Incidence, risk factors, and outcomes of acute liver injury in hospitalized adults with acute kidney injury: a large multicenter study.

BACKGROUND: Acute kidney injury (AKI) and acute liver injury (ALI) were associated with poor outcomes during hospitalization, respectively. However, the clinical outcome of AKI combined with ALI (AKI-ALI) remains unknown. The current study aimed to describe AKI-ALI's incidences, risk factors, and outcomes. METHODS: The study population included patients aged 18-99 years with enough serum creatinine and liver testing hospitalized at 19 medical centers throughout China between 2000 and 2021. AKI was defined by Kidney Disease Improving Global Outcomes and ALI was defined by the change of liver enzymes based on Asia Pacific Association of Study of Liver consensus guidelines. Cox proportional hazard model was used to identify risk factors for AKI-ALI, and a time-dependent Cox proportional hazard regression model was used to estimate the association between AKI-ALI and in-hospital mortality. RESULTS: Among the 18,461 patients with AKI, 1689 (9.1%) combined with ALI. Male patients or those who have used nonsteroidal anti-inflammatory drugs or vasopressors, and who have heart failure or shock, with higher AST or GGT values, were associated with an increased risk of AKI-ALI. Compared with AKI-nonALI, patients with AKI-ALI were at higher risk of in-hospitalized mortality (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.54, 2.00). In addition, a stronger association between AKI-ALI and in-hospital mortality was found in those with lower AKI grades (p for interaction = 0.037). CONCLUSIONS: ALI was not uncommon among patients with AKI, especially in patients who used vasopressors and had shock. This study highlights the association between AKI-ALI and a significantly increased risk of mortality. It suggests that dynamic monitoring of liver function is essential, particularly in patients with AST and GGT exceeding the normal upper limit, to improve the in-hospital prognosis of AKI patients.

Dipeptidyl peptidase 4 inhibitors vs. metformin for new-onset dementia: a propensity score-matched cohort study.

BACKGROUND: Hypoglycemic pharmacotherapy interventions for alleviating the risk of dementia remains controversial, particularly about dipeptidyl peptidase 4 (DPP4) inhibitors versus metformin. Our objective was to investigate whether the initiation of DPP4 inhibitors, as opposed to metformin, was linked to a reduced risk of dementia. METHODS: We included individuals with type 2 diabetes over 40 years old who were new users of DPP4 inhibitors or metformin in the Chinese Renal Disease Data System (CRDS) database between 2009 and 2020. The study employed Kaplan-Meier and Cox regression for survival analysis and the Fine and Gray model for the competing risk of death. RESULTS: Following a 1:1 propensity score matching, the analysis included 3626 DPP4 inhibitor new users and an equal number of metformin new users. After adjusting for potential confounders, the utilization of DPP4 inhibitors was associated with a decreased risk of all-cause dementia compared to metformin (hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.45-0.89). Subgroup analysis revealed that the utilization of DPP4 inhibitors was associated with a reduced incidence of dementia in individuals who initiated drug therapy at the age of 60 years or older (HR 0.69, 95% CI 0.48-0.98), those without baseline macrovascular complications (HR 0.62, 95% CI 0.41-0.96), and those without baseline microvascular complications (HR 0.67, 95% CI 0.47-0.98). CONCLUSION: In this real-world study, we found that DPP4 inhibitors presented an association with a lower risk of dementia in individuals with type 2 diabetes than metformin, particularly in older people and those without diabetes-related comorbidities.

Single-cell transcriptomics reveals the ameliorative effect of rosmarinic acid on diabetic nephropathy-induced kidney injury by modulating oxidative stress and inflammation.

Diabetic nephropathy (DN) is a severe complication of diabetes, characterized by changes in kidney structure and function. The natural product rosmarinic acid (RA) has demonstrated therapeutic effects, including anti-inflammation and anti-oxidative-stress, in renal damage or dysfunction. In this study, we characterized the heterogeneity of the cellular response in kidneys to DN-induced injury and RA treatment at single cell levels. Our results demonstrated that RA significantly alleviated renal tubular epithelial injury, particularly in the proximal tubular S1 segment and on glomerular epithelial cells known as podocytes, while attenuating the inflammatory response of macrophages, oxidative stress, and cytotoxicity of natural killer cells. These findings provide a comprehensive understanding of the mechanisms by which RA alleviates kidney damage, oxidative stress, and inflammation, offering valuable guidance for the clinical application of RA in the treatment of DN.

