolling 15,301 patients with CAD were included in the analyses. Overall, SGLT2i were associated with a reduced risk of MACE (HR: 0.84; 95% CI 0.74–0.95; I2 = 0%), HHF (HR: 0.69; 95% CI 0.58–0.83; I2 = 0%) and a composite of CV death or HHF (HR: 0.78; 95% CI 0.71–0.86; I2 = 37%) in CAD patients. Compared with control group, estimated glomerular filtration rate (eGFR) level decreased less in SGLT-2i group (mean difference [MD] = −3.60, 95% CI, −5.90 to −1.30, p = 0.002; I2 = 0%).ConclusionsSGLT-2i can improve cardiorenal outcomes in CAD patients. Further RCTs and real world studies are need to investigate the effect of SGLT2i on CAD patients.Systematic Review RegistrationPROSPERO, CRD42021258237.

Background: The prognostic value of elevated lipoprotein(a) [Lp(a)] in coronary artery disease (CAD) patients is inconsistent in previous studies, and whether such value changes at different low-density-lipoprotein cholesterol (LDL-C) levels is unclear.Methods and Findings: CAD patients treated with statin therapy from January 2007 to December 2018 in the Guangdong Provincial People's Hospital (NCT04407936) were consecutively enrolled. Individuals were categorized according to the baseline LDL-C at cut-off of 70 and 100 mg/dL. The primary outcome was 5-year all-cause death. Multivariate Cox proportional models and penalized spline analyses were used to evaluate the association between Lp(a) and all-cause mortality. Among 30,908 patients, the mean age was 63.1 ± 10.7 years, and 76.7% were men. A total of 2,383 (7.7%) patients died at 5-year follow-up. Compared with Lp(a)