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ABSTRACT Aims/Introduction Materials and Methods Results Conclusions Diabetes mellitus is a traditional risk factor for heart failure (HF), and glycated albumin (GA) is a marker to assess short‐term glycemic control. Whether GA has prognostic significance in patients with HF remains unclear.A total of 717 patients with HF were enrolled in the prospective cohort study. Patients were grouped by the normal upper limit of GA (17%). Kaplan–Meier analysis and Cox proportional hazards regression were used to evaluate the association between GA and prognosis.During a mean follow‐up of 387 days, 232 composite endpoint events of hospitalization for HF or all‐cause death occurred. Kaplan–Meier analysis showed a higher rate of adverse events in the higher GA group (GA >17%; log‐rank test P < 0.001). GA was an independent predictor of adverse events, both as a continuous variable (per 1% change: hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.00–1.06, P = 0.030) and as a categorical variable (GA >17%: HR 1.36, 95% CI 1.03–1.80, P = 0.032). Restricted cubic splines showed a linear association between GA and adverse events (P for non‐linearity = 0.231). There was no significant difference in adverse outcome risk between those with diabetes and GA ≤17% and those without diabetes, whereas the prognosis was worse in those with diabetes and GA >17% (HR 1.56, 95% CI 1.16–2.11, P = 0.004). Compared to the group with normal levels of GA and glycated hemoglobin, the group with GA >17% and glycated hemoglobin >6.5% had a higher risk of adverse events (HR 1.49, 95% CI 1.06–2.10, P = 0.022).GA was an independent predictor of HF prognosis. Combining GA and glycated hemoglobin might improve the predictive power of adverse outcomes in patients with HF. [ABSTRACT FROM AUTHOR]

The objective of this study is to construct a refined microscopic transport model that elucidates the transport mechanisms of gas flow within micro-nano pores and fractures. The collective impact of various microscopic transport mechanisms was explained through the apparent permeability model, specifically related to gases such as methane and carbon dioxide, within the shale matrix. The apparent permeability models, taking into account microscopic transport mechanisms such as slippage flow, Knudsen diffusion, transition flow, and surface diffusion, were established individually. Subsequently, the influencing factors on apparent permeability were analyzed. The results demonstrate that the apparent permeability of the shale reservoir matrix is significantly influenced by pore pressure, temperature, pore size, and total organic carbon (TOC). As pressure decreases, the apparent permeability of Knudsen diffusion and surface diffusion increases, while the apparent permeability of slippage flow decreases. In addition, the apparent permeability of the reservoir matrix initially decreases and then increases. With increasing temperature, the apparent permeability of slippage flow, Knudsen diffusion, and surface diffusion all increase, as does the apparent permeability of the reservoir matrix. As pore size increases, the apparent permeability of surface diffusion and Knudsen diffusion decreases, while the apparent permeability of slippage flow and the reservoir matrix increases. Furthermore, an increase in TOC leads to no change in the apparent permeability of slippage flow and Knudsen diffusion, but an increase in the apparent permeability of surface diffusion and the reservoir matrix. The model presented in this paper enhances the multi-scale characterization of gas microflow mechanisms in shale and establishes the macroscopic application of these micro-mechanisms. Moreover, this study provides a theoretical foundation for the implementation of carbon capture, utilization, and storage (CCUS) in shale gas production. [ABSTRACT FROM AUTHOR]

Log-structured-merge tree or LSM-tree is a technological underpinning in key-value (KV) stores to support a wide range of performance-critical applications. By conducting data re-organization in the background by virtue of compaction operations, the KV stores have the potential to swiftly service write requests with sequential batched disk writes and read requests for KV items constantly sorted by the compaction. Compaction demands high I/O bandwidth and CPU speed to facilitate quality service to user read/write requests. With the emergence of high-speed SSDs, CPUs are increasingly becoming a performance bottleneck. To mitigate the bottleneck limiting the KV-store's performance and that of the applications supported by the store, we propose a system - gLSM - to leverage GPGPU to remarkably accelerate the compaction operations. gLSM fully utilizes the parallelism and computational capability inside GPGPUs to improve the compaction performance. We design a driver framework to parallelize compaction operations handled between a pair of CPU and GPGPU. We employ data independence and GPGPU-orient radix-sorting algorithm to concurrently conduct compaction. A key-value separation method is devised to slash the transfer of data volume from CPU-side memory to the GPGPU counterpart. The results reveal that gLSM improves the throughput and compaction bandwidth by up to a factor of 2.9 and 26.0, respectively, compared with the four state-of-the-art KV stores. gLSM also reduces the write latency by 73.3%. gLSM exhibits a performance improvement by up to 45% compared against its variant where there are no KV separation and collaboration sort modules. [ABSTRACT FROM AUTHOR]