Exploring the potential of VGLL3 methylation as a prognostic indicator for intracranial aneurysm with gender-specific considerations.

DNA methylation is widely recognized to play a role in intracranial aneurysm (IA) pathogenesis. We investigated the levels of methylation of vestigial-like 3 (VGLL3) in IA and explored its potential as a prognostic indicator. A total of 48 patients with IA and 48 healthy controls were included in the present study. Methylation levels of CpG sites were assessed using bisulfite pyrosequencing, and levels of VGLL3, TEAD, and YAP in the blood were measured by real-time quantitative polymerase chain reaction testing. VGLL3 methylation was significantly higher in controls than in IA patients (P=0.001), and this phenomenon was more pronounced in females (P<0.001). Compared with the control group, the expression levels of VGLL3 and TEAD in the blood of IA patients were significantly increased, while YAP was significantly decreased. VGLL3 methylation was positively correlated with HDL (P=0.003) and female Lpa concentration (r = 0.426, P=0.03), and was also negatively correlated with age (P=0.003), APOE (P=0.005), and VGLL3 mRNA expression (P<0.001). Methylation and mRNA expression of VGLL3 may serve as indicators of IA risk in females (AUC = 0.810 and 0.809). VGLL3 methylation may participate in the pathogenesis of IA by regulating the expression of the VGLL3/TEAD/YAP pathway, and its gene methylation and expression levels have IA risk prediction value.

Accurate estimation of biological age and its application in disease prediction using a multimodal image Transformer system.

Aging in an individual refers to the temporal change, mostly decline, in the body's ability to meet physiological demands. Biological age (BA) is a biomarker of chronological aging and can be used to stratify populations to predict certain age-related chronic diseases. BA can be predicted from biomedical features such as brain MRI, retinal, or facial images, but the inherent heterogeneity in the aging process limits the usefulness of BA predicted from individual body systems. In this paper, we developed a multimodal Transformer-based architecture with cross-attention which was able to combine facial, tongue, and retinal images to estimate BA. We trained our model using facial, tongue, and retinal images from 11,223 healthy subjects and demonstrated that using a fusion of the three image modalities achieved the most accurate BA predictions. We validated our approach on a test population of 2,840 individuals with six chronic diseases and obtained significant difference between chronological age and BA (AgeDiff) than that of healthy subjects. We showed that AgeDiff has the potential to be utilized as a standalone biomarker or conjunctively alongside other known factors for risk stratification and progression prediction of chronic diseases. Our results therefore highlight the feasibility of using multimodal images to estimate and interrogate the aging process.

Impact of ITO layer on the spatial optical distribution of semipolar (20-21) InGaN/GaN multiple quantum wells with surface morphology.

Textured surface with micro-facets have been widely observed in semipolar and nonpolar III-nitride heterostructures, mainly resulted from the anisotropic growth rate in the growth plane. Polarization and the intensity distribution of surface emissions are both affected by the surface morphology. The indium tin oxide (ITO) layer, serving as the current spreading layer, are usually employed to enhance the current injection efficiency and light extraction efficiency in III-nitride emitters. For semipolar orientation, the introduction of an ITO layer could weaken the anisotropic optical property, especially for the spatial intensity distribution. This paper reports the influence of the ITO layer on the spatial intensity distribution of semipolar (20-21) InGaN/GaN multiple quantum wells. The intensity distribution could be shaped from a rectangular-like pattern to a circular-like pattern with the deposition of an ITO layer. The ITO layer allows more light along the [11-20] direction to emit out at a small angle with respect to the surface normal. By further increasing the ITO thickness, the influence of surface fluctuation of semipolar sample decreases, leading to an improvement in the proportion of the light at small angles and a slight decrease in the overall integrated intensity of whole far field. These results will help pave the way to high-performance semipolar emitters with great potential in general illumination and backlighting.

Incidence, Risk Factors and Outcome of Postoperative Acute Kidney Injury in China.

