Research Progress in Pharmacological Effects and Mechanisms of Angelica sinensis against Cardiovascular and Cerebrovascular Diseases.

Angelica sinensis (Oliv.) Diels (A. sinensis) is a medicinal and edible values substance, which could promote blood circulation and enrich blood. It possesses rich chemical components and nutrients, which have significant therapeutic effects on cardiovascular and cerebrovascular diseases. It is commonly used for the prevention and treatment of cardiovascular and cerebrovascular diseases in the elderly, especially in improving ischemic damage to the heart and brain, protecting vascular cells, and regulating inflammatory reactions. This article reviews the main pharmacological effects and clinical research of A. sinensis on cardiovascular and cerebrovascular diseases in recent years, explores the effect of its chemical components on cardiovascular and cerebrovascular diseases by regulating the expression of functional proteins and inhibiting inflammation, anti-apoptosis, and antioxidant mechanisms. It provides a reference for further research on A. sinensis and the development of related drugs. It provides a new reference direction for the in-depth research and application of A. sinensis in the prevention, improvement, and treatment of cardiovascular and cerebrovascular diseases.

The role of long noncoding ribonucleic acids in the central nervous system injury.

Central nervous system (CNS) injury involves complex pathophysiological molecular mechanisms. Long noncoding ribonucleic acids (lncRNAs) are an important form of RNA that do not encode proteins but take part in the regulation of gene expression and various biological processes. Multitudinous studies have evidenced lncRNAs to have a significant role in the process of progression and recovery of various CNS injuries. Herein, we review the latest findings pertaining to the role of lncRNAs in CNS, both normal and diseased state. We aim to present a comprehensive clinical application prospect of lncRNAs in CNS, and thus, discuss potential strategies of lncRNAs in treating CNS injury.

The cancer-associated fibroblasts related gene CALD1 is a prognostic biomarker and correlated with immune infiltration in bladder cancer.

BACKGROUND: Stromal components of the tumor microenvironment contribute to bladder cancer progression, and Cancer-Associated Fibroblasts (CAFs) were reported to play an important role. Accumulating pieces of evidence indicate that CAFs participate in the crosstalk with tumor cells and have a complex interaction network with immune components. Further studies on the role of CAFs in the bladder cancer microenvironment and searching for possible specific markers are important for a deeper understanding of CAFs in bladder cancer progression and immunomodulation. METHODS: In the present study, we examined the abundance of CAFs in the TCGA and GEO datasets using the MCP-COUNTER algorithm. Additionally, the expression of genes related to CAFs was analyzed through the Weighted Gene Co-expression Network Analysis (WGCNA). The CIBERSORT and ESTIMATE algorithms were used to discuss the correlation of the key CAFs-related gene and the tumor microenvironment components. Immunohistochemistry analysis in clinical samples was used to validate the results of bioinformatics analysis. RESULTS: The results showed that CAFs were closely associated with the progression and prognosis of bladder cancer. WGCNA also revealed that CALD1 was a key CAFs-related gene in bladder cancer. Moreover, further in-depth analysis showed that CALD1 significantly affected the progression and prognosis of bladder cancer. The CIBERSORT and ESTIMATE algorithms demonstrated significant correlations between CALD1 and the tumor microenvironment components, including CAFs, macrophages, T cells, and multiple immune checkpoint related genes. Finally, immunohistochemistry results validated the strong association of CALD1 with CAFs and macrophages. CONCLUSIONS: In the present study, we confirmed the cancer-promoting roles of CAFs in bladder cancer. Being a key gene associated with CAFs, CALD1 may promote bladder cancer progression by remodeling the tumor microenvironment. The bioinformatics methods, including the CIBERSORT, MCP-COUNTER and ESTIMATE algorithms, may provide important value for studying the tumor microenvironment.

Comprehensive analysis of CXCL12 expression reveals the significance of inflammatory fibroblasts in bladder cancer carcinogenesis and progression.