Background and Aims: Malnutrition is associated with poor prognosis in a wide range of illnesses. However, its long-term prognostic impact in general coronary artery disease (CAD) patients is not well known. We aim to report the prevalence and long-term mortality of malnutrition in the whole general population.Methods and Results: In this retrospective cohort study, the controlling nutritional status (CONUT) score was applied to 46,485 consecutive patients undergoing coronary angiography (CAG) and diagnosed with CAD from January 2007 to July 2018. Patients were stratified as having no malnutrition (n = 19,780), mild (n = 21,092), moderate (n = 5286) and severe malnutrition (n = 327), based on CONUT score. Overall, mean age was 63.1 ± 10.7 years, and 75.8% of patients (n = 35,250) were male. 45.4% of patients were mildly malnourished and 12.1% were moderately or severely malnourished. During a median follow-up of 5.1 years (interquartile range: 3.0-7.7 years), 6093 (17.3%) patients died. After adjusting for confounders, malnutrition risk was associated with significantly increased risk for all-cause death (mild vs. normal, HR = 1.19,95% confidence interval [CI]: 1.12 to 1.28; moderate vs. normal, HR = 1.42,95% CI: 1.30 to 1.55; severe vs. Normal, HR = 1.95, 95% CI: 1.57 to 2.41) (p for trend<0.001). The similar result on all-cause mortality was also found in different subgroups stratified by gender, chronic kidney disease, anemia, percutaneous coronary intervention.Conclusions: Malnutrition is a common complication among patients with CAD, and is strongly associated with increased mortality. Further studies need to explore the efficacy of nutritional interventions on long-term prognosis among CAD patients. This study was registered at Clinicaltrials.gov as NCT04407936. [ABSTRACT FROM AUTHOR]

Background: Inflammation and immune responses play an important role in the pathophysiology of contrast-associated acute kidney injury (CA-AKI), and systemic immune inflammation index (SII) has recently emerged as a new parameter for immune and inflammatory response evaluation. However, limited research has been undertaken to explore the relationship between SII and CA-AKI following coronary angiography (CAG). Patients and Methods: From January 2007 to December 2020, 46,333 patients undergoing CAG were included from 5 Chinese tertiary hospitals. SII was calculated as total peripheral platelets count × neutrophil-to-lymphocyte ratio. Patients were categorized by preprocedural SII quartiles: Q1 ≤ 404.5, Q2 > 404.5 and ≤ 631.7, Q3 > 631.7 and ≤ 1082.8, Q4 > 1082.8. Univariable and multivariable logistic regression were used to reveal the link between preprocedural SII and CA-AKI. Results: A total of the 46,333 patients (62.9 ± 11.5 years, female 28.1%) were included in the study. The incidence of CA-AKI was 8.4% in Q1 group, 8.7% in Q2 group, 9.4% in Q3 group, 15.1% in Q4 group. In the multivariable model, comparing the highest (Q4 group) to lowest (Q1 group) SII level categories, preprocedural SII was related to a higher risk of CA-AKI after fully adjusting for well-known confounders, and there was no statistically difference in the other two SII level categories (Q2 and Q3 groups) compared with Q1 group (adjusted model 3: Q2 group: OR: 0.98, 95% CI: 0.87– 1.11, P = 0.771; Q3 group: OR: 1.04, 95% CI: 0.92– 1.18, P = 0.553; Q4: OR: 1.65, 95% CI: 1.45– 1.88, p < 0.001; P for trend < 0.001). Similar results were found for all the subgroups analysis except for patients undergoing PCI, and the interaction analyses for age, PCI and AMI were significant. In addition, Kaplan–Meier curves demonstrated that the lowest quartile group showed the worst all-cause mortality in a significant SII level-dependent manner among the four groups (Log rank test; p < 0.0001). Conclusion: Elevated preprocedural SII level was a significant and independent risk factor for CA-AKI following CAG. Higher-quality prospective studies are needed to validate the predictive value of SII for CA-AKI. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have shown that the relationship between hypertension (HT) and contrast-associated acute kidney injury (CA-AKI) is not clear. We apply a systematic review and meta-analysis to assess the association between HT and CA-AKI. Methods: We searched for articles on the study of risk factors for CA-AKI in the Embase, Medline, and Cochrane Database of Systematic Reviews (by March 25, 2021). Two authors independently performed quality assessment and extracted data such as the studies' clinical setting, the definition of CA-AKI, and the number of patients. The CA-AKI was defined as a serum creatinine (SCr) increase ≥25% or ≥0.5 mg/dL from baseline within 72 h. We used fixed or random models to pool adjusted OR (aOR) by STATA. Results: A total of 45 studies (2,830,338 patients) were identified, and the average incidence of CA-AKI was 6.48%. There was an increased risk of CA-AKI associated with HT (aOR: 1.378, 95% CI: 1.211–1.567, I2 = 67.9%). In CA-AKI with a SCr increase ≥50% or ≥0.3 mg/dL from baseline within 72 h, an increased risk of CA-AKI was associated with HT (aOR: 1.414, 95% CI: 1.152–1.736, I2 = 0%). In CA-AKI with a Scr increase ≥50% or ≥0.3 mg/dL from baseline within 7 days, HT increases the risk of CA-AKI (aOR: 1.317, 95% CI: 1.049–1.654, I2 = 51.5%). Conclusion: Our meta-analysis confirmed that HT is an independent risk factor for CA-AKI and can be used to identify risk stratification. Physicians should pay more attention toward prevention and treatment of patients with HT in clinical practice. [ABSTRACT FROM AUTHOR]