BACKGROUND AND HYPOTHESIS: Postoperative acute kidney injury (AKI) is a common condition after surgery, however, the available data about nationwide epidemiology of postoperative AKI in China from the large and high-quality studies is limited. This study was aimed to determine the incidence, risk factors, and outcomes of postoperative AKI among patients undergoing surgery in China. METHODS: This was a large, multicenter, retrospective study performed in 16 tertiary medical centers in China. Adult (at least 18 years old) patients who undergoing surgical procedures from January 1, 2013 to December 31, 2019 were included. Postoperative AKI was defined by the Kidney Disease: Improving Global Outcomes creatinine criteria. The associations of AKI and in-hospital outcomes were investigated using logistic regression models adjusted for potential confounders. RESULTS: Among 520 707 patients included in our study, 25 830 (5.0%) patients developed postoperative AKI. The incidence of postoperative AKI varied by surgery type, which was highest in cardiac (34.6%) surgery, followed by urologic (8.7%), and general (4.2%) surgeries. 89.2% postoperative AKI cases were detected in the first 2 postoperative days. However, only 584 (2.3%) patients with postoperative AKI were diagnosed with AKI on discharge. Risk factors for postoperative AKI included advanced age, male sex, lower baseline kidney function, pre-surgery hospital stay ≤ 3 days or > 7 days, hypertension, diabetes mellitus, and use of PPIs or diuretics. The risk of in-hospital death increased with the stage of AKI. In addition, patients with postoperative AKI had longer length of hospital stay (12 vs 19 days), were more likely to require intensive unit care (13.1% vs 45.0%) and renal replacement therapy (0.4% vs 7.7%). CONCLUSIONS: Postoperative AKI was common across surgery type in China, particularly for patients undergoing cardiac surgery. Implementation and evaluation of an alarm system is important for the battle against postoperative AKI.

Post-treatment level of LDL cholesterol and all-cause mortality in patients with atherosclerotic cardiovascular disease: evidence from real-world setting.

AIMS: This study aimed to evaluate the safety of the currently recommended target of LDL cholesterol (LDL-C) control on mortality in patients with atherosclerotic cardiovascular disease (ASCVD). METHODS AND RESULTS: Using deidentified electronic health record data, we conducted a multicentre retrospective cohort study involving individuals with documented ASCVD who had received statin treatment for at least 3 months across China. The primary outcomes assessed encompassed all-cause mortality, CV mortality, and non-CV mortality. Relationships between post-treatment LDL-C concentrations and outcomes were evaluated using restricted cubic spline curves based on Cox proportional hazards regression analyses. Additionally, competitive risk models were employed to explore associations between LDL-C levels and cause-specific mortality. Among 33 968 participants, we identified nearly linear associations of post-treatment LDL-C level with all-cause mortality and CV mortality during a median follow-up of 47 months. Notably, patients who achieved the recommended target of LDL-C (<1.4 mmol/L) were at significantly lower risks of all-cause mortality [hazard ratio (HR), 0.77; 95% confidence interval (CI), 0.69-0.86] and CV mortality (subdistribution HR, 0.68; 95% CI, 0.58-0.79), compared with those with LDL-C ≥ 3.4 mmol/L. This survival benefit was consistent in patients with different intensities of LDL-C reduction and other subgroup analyses. And no correlation was found between post-treatment LDL-C concentration and non-CV mortality. CONCLUSION: Our findings supported the safety of currently recommended target of LDL-C control and the 'lower is better' principle in patients with ASCVD.

Intensive control of LDL cholesterol (LDL-C) has been widely recommended for cardiovascular (CV) protection in patients with atherosclerotic CV disease. Nevertheless, a U-shaped association between LDL-C levels and all-cause mortality has been noted in several general population studies, prompting concerns regarding the safety of intensive lipid control. In this multicentre cohort comprising 33 968 patients at the highest CV risk, we found that patients with lower post-treatment LDL-C level were at lower risk of both all-cause and CV mortality, and this survival benefit was unaffected by intensity of LDL-C reduction, types of lipid-lowering agents, and other clinical characteristics.

Risk of Hospital-Acquired Acute Kidney Injury among Adult Opioid Analgesic Users: A Multicenter Real-World Data Analysis.