BACKGROUND: Bladder cancer (BLCA) is the most common genitourinary tumor but lacks specific diagnostic biomarkers. Recent years have witnessed significant advances in the use and approval of immune checkpoint blockade (ICB) therapy to manage BLCA at advanced stages when platinum-based therapy has failed. The tumor microenvironment (TME) is essential in impacting BLCA patients' prognosis and responsiveness to ICB therapy. CXCL12 is a stromal secreted factor that was essentially involved in regulating the TME among cancers. In this article, we thoroughly investigated the TME regulating roles of CXCL12 in BLCA and revealed its critical involvement in the development of BLCA, which was closely correlated with inflammatory fibroblasts (iCAFs). METHODS: We examined the gene expression profiles in the TCGA and GEO database to reveal the potential association of CXCL12 with the carcinogenesis and prognosis of BLCA. The receiver operating characteristic curve was used to explore the accuracy of CXCL12 along with multiple iCAFs-associated genes in the diagnosis of BLCA. The MCP-COUNTER, ESTIMATE, and TIDE algorithms were applied to estimate the TME components and predict immunotherapy responsiveness. An iCAFs signature was constructed using the ssGSEA algorithm. The "maftool" R package analyzed the oncogenic mutations in BLCA patients. Bioinformatics analysis results were further validated through immunohistochemistry of clinical samples. IMvigor210 cohort was used to validate bioinformatic predictions of therapeutic responsiveness to immune checkpoint inhibitors. RESULTS: This manuscript revealed a significantly reduced expression of CXCL12 in BLCA compared with normal tissue. The expressions of various marker genes for iCAFs were also reduced considerably in BLCA tissues, highlighting the reduction of iCAFs in the pathogenesis of BLCA. Further studies revealed that CXCL12 and iCAFs were associated with pathological features, TME remodeling and aging in BLCA patients. The iCAFs signature further confirmed the intricate immunomodulatory roles of iCAFs in BLCA. Gene mutation analysis revealed the essential relationship between iCAFs and the mutation frequency of oncogenic genes, including TP53 and FGFR3. Meantimes, iCAFs levels also significantly affected BLCA patients' mutations in the TP53 and RTK-RAS pathways. Finally, our results confirmed the significant exclusion of CD8 + T cells by iCAFs, which further influenced the immunotherapy responsiveness in BLCA patients. CONCLUSIONS: This article highlighted the impact of CXCL12 on the pathogenesis and progression of BLCA. The reduced expression levels of iCAFs markers, including CXCL12, were highly accurate in the diagnosis of BLCA, suggesting the reduction of iCAFs accompanied bladder carcinogenesis. However, both CXCL12 and iCAFs significantly impacted the prognosis and immunotherapy responsiveness for BLCA patients by remodeling the TME. Our results critically suggested the dual roles of iCAFs in the carcinogenesis and progression of BLCA. Further exploration of iCAFs might unravel potential diagnostic biomarkers and therapeutic targets for BLCA.

Curcumin Can Improve Spinal Cord Injury by Inhibiting TGF-ß-SOX9 Signaling Pathway.

Spinal cord injury (SCI) is a severe nervous system disease with high morbidity and disability rate. Signaling pathways play a key role in the neuronal restorative mechanism following SCI. SRY-related high mobility group (HMG)-box gene 9 (SOX9) affects glial scar formation via Transforming growth factor beta (TGF-ß) signaling pathway. Activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is transferred into nucleus to upregulate TGF-ß-SOX9. Curcumin exhibits potent anti-inflammatory and anti-oxidant properties. Curcumin can play an important role in SCI recovery by inhibiting the expression of NF-κB and TGF-ß-SOX9. Herein, we review the potential mechanism of curcumin-inhibiting SOX9 signaling pathway in SCI treatment. The inhibition of NF-κB and SOX9 signaling pathway by curcumin has the potentiality of serving as neuronal regenerative mechanism following SCI.

In-situ remediation of hexavalent chromium contaminated groundwater and saturated soil using stabilized iron sulfide nanoparticles.