Background. Previous studies have shown that heart failure (HF) and chronic kidney disease (CKD) have common genetic mechanisms, overlapping pathophysiological pathways, and therapeutic drug—sodium-glucose cotransporter 2 (SGLT2) inhibitors. Methods. The genetic pleiotropy metaCCA method was applied on summary statistics data from two independent meta-analyses of GWAS comprising more than 1 million people to identify shared variants and pleiotropic effects between HF and CKD. Targets of SGLT2 inhibitors were predicted by SwissTargetPrediction and DrugBank databases. To refine all genes, we performed using versatile gene-based association study 2 (VEGAS2) and transcriptome-wide association studies (TWAS) for HF and CKD, respectively. Gene enrichment and KEGG pathway analyses were used to explore the potential functional significance of the identified genes and targets. Results. After metaCCA analysis, 4,624 SNPs and 1,745 genes were identified to be potentially pleiotropic in the univariate and multivariate SNP-multivariate phenotype analyses, respectively. 21 common genes were detected in both metaCCA and SGLT2 inhibitors' target prediction. In addition, 169 putative pleiotropic genes were identified, which met the significance threshold both in metaCCA analysis and in the VEGAS2 or TWAS analysis for at least one disease. Conclusion. We identified novel variants associated with HF and CKD using effectively incorporating information from different GWAS datasets. Our analysis may provide new insights into HF and CKD therapeutic approaches based on the pleiotropic genes, common targets, and mechanisms by integrating the metaCCA method, TWAS and VEGAS2 analyses, and target prediction of SGLT2 inhibitors. [ABSTRACT FROM AUTHOR]

Contrast-associated acute kidney injury (CA-AKI) is a major adverse complication of intravascular administration of contrast medium. Current studies have shown that hypoalbuminemia might be a novel risk factor of CA-AKI. This systematic review and meta-analysis was performed to evaluate the predictive value of hypoalbuminemia for CA-AKI. Relevant studies were identified in Ovid-Medline, PubMed, Embase, and Cochrane Library up to December 31, 2019. Two authors independently screened studies, consulting with a third author when necessary to resolve discrepancies. The pooled odds ratio (OR) was calculated to assess the association between hypoalbuminemia and CA-AKI using a random-effects model or fixed-effects model. Eight relevant studies involving a total of 18 687 patients met our inclusion criteria. The presence of hypoalbuminemia was associated with an increased risk of CA-AKI development (pooled OR: 2.59, 95% CI: 1.80-3.73). Hypoalbuminemia is independently associated with the occurrence of CA-AKI and may be a potentially modifiable factor for clinical intervention. This systematic review and meta-analysis was registered in PROSPERO (CRD42020168104). [ABSTRACT FROM AUTHOR]

Background. Patients with congestive heart failure (CHF) are vulnerable to contrast-induced kidney injury (CI-AKI), but few prediction models are currently available. Therefore, we aimed to establish a simple nomogram for CI-AKI risk assessment for patients with CHF undergoing coronary angiography. Methods. A total of 1876 consecutive patients with CHF (defined as New York Heart Association functional class II-IV or Killip class II-IV) were enrolled and randomly (2:1) assigned to a development cohort and a validation cohort. The endpoint was CI-AKI defined as serum creatinine elevation of ≥0.3 mg/dL or 50% from baseline within the first 48–72 hours following the procedure. Predictors for the simple nomogram were selected by multivariable logistic regression with a stepwise approach. The discriminative power was assessed using the area under the receiver operating characteristic (ROC) curve and was compared with the classic Mehran score in the validation cohort. Calibration was assessed using the Hosmer–Lemeshow test and 1000 bootstrap samples. Results. The incidence of CI-AKI was 9.06% (170) in the total sample, 8.64% (n = 109) in the development cohort, and 9.92% (n = 61) in the validation cohort (P = 0.367). The simple nomogram including four predictors (age, intra-aortic balloon pump, acute myocardial infarction, and chronic kidney disease) demonstrated a similar predictive power as the Mehran score (area under the curve: 0.80 vs. 0.75, P = 0.061), as well as a well-fitted calibration curve. Conclusions. The present simple nomogram including four predictors is a simple and reliable tool to identify CHF patients at risk of CI-AKI, whereas further external validations are needed. [ABSTRACT FROM AUTHOR]