Introduction: Comprehensive data on the risk of hospital-acquired (HA) acute kidney injury (AKI) among adult users of opioid analgesics are lacking. This study aimed to systematically compare the risk of HA-AKI among the users of various opioid analgesics. Methods: This multicenter, retrospective real-world study analyzed 255,265 adult hospitalized patients who received at least one prescription of opioid analgesic during the first 30 days of hospitalization. The primary outcome was the time from the first opioid analgesic prescription to HA-AKI occurrence. 12 subtypes of opioid analgesics were analyzed, including 9 for treating moderate-to-severe pain and 3 for mild-to-moderate pain. We examined the association between the exposure to each subtype of opioid analgesic and the risk of HA-AKI using Cox proportional hazards models, using the most commonly used opioid analgesic as the reference group. Results: As compared to dezocine, the most commonly used opioid analgesic for treating moderate-to-severe pain, exposure to morphine, but not the other 7 types of opioid analgesics, was associated with a significantly increased risk of HA-AKI (adjusted hazard ratio: 1.56, 95% confidence interval: 1.40-1.78). The association was consistent in stratified analyses and in a propensity-matched cohort. There were no significant differences in the risk of HA-AKI among the opioid analgesic users with mild-to-moderate pain after adjusting for confounders. Conclusion: The use of morphine was associated with an increased risk of HA-AKI in adult patients with moderate-to-severe pain. Opioid analgesics other than morphine should be chosen preferentially in adult patients with high risk of HA-AKI when treating moderate-to-severe pain.

Epidemiology and outcomes of post-AKI proteinuria.

Background: Acute kidney injury (AKI) has been associated with increased risks of new-onset and worsening proteinuria. However, epidemiologic data for post-AKI proteinuria was still lacking. This study aimed to determine the incidence, risk factors and clinical correlations of post-AKI proteinuria among hospitalized patients. Methods: This study was conducted in a multicenter cohort including patients aged 18-100 years with hospital-acquired AKI (HA-AKI) hospitalized at 19 medical centers throughout China. The primary outcome was the incidence of post-AKI proteinuria. Secondary outcomes included AKI recovery and kidney disease progression. The results of both quantitative and qualitative urinary protein tests were used to define post-AKI proteinuria. Cox proportional hazard model with stepwise regression was used to determine the risk factors for post-AKI proteinuria. Results: Of 6206 HA-AKI patients without proteinuria at baseline, 2102 (33.9%) had new-onset proteinuria, whereas of 5137 HA-AKI with baseline proteinuria, 894 (17.4%) had worsening proteinuria after AKI. Higher AKI stage and preexisting CKD diagnosis were risk factors for new-onset proteinuria and worsening proteinuria, whereas treatment with renin-angiotensin system inhibitors was associated with an 11% lower risk of incident proteinuria. About 60% and 75% of patients with post-AKI new-onset and worsening proteinuria, respectively, recovered within 3 months. Worsening proteinuria was associated with a lower incidence of AKI recovery and a higher risk of kidney disease progression. Conclusions: Post-AKI proteinuria is common and usually transient among hospitalized patients. The risk profiles for new-onset and worsening post-AKI proteinuria differed markedly. Worsening proteinuria after AKI was associated with adverse kidney outcomes, which emphasized the need for close monitoring of proteinuria after AKI.

Biological effects and mechanisms of fisetin in cancer: a promising anti-cancer agent.

Fisetin, a natural flavonoid, possesses numerous biological activities that have been extensively studied in various diseases. When it comes to cancer, fisetin exhibits a range of biological effects, such as suppressing cell growth, triggering programmed cell death, reducing the formation of new blood vessels, protecting against oxidative stress, and inhibiting cell migration. Moreover, fisetin has the ability to enhance the effectiveness of chemotherapy. The anticancer properties of fisetin can be attributed to a diverse array of molecules and signaling pathways, including vascular endothelial growth factor (VEGF), mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), PI3K/Akt/mTOR, and Nrf2/HO-1. Consequently, fisetin holds promise as a therapeutic agent for anticancer treatment. In this review, we place emphasis on the biological functions and various molecular targets of fisetin in anticancer therapy.

Cytotoxicity of 4 Wild Mushrooms in a Case of Yunnan Sudden Unexplained Death.