Hexavalent chromium (Cr(VI)) is one of prevalent toxic and mobile heavy metal contaminants in the environment. In this study, synthetic iron sulfide nanoparticles (FeS NPs) stabilized with carboxymethyl cellulose (CMC) were applied to remediate Cr(VI) contaminated groundwater and saturated soil. The batch test results showed that aqueous Cr(VI) was removed with a capacity as high as 1046.1 mg Cr(VI) per gram of FeS NPs. The removal of aqueous Cr(VI) mainly involves adsorption, reduction and co-precipitation. Aqueous Cr(VI) removal by using FeS NPs was a strong pH-dependent process. Dissolved oxygen (DO) would compete with Cr(VI) for Fe(II) and S(-II) and inhibit the process of Cr(VI) reduction at pH 5.6. For ionic strength and natural organic matter (NOM), there were no significant influences on the aqueous Cr(VI) removal. Column tests demonstrated that the concentrations of Cr(VI) in the effluent were lower than 0.005 mg L-1 after an elution of 45 pore volumes (PVs) of stabilized FeS NPs suspension. The leached Cr(VI) decreased from 4.58 mg L-1 of raw Cr(VI)-contaminated soil to 46.8-80.7 µg L-1 from the surface to bottom treated soil in column through Toxicity Characteristic Leaching Procedure (TCLP). Therefore, the synthesized FeS NPs hold high potential for the in-situ remediation of Cr(VI)-contaminated groundwater and saturated soil.

Application of transrectal ultrasound-guided repeat needle biopsy in the diagnosis of prostate cancer in Chinese population: A retrospective study.

BACKGROUND: Transrectal ultrasound-guided repeat needle biopsy (TUGRNB) is widely used for diagnosis of prostate cancer (PCa). However, significance of TUGRNB in Chinese population was rarely reported. A retrospective study was conducted to evaluate the significance of TUGRNB applied in prediction of PCa in Chinese population. MATERIALS AND METHODS: A total of 960 from January 2009 to December 2012 were included. Repeat needle biopsy rate and PCa positive detection rate were evaluated. Relationship between prostate specific antigen (PSA) levels and PCa positive rates was analyzed. RESULTS: PCa positive detection rate after initial needle biopsy was 28.4%, which was lower than the rate of repeat needle biopsy (40%). The rate for immediate transurethral resection (TUR), surgery after initial needle biopsy, was 27.1%, however with a low PCa positive detection rate (0.66%). The repeat needle biopsy rate was lower compared with the initial biopsy rate (P < 0.05). Meanwhile, immediate TUR rate was significantly higher than that of the repeat needle biopsy rate (P < 0.05). Among the three groups, the PCa positive detection rate in repeat needle biopsy group was the highest. In subgroups with different PSA levels, the PCa positive rate increased with the elevation of PSA level. In cases with PSA > 20 ng/ml, PCa positive rate was significantly higher than those with PSA < 20 ng/ml (P < 0.05). CONCLUSION: PCa positive detection rate following repeat needle biopsy in Chinese population was higher, although the repeated needle biopsy rate was still in a low level. TUGRNB should attract more attention in the diagnosis of PCa.

Vertical migration in the soil of Cr(VI) and chromite ore processing residue: Field sampling and benchtop simulation.

Chromite ore processing residue (COPR) keeps releasing Cr(VI) over time, and the mixing of residual COPR into soil makes the remediation of COPR-contaminated sites challenging. In this study, a sample of COPR and two soil profiles were collected from a typical historical COPR-contaminated site, and the vertical migration of Cr(VI) and COPR particles in contaminated soil was simulated in the laboratory. Cr(VI) was detected in the upper layer of the field samples at thousands of milligrams per kilogram even after decades of aging, and it can be leached out and migrate vertically deep into the surrounding soil and groundwater. In the COPR-containing soil, more diverse hydrated minerals of brownmillerite were produced than the COPR in the open air on the site. Minerals with high Cr content in COPR-containing soils have a relatively high proportion of particles smaller than 10 µm. COPR particles smaller than 5 µm were found to have migrated downward into the deep soil. During simulated one-year of precipitation, 578.9 mg Cr(VI)/kg was leached from COPR, while 35.5% of the COPR particles smaller than 5 µm had the potential to migrate vertically. The management of COPR particles should be emphasized during risk management or remediation of COPR-contaminated sites.

Superfamily II helicases: the potential therapeutic target for cardiovascular diseases.