Background: Contrast-associated acute kidney injury (CA-AKI) is a common complication in patients undergoing coronary angiography (CAG). However, few studies demonstrate the association between the prognosis and developed CA-AKI in the different periods after the operation.Methods: We retrospectively enrolled 3206 patients with preoperative serum creatinine (Scr) and at least twice SCr measurement after CAG. CA-AKI was defined as an increase ≥50% or ≥0.3 mg/dL from baseline in the 72 hours after the procedure. Early CA-AKI was defined as having the first increase in SCr within the early phase (<24 hours), and late CA-AKI was defined as an increase in SCr that occurred for the first time in the late phase (24-72 hours). The first endpoint of this study was long-term all-cause mortality. Kaplan-Meier analysis was used to count the cumulative mortality, and the log-rank test was used to assess differences between curves. Univariate and multivariate cox regression analyses were performed to assess whether patients who developed different type CA-AKI were at increased risk of long-term mortality.Results: The number of deaths in the 3 groups was 407 for normal (12.7%), 106 for early CA-AKI (32.7%) and 57 for late CA-AKI (17.7%), during a median follow-up period of 3.95 years. After adjusting for important clinical variables, early CA-AKI (HR = 1.33, 95% CI: 1.02-1.74, P=0.038) was significantly associated with mortality, while late CA-AKI (HR = 0.92, 95% CI: 0.65-1.31, P=0.633) was not. The same results were found in patients with coronary artery disease, chronic kidney disease, diabetes mellitus, and percutaneous coronary intervention.Conclusions: Early increases in Scr, i.e., early CA-AKI, have better predictive value for long-term mortality. Therefore, in clinical practice, physicians should pay more attention to patients with early renal injury related to long-term prognosis and give active treatment. [ABSTRACT FROM AUTHOR]

Background: Acute myocardial infarction (AMI), characterized by an event of myocardial necrosis, is a common cardiac emergency worldwide. However, the genetic mechanisms of AMI remain largely elusive. Methods: A genome-wide association study dataset of AMI was obtained from the CARDIoGRAMplusC4D project. A transcriptome-wide association study (TWAS) was conducted using the FUSION tool with gene expression references of the left ventricle and whole blood. Significant genes detected by TWAS were subjected to Gene Ontology (GO) enrichment analysis. Then the TWAS results of AMI were integrated with mRNA expression profiling to identify common genes and biological processes. Finally, the identified common genes were validated by RT-qPCR analysis. Results: TWAS identified 1,050 genes for the left ventricle and 1,079 genes for whole blood. Upon comparison with the mRNA expression profile, 4 common genes were detected, including HP (PTWAS = 1.22 × 10–3, PGEO = 4.98 × 10–2); CAMP (PTWAS = 2.48 × 10–2, PGEO = 2.36 × 10–5); TNFAIP6 (PTWAS = 1.90 × 10–2, PGEO = 3.46 × 10–2); and ARG1 (PTWAS = 8.35 × 10–3, PGEO = 4.93 × 10–2). Functional enrichment analysis of the genes identified by TWAS detected multiple AMI-associated biological processes, including autophagy of mitochondrion (GO: 0000422) and mitochondrion disassembly (GO: 0061726). Conclusion: This integrative study of TWAS and mRNA expression profiling identified multiple candidate genes and biological processes for AMI. Our results may provide a fundamental clue for understanding the genetic mechanisms of AMI. [ABSTRACT FROM AUTHOR]

Background. Several studies have reported conflicting findings regarding the association between tumor necrosis factor-alpha (TNF-α) genetic polymorphisms and acute kidney injury (AKI). Therefore, we performed this meta-analysis to further investigate whether TNF-α variants are related to AKI susceptibility. Methods. A comprehensive search of observational studies on the association of TNF-α polymorphism with AKI susceptibility was conducted in the PubMed, Cochrane, and Embase databases through February 10, 2020. Pooled odds ratios (ORs) and 95% corresponding confidence intervals (95% CIs) were analyzed to evaluate the strength of the relationship. Results. A total of 8 studies involving 6694 patients (2559 cases and 4135 controls) were included. Pooled analysis showed a trend of increased risk between the TNF-α rs1800629 variant and AKI (A vs. G: OR 95 % CI = 1.33 0.98 ‐ 1.81 ) among the overall population. Ethnicity-stratified analysis indicated that the TNF-α rs1800629 variant was a risk factor for Asians (OR 95 % CI = 1.93 1.59 ‐ 2.35 ) while it is not for Caucasians (OR 95 % CI = 1.04 0.91 ‐ 1.20 ). Additionally, we also found that TNF-α rs1799964 polymorphism was observed to have a significant relationship with AKI risk in Asian patients (C vs. T, OR 95 % CI = 1.26 1.11 ‐ 1.43 ). Conclusions. The TNF rs1800629 polymorphism exhibited a trend toward AKI susceptibility with ethnic differences. The relationship was found to be significant among the Asian population, but not among those of Caucasian origin. Additionally, the TNF-α rs1799964 polymorphism was also related to a significantly increased risk of AKI in Asians. [ABSTRACT FROM AUTHOR]