OBJECTIVES: To explore the cytotoxicity of four wild mushrooms involved in a case of Yunnan sudden unexplained death (YNSUD), to provide the experimental basis for prevention and treatment of YNSUD. METHODS: Four kinds of wild mushrooms that were eaten by family members in this YNSUD incident were collected and identified by expert identification and gene sequencing. Raw extracts from four wild mushrooms were extracted by ultrasonic extraction to intervene HEK293 cells, and the mushrooms with obvious cytotoxicity were screened by Cell Counting Kit-8 (CCK-8). The selected wild mushrooms were prepared into three kinds of extracts, which were raw, boiled, and boiled followed by enzymolysis. HEK293 cells were intervened with these three extracts at different concentrations. The cytotoxicity was detected by CCK-8 combined with lactate dehydrogenase (LDH) Assay Kit, and the morphological changes of HEK293 cells were observed under an inverted phase contrast microscope. RESULTS: Species identification indicated that the four wild mushrooms were Butyriboletus roseoflavus, Boletus edulis, Russula virescens and Amanita manginiana. Cytotoxicity was found only in Amanita manginiana. The raw extracts showed cytotoxicity at the mass concentration of 0.1 mg/mL, while the boiled extracts and the boiled followed by enzymolysis extracts showed obvious cytotoxicity at the mass concentration of 0.4 mg/mL and 0.7 mg/mL, respectively. In addition to the obvious decrease in the number of HEK293 cells, the number of synapses increased and the refraction of HEK293 cells was poor after the intervention of Amanita manginiana extracts. CONCLUSIONS: The extracts of Amanita manginiana involved in this YNSUD case has obvious cytotoxicity, and some of its toxicity can be reduced by boiled and enzymolysis, but cannot be completely detoxicated. Therefore, the consumption of Amanita manginiana is potentially dangerous, and it may be one of the causes of the YNSUD.

Immunosuppression versus Supportive Care on Kidney Outcomes in IgA Nephropathy in the Real-World Setting.

BACKGROUND: The efficacy of immunosuppression in the management of immunoglobulin A (IgA) nephropathy remains highly controversial. The study was conducted to assess the effect of immunosuppression, compared with supportive care, in the real-world setting of IgA nephropathy. METHODS: A cohort of 3946 patients with IgA nephropathy, including 1973 new users of immunosuppressive agents and 1973 propensity score-matched recipients of supportive care, in a nationwide register data from January 2019 to May 2022 in China was analyzed. The primary outcome was a composite of 40% eGFR decrease of the baseline, kidney failure, and all-cause mortality. A Cox proportional hazard model was used to estimate the effects of immunosuppression on the composite outcomes and its components in the propensity score-matched cohort. RESULTS: Among 3946 individuals (mean [SD] age 36 [10] years, mean [SD] eGFR 85 [28] ml/min per 1.73 m 2 , and mean [SD] proteinuria 1.4 [1.7] g/24 hours), 396 primary composite outcome events were observed, of which 156 (8%) were in the immunosuppression group and 240 (12%) in the supportive care group. Compared with supportive care, immunosuppression treatment was associated with 40% lower risk of the primary outcome events (adjusted hazard ratio, 0.60; 95% confidence interval, 0.48 to 0.75). Comparable effect size was observed for glucocorticoid monotherapy and mycophenolate mofetil alone. In the prespecified subgroup analysis, the treatment effects of immunosuppression were consistent across ages, sexes, levels of proteinuria, and values of eGFR at baseline. Serious adverse events were more frequent in the immunosuppression group compared with the supportive care group. CONCLUSIONS: Immunosuppressive therapy, compared with supportive care, was associated with a 40% lower risk of clinically important kidney outcomes in patients with IgA nephropathy.

Predicting in-hospital outcomes of patients with acute kidney injury.

Acute kidney injury (AKI) is prevalent and a leading cause of in-hospital death worldwide. Early prediction of AKI-related clinical events and timely intervention for high-risk patients could improve outcomes. We develop a deep learning model based on a nationwide multicenter cooperative network across China that includes 7,084,339 hospitalized patients, to dynamically predict the risk of in-hospital death (primary outcome) and dialysis (secondary outcome) for patients who developed AKI during hospitalization. A total of 137,084 eligible patients with AKI constitute the analysis set. In the derivation cohort, the area under the receiver operator curve (AUROC) for 24-h, 48-h, 72-h, and 7-day death are 95·05%, 94·23%, 93·53%, and 93·09%, respectively. For dialysis outcome, the AUROC of each time span are 88·32%, 83·31%, 83·20%, and 77·99%, respectively. The predictive performance is consistent in both internal and external validation cohorts. The model can predict important outcomes of patients with AKI, which could be helpful for the early management of AKI.