Cardiovascular diseases (CVDs) still maintain high morbidity and mortality globally. Helicases, a unique class of enzymes, are extensively implicated in the processes of nucleic acid (NA) metabolism across various organisms. They play a pivotal role in gene expression, inflammatory response, lipid metabolism, and so forth. However, abnormal helicase expression has been associated with immune response, cancer, and intellectual disability in humans. Superfamily II (SFII) is one of the largest and most diverse of the helicase superfamilies. Increasing evidence has implicated SFⅡ helicases in the pathogenesis of multiple CVDs. In this review, we comprehensively review the regulation mechanism of SFⅡ helicases in CVDs including atherosclerosis, myocardial infarction, cardiomyopathies, and heart failure, which will contribute to the investigation of ideal therapeutic targets for CVDs.

Effects of abiotic mineral transformation of FeS on the dynamic immobilization of Cr(VI) in oxic aquatic environments.

Iron sulfide (FeS) can reductively convert soluble Cr(VI) into insoluble Cr(III) under anoxic conditions. However, the fate and transformation of FeS and the stability of immobilized Cr under various oxic environmental conditions are poorly understood. The results show that FeS transforms into pyrrhotite and pyrite intermediates principally and finally lepidocrocite and elemental sulfur, accordingly accounting for 66.1% and 33.9%. Temperature, fulvic acid as natural organic matter and coexisted ions of nitrate, bicarbonate, and calcium affect the evolution of FeS insignificantly. Transformation of FeS involves surface-mediated oxidation of FeS solids, and minor proton-promoted dissolution and oxidation, accompanying synergistic oxidation of Fe(II) and S(-II). Cr(VI) removal performances of oxygenated FeS with increasing duration showed a rise-fall trend. Reduction dominates Cr(VI) uptake first and finally, sorption prevails with the gradual FeS oxygenation. Cr(VI) removal correlates linearly with Cr(VI) reduction, and the reduced Cr species can be predicted based on the known Cr(VI) removal performance. As the FeS oxygenation time increases, newly generated pyrite improves Cr(VI) reduction and removal, and then a decreasing ability to reduce Cr(VI) causes a drop in Cr(VI) removal. These findings provide new insight into the oxidative transformation of FeS in oxic aquatic environments and its impact on Cr(VI) levels.

Corrigendum: The epithelial to mesenchymal transition related gene calumenin is an adverse prognostic factor of bladder cancer correlated with tumor microenvironment remodeling, gene mutation, and ferroptosis.

[This corrects the article DOI: 10.3389/fonc.2021.683951.].

LDL receptor related protein 1 is an adverse prognostic biomarker that correlates with stromal remodeling and macrophages infiltration in bladder cancer.

Introduction: Bladder cancer (BLCA) is a highly heterogeneous disease influenced by the tumor microenvironment, which may affect patients' response to immune checkpoint blockade therapy. Therefore, identifying molecular markers and therapeutic targets to improve treatment is essential. In this study, we aimed to investigate the prognostic significance of LRP1 in BLCA. Methods: We analyzed TCGA and IMvigor210 cohorts to investigate the relationship of LRP1 with BLCA prognosis. We utilized gene mutation analysis and enrichment to identify LRP1-associated mutated genes and biological processes. Deconvolution algorithms and single-cell analysis were used to understand the tumor-infiltrated cells and biological pathways associated with LRP1 expression. Immunohistochemistry was conducted to validate the bioinformatics analysis. Results: Our study revealed that LRP1 was an independent risk factor for overall survival in BLCA patients and was associated with clinicopathological features and FGFR3 mutation frequency. Enrichment analysis demonstrated that LRP1 was involved in extracellular matrix remodeling and tumor metabolic processes. Furthermore, the ssGSEA algorithm revealed that LRP1 was positively correlated with the activities of tumor-associated pathways. Our study also found that high LRP1 expression impaired patients' responsiveness to ICB therapy in BLCA, which was predicted by TIDE prediction and validated by IMvigor210 cohort. Immunohistochemistry confirmed the expression of LRP1 in Cancer-Associated Fibroblasts (CAFs) and macrophages in the tumor microenvironment of BLCA. Discussion: Our study suggests that LRP1 may be a potential prognostic biomarker and therapeutic target in BLCA. Further research on LRP1 may improve BLCA precision medicine and enhance the efficacy of immune checkpoint blockade therapy.