Introduction: Renin-angiotensin system inhibitors (RASi) reduce mortality among heart failure (HF) patients, but their effect among those complicating contrast-induced acute kidney injury (CI-AKI) remains unexplored. We aimed to investigate whether the relationship between RASi prescription at discharge and mortality differs between HF patients with or without CI-AKI following coronary angiography (CAG).Methods: About 596 HF patients from an observational cohort were divided into a CI-AKI group (n = 104) and a non-CI-AKI group (n = 492) based on whether they had CI-AKI following CAG. The endpoint was all-cause mortality. Multivariable Cox regression was performed in each group to explore the associations between RASi at discharge and mortality.Results: During the median follow-up time of 2.26 (1.70; 3.24) years, higher mortality rate was observed in the CI-AKI group compared to the non-CI-AKI group (18.3% vs 8.9%, p = 0.002). Among HF patients with CI-AKI, after adjusting for confounding factors, the association was not significant between RASi prescription at discharge and mortality (HR: 0.39, 95%CI: 0.12-1.31, p = 0.128), while it was among those without CI-AKI (HR: 0.39, 95%CI: 0.18-0.84, p = 0.016).Conclusion: RASi prescription at discharge for HF patients complicating CI-AKI tended to be ineffective, while it benefited those without CI-AKI. Further randomized evidence is needed to confirm this trend. [ABSTRACT FROM AUTHOR]

There remain few data about the role of homeostatic compaction in hepatic polarization. A previous study has found that mechanical compaction can accelerate hepatocyte polarization; however, the cellular mechanism underlying the effect is mostly unclear. Hepatocyte nuclear factor 4 alpha (HNF4α) is crucial for hepatic polarization in liver morphogenesis. Therefore, we sought to identify any possible involvement of HNF4α in the process of hepatocyte polarization accelerated by mechanical compaction. We first verified in the nonhepatic cell model HEK-293T, and the hepatic cell model primary hepatocytes that the mechanical compaction on cell aggregates simulated by using transient centrifugation can directly activate the expression of HNF4α promoters. Moreover, data using primary hepatocytes showed that the HNF4α expression is positively associated with the levels of compaction force: 2.1-folds higher at the mRNA level and 2.1-folds higher at the protein level for 500 g vs. 0 g. Furthermore, activated HNF4α expression is associated with the enhanced biliary canalicular formation and the increased production of albumin and urea. Pretreatment with Latrunculin B, an inhibitor of F-actin, and SHE78-7, an inhibitor of E-cadherin, which both interrupt the pathway of mechanical transduction, partially but significantly reduced the HNF4α expression and production of albumin and urea. In conclusion, HNF4α can be actively involved in the hepatic polarization in the context of environmental mechanical compaction. [ABSTRACT FROM AUTHOR]

Background: Mitral regurgitation (MR) has a high prevalence and aggravates hypoperfusion and hypoxia in heart failure (HF). Renal tubular epithelial cells are sensitive to hypoxia, and therefore tubulointerstitial damage is quite common in HF. However, the correlation between tubular dysfunction and MR has not been studied. The aim of this work was to evaluate the prognostic significance of urinary N-acetyl- β -d-glucosaminidase (uNAG), a biomarker of renal tubular damage, in patients with HF and MR., Methods: This was a prospective cohort study of 390 patients (mean age 64 years; 65.6% male) with uNAG measurement on admission (expressed as urinary NAG/urinary creatinine) and at least 1 year of follow-up data. The pre-defined primary endpoint was the composite of all-cause mortality or rehospitalization for HF after discharge. Cox regression analysis, restricted cubic splines, and subgroup analysis were used to investigate the prognostic value of uNAG modeled as a categorical (quartiles) or continuous (per SD increase) variable., Results: A total of 153 (39.23%) patients reached the composite endpoint over a median follow-up time of 1.2 years. The uNAG level correlated with the severity of HF and with the incidence of adverse events. In a multivariable Cox regression model, each SD (13.80 U/g ⋅ Cr) of increased uNAG was associated with a 17% higher risk of death or HF rehospitalization (95% confidence interval, 2-33%, p = 0.022), and a 19% higher risk of HF rehospitalization ( p = 0.027). Subgroup analysis revealed the associations between uNAG and poor prognosis were only significant in younger patients ( ≤ 65 years) and in patients without obvious cardiovascular comorbidities., Conclusions: uNAG levels at admission were associated with the risk of adverse outcomes in patients with HF and MR. Additional studies are needed to further investigate the heart-kidney interaction., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 The Author(s). Published by IMR Press.)