Extracellular vesicles released by glioma cells are decorated by Annexin A2 allowing for cellular uptake via heparan sulfate.

Extracellular vesicles (EVs) play a crucial role in regulating cell behavior by delivering their cargo to target cells. However, the mechanisms underlying EV-cell interactions are not well understood. Previous studies have shown that heparan sulfate (HS) on target cell surfaces can act as receptors for exosomes uptake, but the ligand for HS on EVs has not been identified. In this study, we isolated EVs from glioma cell lines and glioma patients and identified Annexin A2 (AnxA2) on EVs as a key HS-binding ligand and mediator of EV-cell interactions. Our findings suggest that HS plays a dual role in EV-cell interactions, where HS on EVs captures AnxA2, and on target cells, it acts as a receptor for AnxA2. Removal of HS from the EV surface inhibits EV-target cell interaction by releasing AnxA2. Furthermore, we found that AnxA2-mediated binding of EVs to vascular endothelial cells promotes angiogenesis, and that antibody against AnxA2 inhibited the ability of glioma-derived EVs to stimulate angiogenesis by reducing the uptake of EVs. Our study also suggests that the AnxA2-HS interaction may accelerate the glioma-derived EVs-mediated angiogenesis and that combining AnxA2 on glioma cells with HS on endothelial cells may effectively improve the prognosis evaluation of glioma patients.

Statin initiation and risk of incident kidney disease in patients with diabetes.

BACKGROUND: The role of statin therapy in the development of kidney disease in patients with type 2 diabetes mellitus (DM) remains uncertain. We aimed to determine the relationships between statin initiation and kidney outcomes in patients with type 2 DM. METHODS: Through a new-user design, we conducted a multicentre retrospective cohort study using the China Renal Data System database (which includes inpatient and outpatient data from 19 urban academic centres across China). We included patients with type 2 DM who were aged 40 years or older and admitted to hospital between Jan. 1, 2000, and May 26, 2021, and excluded those with pre-existing chronic kidney disease and those who were already on statins or without follow-up at an affiliated outpatient clinic within 90 days after discharge. The primary exposure was initiation of a statin. The primary outcome was the development of diabetic kidney disease (DKD), defined as a composite of the occurrence of kidney dysfunction (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2 and > 25% decline from baseline) and proteinuria (a urinary albumin-to-creatinine ratio ≥ 30 mg/g and > 50% increase from baseline), sustained for at least 90 days; secondary outcomes included development of kidney function decline (a sustained > 40% decline in eGFR). We used Cox proportional hazards regression to evaluate the relationships between statin initiation and kidney outcomes, as well as to conduct subgroup analyses according to patient characteristics, presence or absence of dyslipidemia, and pattern of dyslipidemia. For statin initiators, we explored the association between different levels of lipid control and outcomes. We conducted analyses using propensity overlap weighting to balance the participant characteristics. RESULTS: Among 7272 statin initiators and 12 586 noninitiators in the weighted cohort, statin initiation was associated with lower risks of incident DKD (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.62-0.83) and kidney function decline (HR 0.60, 95% CI 0.44-0.81). We obtained similar results to the primary analyses for participants with differing patterns of dyslipidemia, those prescribed different statins, and after stratification according to participant characteristics. Among statin initiators, those with intensive control of high-density lipoprotein cholesterol (LDL-C) (< 1.8 mmol/L) had a lower risk of incident DKD (HR 0.51, 95% CI 0.32-0.81) than those with inadequate lipid control (LDL-C ≥ 3.4 mmol/L). INTERPRETATION: For patients with type 2 DM admitted to and followed up in academic centres, statin initiation was associated with a lower risk of kidney disease development, particularly in those with intensive control of LDL-C. These findings suggest that statin initiation may be an effective and reasonable approach for preventing kidney disease in patients with type 2 DM.

Effects of extract solution from magnesium alloys supplemented with different compositions of rare earth elements on in vitro epithelial and osteoblast progenitor cells.