Activation of telomerase by seminal plasma in malignant and normal cervical epithelial cells.

Seminal fluids are involved in the development of cervical cancer but the underlying mechanism is unclear. Because cellular transformation requires telomerase activation by expression of the telomerase reverse transcriptase (hTERT) gene, we examined the role of seminal fluids in telomerase activation. Significantly elevated hTERT mRNA and telomerase activity were observed in cervical cell lines (HeLa, SiHa and Caski) treated with seminal plasma. Normal cervical epithelial cells expressed minimal levels of hTERT mRNA and telomerase activity, and seminal plasma substantially enhanced both expression and activity. The hTERT promoter activity was similarly increased in seminal plasma-treated HeLa cells and this effect was closely correlated with increased Sp1 expression and binding to the hTERT promoter. Cyclooxygenase-2 (COX-2) was simultaneously increased in HeLa cells exposed to seminal plasma, and blockade of COX-2 induction abolished seminal plasma stimulation of the hTERT promoter activity, hTERT expression and telomerase activity. Prostaglandin E2 (PGE2) mimics the effect of seminal plasma, stimulating Sp1 expression, enhancing Sp1 occupancy on the hTERT promoter and promoter activity. Moreover, tumour growth was robustly enhanced when HeLa cells together with seminal plasma were injected into nude-mice. Taken together, seminal plasma stimulates COX-2-PGE2-Sp1-dependent hTERT transcription, which provides insights into the putative mechanism underlying telomerase activation in cervical epithelial and cancer cells.

Jasmonate Positively Regulates Cold Tolerance by Promoting ABA Biosynthesis in Tomato.

As a cold-sensitive species, tomato is frequently challenged by cold stress during vegetative and reproductive growth. Understanding how tomato responds to cold stress is of critical importance for sustainable tomato production. In this work, we demonstrate that jasmonate (JA) plays a crucial role in tomato response to cold stress by promoting abscisic acid (ABA) biosynthesis. It was observed that both JA and ABA levels were substantially increased under cold conditions, whereas the suppression of JA biosynthesis abated ABA accumulation. The ABA biosynthesis gene 9-CIS-EPOXYCAROTENOID DIOXYGENASE2 (NCED2) was subsequently found to be associated with JA-mediated ABA biosynthesis in tomato plants in response to cold stress. NCED2 was rapidly induced by exogenous MeJA and cold treatment. Silencing NCED2 led to a decrease in ABA accumulation that was concurrent with increased cold sensitivity. Moreover, blocking ABA biosynthesis using a chemical inhibitor impaired JA-induced cold tolerance in tomato. Furthermore, MYC2, a core component of the JA signaling pathway, promoted the transcription of NCED2, ABA accumulation and cold tolerance in tomato. Collectively, our results support that JA signaling promotes ABA biosynthesis to confer cold tolerance in tomato.

Effects of omega-3 fatty acid on major cardiovascular outcomes: A systematic review and meta-analysis.

BACKGROUND: The effects of omega-3 fatty acid on cardiovascular health obtained inconsistent results. A systematic review and meta-analysis were therefore conducted to assess the effects of omega-3 fatty acid supplementation for primary and secondary prevention strategies of major cardiovascular outcomes. METHODS: The databases of PubMed, Embase, and the Cochrane library were systematically searched from their inception until September 2020. Relative risks (RRs) with 95% confidence intervals were used to assess effect estimates by using the random-effects model. RESULTS: Twenty-eight randomized controlled trials involving 136,965 individuals were selected for the final meta-analysis. Omega-3 fatty acid was noted to be associated with a lower risk of major cardiovascular events (RR, 0.94; 95% CI, 0.89-1.00; P = .049) and cardiac death (RR, 0.92; 95% CI, 0.85-0.99; P = .022). However, no significant differences was noted between omega-3 fatty acid and the control for the risks of all-cause mortality (RR, 0.97; 95% CI, 0.92-1.03; P = .301), myocardial infarction (RR, 0.90; 95% CI, 0.80-1.01; P = .077), and stroke (RR, 1.02; 95% CI, 0.94-1.11; P = .694). CONCLUSIONS: Major cardiovascular events and cardiac death risks could be avoided with the use of omega-3 fatty acid. However, it has no significant effects on the risk of all-cause mortality, myocardial infarction, and stroke.