In this study, we investigated band alignments at CdS/epitaxial CuIn x Ga 1- x Se 2 (epi-CIGSe) and epi-CIGSe/GaAs heterointerfaces for solar cell applications using ultraviolet, inverse, and X-ray photoemission spectroscopy (UPS, IPES, and XPS) techniques. We clarified the impacts of KF postdeposition treatment (KF-PDT) at the CdS/epi-CIGSe front heterointerfaces. We found that KF-PDT changed the conduction band alignment at the CdS/epi-CIGSe heterointerface from a cliff to flat configuration, attributed to an increase in the electron affinity ( E A ) and ionization potential ( I P ) of the epi-CIGSe surface because of a decrease in Cu and Ga contents. Herein, we discuss the correlation between the impacts of KF-PDT and the solar cell performance. Furthermore, we also investigated the band alignment at the epi-CIGSe/GaAs rear heterointerface. Electron barriers were formed at the epi-CIGSe/GaAs interface, suppressing carrier recombination as the back surface field. Contrarily, a hole accumulation layer is formed by the valence band bending, which is like Ohmic contact.

Background: Iron deficiency is common in cardiovascular diseases (CVD), e.g., heart failure and coronary heart disease. Soluble transferrin receptor (sTfR) is a promising marker representing unmet cellular iron demands. However, whether higher serum sTfR is associated with increased risk of CVDs needs further investigation. Methods: In the present cross-sectional study, we analyzed data of 4,867 adult participants of the National Health and Nutrition Examination Survey (NHANES) 2017-2018. Linear regression models were employed to identify possible correlations between sTfR and other characteristics. The association between sTfR and CVDs was assessed with univariable and multivariable logistics regression models. Results: The prevalence of CVDs was 9.5% among participants, and higher sTfR levels were found in participants with CVDs ( p < 0.001). Linear regression models revealed positive associations between sTfR and age, body mass index, systolic blood pressure, glycated hemoglobulin A1c, and insulin resistance (all p < 0.001). In the multivariable logistics regression model, the adjusted odds ratio of sTfR for CVDs was 2.05 (per 1 log 2 mg/L, 95% confidence interval: 1.03∼4.05, p = 0.046). Further subgroup analysis identified the associations of sTfR and CVDs were only significant in participants ≥60 years old, or with hypertension (all p < 0.05). Conclusion: Our study demonstrated that increased serum sTfR levels were associated with a high prevalence of cardiovascular diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhu, Liu, Zhao, Chen, Meng, Hong, Xiang and Xie.)

Background: Previous 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)., Methods: We 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., Results: During 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., Conclusion: Our 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Lun, Wang, Liu, Liu, Chen, Ying, Li, Chen, Tan, Chen, Liu and Ye.)

Background: A high level of lipoprotein(a) can lead to a high risk of cardiovascular events or mortality. However, the association of moderately elevated lipoprotein(a) levels (≥15 mg/dL) with long-term prognosis among patients with coronary artery disease (CAD) is still uncertain. Hence, we aim to systematically analyzed the relevance of baseline plasma lipoprotein(a) levels to long-term mortality in a large cohort of CAD patients. Methods: We obtained data from 43,647 patients who were diagnosed with CAD and had follow-up information from January 2007 to December 2018. The patients were divided into two groups (<15 and ≥15 mg/dL). The primary endpoint was long-term all-cause death. Kaplan-Meier curve analysis and Cox proportional hazards models were used to investigate the association between moderately elevated baseline lipoprotein(a) levels (≥15 mg/dL) and long-term all-cause mortality. Results: During a median follow-up of 5.04 years, 3,941 (18.1%) patients died. We observed a linear association between lipoprotein(a) levels and long-term all-cause mortality. Compared with lipoprotein(a) concentrations <15 mg/dL, lipoprotein(a) ≥15 mg/dL was associated with a significantly higher risk of all-cause mortality [adjusted hazard ratio (aHR) 1.10, 95%CI: 1.04-1.16, P -values = 0.001). Similar results were found for the subgroup analysis of non-acute myocardial infarction, non-percutaneous coronary intervention, chronic heart failure, diabetes mellitus, or non-chronic kidney diseases. Conclusion: Moderately elevated baseline plasma lipoprotein(a) levels (≥15 mg/dL) are significantly associated with higher all-cause mortality in patients with CAD. Our finding provides a rationale for testing the lipoprotein(a)-reducing hypothesis with lower targets (even <15 mg/dL) in CAD outcome trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Liu, Wang, Chen, Liu, Liang, Huang, Li, Lun, Ying, Chen, Huang, Xu, Yan, Zhu, Tadesse, Tan, Chen and Liu.)