Background: Magnesium alloys (Mg-alloys) have gained significant attention in recent years as a potential bioactive material for clinical applications. The incorporation of rare earth elements (REEs) into Mg-alloys has been of particular interest due to their potential to improve both mechanical and biological properties. Although there are diverse results in terms of cytotoxicity and biological effects of REEs, investigating the physiological benefits of Mg-alloys supplemented with REEs will help in the transition from theoretical to practical applications. Methods: In this study, two culture systems were used to evaluate the effects of Mg-alloys containing gadolinium (Gd), dysprosium (Dy), and yttrium (Y): human umbilical vein endothelial cells (HUVEC) and mouse osteoblastic progenitor cells (MC3T3-E1). Different compositions of Mg-alloys were assessed, and the effects of the extract solution on cell proliferation, viability, and specific cell functions were analyzed. Results: Within the range of weight percentages tested, the Mg-REE alloys did not exhibit any significant negative impacts on either cell line. Interestingly, moderate compositions (Mg-1.5Gd-1.5Dy-0.825Y-0.5Zr and Mg-2Gd-2Dy-1.1Y-0.5Zr) demonstrated a tendency to enhance osteoblastic activity and promote the vascularization process in both HUVEC and MC3T3-E1 cell lines. Discussion: The results of this study provide valuable insights into the potential benefits of REE-supplemented Mg-alloys for clinical applications. The observed enhancement in osteoblastic activity and promotion of vascularization processes suggest that optimizing the compositions of REEs in Mg-alloys could lead to the development of novel, more effective bioactive materials. Further investigations are required to understand the underlying mechanisms and to refine the alloy compositions for improved biocompatibility and performance in clinical settings.

Association between mean arterial pressure and clinical outcomes among patients with heart failure.

AIMS: Mean arterial pressure (MAP) is widely used for evaluating organ perfusion, but its impact on clinical outcomes in patients with heart failure (HF) remains poorly understood. The aim of this study is to investigate the relationship between MAP and all-cause mortality and readmission in patients with HF. METHODS AND RESULTS: We retrospectively analysed data from PhysioNet, involving 2005 patients with HF admitted to Zigong Fourth People's Hospital between 2016 and 2019. The primary outcomes were composite outcomes of all-cause mortality and readmission at 3 and 6 months. The secondary outcomes were readmission at 3 and 6 months. Multivariate-adjusted Cox regression models, restricted cubic spline curves (RCS), and propensity score matching (PSM) were used to explore the relationship between MAP and clinical outcomes. Among 2005 patients with HF [≥70 years, 1460 (72.8%); male, 843 (42.0%)], the incidence of primary outcome at 3 months was 33.4% (223/668), 24.4% (163/668), and 22.7% (152/669), and at 6 months, it was 47.5% (317/668), 38.5% (257/668), and 38.0% (254/669) across MAP tertiles [from Tertile 1 (T1) to Tertile 3 (T3)], respectively. The RCS showed an 'L-shaped' relationship between MAP and primary or secondary endpoints. Multivariate-adjusted Cox models showed that a higher MAP was significantly associated with a lower risk of composite endpoints at 3 months [adjusted hazard ratio (aHR) 0.75, 95% confidence interval (CI) 0.61-0.92, P = 0.006, Tertile 2 (T2); aHR 0.69, 95% CI 0.56-0.86, P = 0.001, T3] and 6 months (aHR 0.79, 95% CI 0.67-0.93, P = 0.005, T2; aHR 0.77, 95% CI 0.64-0.91, P = 0.003, T3) compared with T1. After 1:1 PSM, the effect of maintaining a relatively higher MAP was slightly attenuated. Threshold analyses indicated that per 10 mmHg increase in MAP, there was a 21% and 14% decrease in composite endpoints at 3 and 6 months, respectively (aHR 0.79, 95% CI 0.69-0.91, P = 0.001), and 6 months (aHR 0.86, 95% CI 0.77-0.97, P = 0.013) in patients with MAP ≤ 93 mmHg. The associations were consistent in readmission (secondary outcomes), various subgroups, and sensitivity analysis. CONCLUSIONS: A higher MAP was associated with a lower risk of a composite of all-cause mortality and readmission. Maintaining a relatively higher MAP could potentially improve the clinical prognosis for patients with HF.