Dynamic Changes in Myofibroblasts Affect the Carcinogenesis and Prognosis of Bladder Cancer Associated With Tumor Microenvironment Remodeling.

Bladder cancer (BLCA) is a tumor that possesses significant heterogeneity, and the tumor microenvironment (TME) plays an important role in the development of BLCA. The TME chiefly consists of tumor cells and tumor-infiltrating immune cells admixed with stromal components. Recent studies have revealed that stromal components, especially cancer-associated fibroblasts (CAFs), affect immune cell infiltration and modulate the extracellular matrix in the TME of BLCA, ultimately impacting the prognosis and therapeutic efficacy of BLCA. Among the subgroups of CAFs, myofibroblasts (myCAFs) were the most abundant and were demonstrated to play an essential role in affecting the prognosis of various tumors, including BLCA. However, the dynamic changes in myCAFs during carcinogenesis and tumor progression have been less discussed previously. With the help of bioinformatics algorithms, we discussed the roles of myCAFs in the carcinogenesis and prognosis of BLCA in this manuscript. Our study highlighted the pathogenesis of BLCA was accompanied by a decrease in the abundance of myCAFs, revealing potential protective properties of myCAFs in the carcinogenesis of BLCA. Meanwhile, the reduced expressions of myCAFs marker genes were highly accurate in predicting tumorigenesis. In contrast, we also demonstrated that myCAFs regulated extracellular matrix remodeling, tumor metabolism, cancer stemness, and oncological mutations, ultimately impacting the treatment responsiveness and prognosis of BLCA patients. Thus, our research revealed the bimodal roles of myCAFs in the development of BLCA, which may be associated with the temporal change of the TME. The in-depth study of myofibroblasts and the TME may provide potential diagnostic biomarkers and therapeutic targets for BLCA.

Single-Cell Sequencing of Malignant Ascites Reveals Transcriptomic Remodeling of the Tumor Microenvironment during the Progression of Epithelial Ovarian Cancer.

Epithelial ovarian cancer (EOC) is the main cause of mortality among gynecological malignancies worldwide. Although patients with EOC undergo aggregate treatment, the prognosis is often poor. Peritoneal malignant ascites is a distinguishable clinical feature in EOC patients and plays a pivotal role in tumor progression and recurrence. The mechanisms of the tumor microenvironment (TME) in ascites in the regulation of tumor progression need to be explored. We comprehensively analyzed the transcriptomes of 4680 single cells from five EOC patients (three diagnostic samples and two recurrent samples) derived from Gene Expression Omnibus (GEO) databases. Batch effects between different samples were removed using an unsupervised deep embedding single-cell cluster algorithm. Subcluster analysis identified the different phenotypes of cells. The transition of a malignant cell state was confirmed using pseudotime analysis. The landscape of TME in malignant ascites was profiled during EOC progression. The transformation of epithelial cancer cells into mesenchymal cells was observed to lead to the emergence of related anti-chemotherapy and immune escape phenotypes. We found the activation of multiple biological pathways with the transition of tumor-associated macrophages and fibroblasts, and we identified the infiltration of CD4+CD25+ T regulatory cells in recurrent samples. The cell adhesion molecules mediated by integrin might be associated with the formation of the tumorsphere. Our study provides novel insights into the remodeling of the TME heterogeneity in malignant ascites during EOC progression, which provides evidence for identifying novel therapeutic targets and promotes the development of ovarian cancer treatment.

Appraising the Causal Association between Systemic Iron Status and Heart Failure Risk: A Mendelian Randomisation Study.