Background: Although glycated hemoglobin (HbA1c) was considered as a prognostic factor in some subgroup of coronary artery disease (CAD), the specific relationship between HbA1c and the long-term all-cause death remains controversial in patients with CAD. Methods: The study enrolled 37,596 CAD patients and measured HbAlc at admission in Guangdong Provincial People's Hospital. The patients were divided into 4 groups according to HbAlc level (Quartile 1: HbA1c ≤ 5.7%; Quartile 2: 5.7% < HbA1c ≤ 6.1%; Quartile 3: 6.1% < HbA1c ≤ 6.7%; Quartile 4: HbA1c > 6.7%). The study endpoint was all-cause death. The restricted cubic splines and cox proportional hazards models were used to investigate the association between baseline HbAlc levels and long-term all-cause mortality. Results: The median follow-up was 4 years. The cox proportional hazards models revealed that HbAlc is an independent risk factor in the long-term all-cause mortality. We also found an approximate U-shape association between HbA1c and the risk of mortality, including increased risk of mortality when HbA1c ≤ 5.7% and HbA1c > 6.7% [Compared with Quartile 2, Quartile 1 (HbA1c ≤ 5.7), aHR = 1.13, 95% CI:1.01-1.26, P < 0.05; Quartile 3 (6.1% < HbA1c ≤ 6.7%), aHR = 1.04, 95% CI:0.93-1.17, P =0.49; Quartile 4 (HbA1c > 6.7%), aHR = 1.32, 95% CI:1.19-1.47, P < 0.05]. Conclusions: Our study indicated a U-shape relationship between HbA1c and long-term all-cause mortality in CAD patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Ye, Ying, Li, Chen, Wang, Lin, Chen, Lun, Huang, Li, Xu, Tan, Chen, Liu and Liu.)

Background: Post-contrast acute kidney injury (PC-AKI) is a severe complication of cardiac catheterization. Emerging evidence indicated that long non-coding RNAs (lncRNAs) could serve as biomarkers for various diseases. However, the lncRNA expression profile and potential biomarkers in PC-AKI remain unclear. This study aimed to investigate novel lncRNA biomarkers for the early detection of PC-AKI. Methods: lncRNA profile in the kidney tissues of PC-AKI rats was evaluated through RNA sequencing. Potential lncRNA biomarkers were identified through human-rat homology analysis, kidney and blood filtering in rats and verified in 112 clinical samples. The expression patterns of the candidate lncRNAs were detected in HK-2 cells and rat models to evaluate their potential for early detection. Results: In total, 357 lncRNAs were found to be differentially expressed in PC-AKI. We identified lnc-HILPDA and lnc-PRND were conservative and remarkably upregulated in both kidneys and blood from rats and the blood of PC-AKI patients; these lncRNAs can precisely distinguish PC-AKI patients (area under the curve (AUC) values of 0.885 and 0.875, respectively). The combination of these two lncRNAs exhibited improved accuracy for predicting PC-AKI, with 100% sensitivity and 83.93% specificity. Time-course experiments showed that the significant difference was first noted in the blood of PC-AKI rats at 12 h for lnc-HILPDA and 24 h for lnc-PRND. Conclusion: Our study revealed that lnc-HILPDA and lnc-PRND may serve as the novel biomarkers for early detection and profoundly affect the clinical stratification and strategy guidance of PC-AKI., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Dialysis-requiring acute kidney injury (AKI-D) is a potentially serious complication associated with high in-hospital mortality among patients with coronary artery disease (CAD) after coronary angiography (CAG). Patients with existing advanced kidney disease (AKD) have an increased risk of developing AKI-D. However, few studies have investigated the prognosis of AKI-D in patients with both CAD and AKD., Methods: In this observational study, 603 CAD patients with AKD (estimated glomerular filtration rate, eGFR <30 mL/min/1.73 m 2 ) were enrolled. AKI-D was defined as acute or worsening renal failure requiring the initiation of renal dialysis. The primary endpoint was 90-day all-cause mortality. Kaplan-Meier and Cox regression analyses were used to assess the association of AKI-D and 90-day all-cause mortality among CAD patients complicated with AKD., Results: Overall, among 603 CAD patients complicated with AKD, 83 patients (13.8%) required AKI-D. Patients underwent AKI-D had a significantly higher rate of 90-day mortality than those who did not (13.3% vs . 6.5%, log rank P=0.028), with an unadjusted hazard ratio (HR) of 1.28 [95% confidence interval (CI): 1.02-1.61, P=0.032]. After adjustment for cardiac and renal impairment, however, AKI-D was no longer associated with 90-day mortality (HR: 1.08, 95% CI: 0.84-1.39, P=0.559). The attenuation analysis showed that after adjustment for cardiac and renal function, the residual effect of 90-day mortality was as low as 30% of the unadjusted effect., Conclusions: The incidence of AKI-D is high among patients with CAD complicated by AKD. The high 90-day mortality rate of patients undergoing AKI-D is mainly attributable to cardio-renal impairment., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-6365). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