Although observational studies have shown that abnormal systemic iron status is associated with an increased risk of heart failure (HF), it remains unclear whether this relationship represents true causality. We aimed to explore the causal relationship between iron status and HF risk. Two-sample Mendelian randomisation (MR) was applied to obtain a causal estimate. Genetic summary statistical data for the associations (p < 5 × 10−8) between single nucleotide polymorphisms (SNPs) and four iron status parameters were obtained from the Genetics of Iron Status Consortium in genome-wide association studies involving 48,972 subjects. Statistical data on the association of SNPs with HF were extracted from the UK biobank consortium (including 1088 HF cases and 360,106 controls). The results were further tested using MR based on the Bayesian model averaging (MR-BMA) and multivariate MR (MVMR). Of the twelve SNPs considered to be valid instrumental variables, three SNPs (rs1800562, rs855791, and rs1799945) were associated with all four iron biomarkers. Genetically predicted iron status biomarkers were not causally associated with HF risk (all p > 0.05). Sensitivity analysis did not show evidence of potential heterogeneity and horizontal pleiotropy. Convincing evidence to support a causal relationship between iron status and HF risk was not found. The strong relationship between abnormal iron status and HF risk may be explained by an indirect mechanism.

Exploring the Causal Effects of Circulating ST2 and Galectin-3 on Heart Failure Risk: A Mendelian Randomization Study.

Background: Heart failure (HF), primarily caused by conditions such as coronary heart disease or cardiomyopathy, is a global health problem with poor prognosis and heavy burden on healthcare systems. As biomarkers of myocardial injury and fibrosis, suppression of tumorigenicity 2 (ST2) and galectin-3 were recommended for prognosis stratification in HF guidelines. However, the causality between these two mediators and HF remains obscure. This study aimed to explore the causal relationship of genetically determined ST2 and galectin-3 with the risk of HF. Methods: We used the two-sample Mendelian randomization (MR) method, incorporating available genome-wide association summary statistics, to investigate the causal association of ST2 and galectin-3 with HF risk. We applied inverse-variance weighted analysis as the main method of analysis. Results: In our final MR analysis, 4 single-nucleotide polymorphisms (SNPs) of ST2 and galectin-3, respectively, were identified as valid instrumental variables. Fixed-effect inverse variance weighted (IVW) analysis indicated that genetically predicted ST2 and galectin-3 were not causally associated with HF risk 3. [odds ratio (OR) = 0.9999, 95% confidence interval [CI] = 0.9994-1.0004, p = 0.73; OR = 1.0002, 95% CI = 0.9994-1.0010, p = 0.60, respectively]. These findings were robust in sensitivity analyses, including MR-Egger regression and leave-one-out analysis. Conclusion: This MR study provided no evidence for the causal effects of ST2 and galectin-3 on HF risk.

Predicting the Prognosis of Patients in the Coronary Care Unit: A Novel Multi-Category Machine Learning Model Using XGBoost.

Background: Early prediction and classification of prognosis is essential for patients in the coronary care unit (CCU). We applied a machine learning (ML) model using the eXtreme Gradient Boosting (XGBoost) algorithm to prognosticate CCU patients and compared XGBoost with traditional classification models. Methods: CCU patients' data were extracted from the MIMIC-III v1.4 clinical database, and divided into four groups based on the time to death: <30 days, 30 days-1 year, 1-5 years, and ≥5 years. Four classification models, including XGBoost, naïve Bayes (NB), logistic regression (LR), and support vector machine (SVM) were constructed using the Python software. These four models were tested and compared for accuracy, F1 score, Matthews correlation coefficient (MCC), and area under the curve (AUC) of the receiver operating characteristic curves. Subsequently, Local Interpretable Model-Agnostic Explanations method was performed to improve XGBoost model interpretability. We also constructed sub-models of each model based on the different categories of death time and compared the differences by decision curve analysis. The optimal model was further analyzed using a clinical impact curve. At last, feature ablation curves of the XGBoost model were conducted to obtain the simplified model. Results: Overall, 5360 CCU patients were included. Compared to NB, LR, and SVM, the XGBoost model showed better accuracy (0.663, 0.605, 0.632, and 0.622), micro-AUCs (0.873, 0.811, 0.841, and 0.818), and MCC (0.337, 0.317, 0.250, and 0.182). In subgroup analysis, the XGBoost model had a better predictive performance in acute myocardial infarction subgroup. The decision curve and clinical impact curve analyses verified the clinical utility of the XGBoost model for different categories of patients. Finally, we obtained a simplified model with thirty features. Conclusions: For CCU physicians, the ML technique by XGBoost is a potential predictive tool in patients with different conditions, and it may contribute to improvements in prognosis.