There remain few data about the role of homeostatic compaction in hepatic polarization. A previous study has found that mechanical compaction can accelerate hepatocyte polarization; however, the cellular mechanism underlying the effect is mostly unclear. Hepatocyte nuclear factor 4 alpha (HNF4 α ) is crucial for hepatic polarization in liver morphogenesis. Therefore, we sought to identify any possible involvement of HNF4 α in the process of hepatocyte polarization accelerated by mechanical compaction. We first verified in the nonhepatic cell model HEK-293T, and the hepatic cell model primary hepatocytes that the mechanical compaction on cell aggregates simulated by using transient centrifugation can directly activate the expression of HNF4 α promoters. Moreover, data using primary hepatocytes showed that the HNF4 α expression is positively associated with the levels of compaction force: 2.1-folds higher at the mRNA level and 2.1-folds higher at the protein level for 500 g vs. 0 g. Furthermore, activated HNF4 α expression is associated with the enhanced biliary canalicular formation and the increased production of albumin and urea. Pretreatment with Latrunculin B, an inhibitor of F-actin, and SHE78-7, an inhibitor of E-cadherin, which both interrupt the pathway of mechanical transduction, partially but significantly reduced the HNF4 α expression and production of albumin and urea. In conclusion, HNF4 α can be actively involved in the hepatic polarization in the context of environmental mechanical compaction., Competing Interests: All authors declare no competing financial interests., (Copyright © 2020 Jinlian Yang et al.)

Cancer-associated fibroblasts (CAFs) play crucial roles in enhancing cell survival, proliferation, invasion, and metastasis. We previously showed that hepatocellular carcinoma-derived CAFs (H-CAFs) promoted proliferation of hepatocellular carcinoma (HCC) cells. This study aimed to further explore the role of CAFs in HCC epithelial-mesenchymal transition (EMT) and the underlying mechanism. High CAF density was significantly associated with liver cirrhosis, inferior clinicopathologic characteristics, elevated EMT-associated markers, and poorer survival in human HCC. Within HCC cells, EMT was induced after co-culture with H-CAFs. Secretomic analysis showed that IL-6 and HGF were the key EMT-stimulating cytokines secreted by H-CAFs. Proteomic analysis revealed that TG2 was significantly upregulated in HCC cells with EMT phenotypes. Overexpression of TG2 promoted EMT of HCC cells, and knockdown of TG2 remarkably attenuated the H-CAF-induced EMT. Furthermore, during EMT, TG2 expression was enhanced after HCC cells were stimulated by IL-6, but not HGF. Inhibition of the IL-6/STAT3 signaling decreased TG2 expression. The principal TG2 transcription control element and a potential STAT3 binding site were identified using promoter analysis. Hence, H-CAFs facilitates HCC cells EMT mediated by IL-6, which in turn activates IL-6/IL6R/STAT3 axis to promote TG2 expression., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Oral hydration with water may be inexpensive and effective in the prevention of contrast-induced acute kidney injury (CI-AKI), but its efficacy among ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) remains unknown., Methods: This was a prospective, single-center, observational study. We consecutively enrolled 308 STEMI patients undergoing primary PCI. All patients drank unrestricted amounts of fluids freely, whose volume was recorded until 24 hours following primary PCI. Oral hydration volume/weight ratios (OHV/W) were calculated. Adequate oral hydration was defined as a ratio over 12 mL/kg within 24 hours after primary PCI. The primary outcome measure was CI-AKI, defined as a 25% or 0.5 mg/dL increase in serum creatinine from baseline during the first 48-72 hours post-procedure. The association between adequate post-procedural oral hydration and CI-AKI was assessed using multivariable logistic analysis., Results: Post-procedural prophylactic oral hydration was implemented in 90.91% (280/308) of STEMI patients undergoing primary PCI. There were no differences in the sex, age, weight, index blood pressure, LVEF, anemia, diabetes mellitus, contrast volume used during the coronary procedures between groups (P>0.05). The incidence of CI-AKI was much higher in the inadequate oral hydration group (<12 mL/kg) than the adequate group (≥12 mL/kg) (53.57% vs . 21.79%, P=0.0002). Multivariate logistic regression showed adequate oral hydration (≥12 mL/kg) was the independent protective factor associated with CI-AKI (OR =0.349, 95% CI: 0.147-0.828, P=0.0170), after adjusting confounders, including age, female gender, baseline serum creatinine, diabetes mellitus, use of diuretics, congestive heart failure and intravenous hydration volume., Conclusions: Our study determined the association of post-procedural adequate oral hydration on CI-AKI following primary PCI, which was a potential strategy for CI-AKI prevention among patients with STEMI at very high risk., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.