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Estimated pulse wave velocity (ePWV) has been found to be an independent predictor of cardiovascular mortality and kidney injury, which can be estimated noninvasively. This study aimed to investigate the association between ePWV and in-hospital mortality in critically ill patients with acute kidney injury (AKI). This study included 5960 patients with AKI from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The low and high ePWV groups were compared using a Kaplan-Meier survival curve to evaluate the differences in survival status. Cox proportional hazards models were used to explore the association between ePWV and in-hospital mortality in critically ill patients with AKI. To further examine the dose-response relationship, we used a restricted cubic spline (RCS) model. Stratification analyses were conducted to investigate the effect of ePWV on hospital mortality across various subgroups. Survival analysis indicated that patients with high ePWV had a lower survival rate than those with low ePWV. Following adjustment, high ePWV demonstrated a statistically significant association with an increased risk of in-hospital mortality among AKI patients (HR = 1.53, 95% CI = 1.36-1.71, p < 0.001). Analysis using the RCS model confirmed a linear increase in the risk of hospital mortality as the ePWV values increased (P for nonlinearity = 0.602). A high ePWV was significantly associated with an increased risk of in-hospital mortality among patients with AKI. Furthermore, ePWV was an independent predictor of in-hospital mortality in critically ill patients with AKI. [ABSTRACT FROM AUTHOR]

BACKGROUND: This study focused on circulating plasma protein profiles to identify mediators of hypertension-driven myocardial remodeling and heart failure. METHODS: A Mendelian randomization design was used to investigate the causal impact of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure on 82 cardiac magnetic resonance traits and heart failure risk. Mediation analyses were also conducted to identify potential plasma proteins mediating these effects. RESULTS: Genetically proxied higher SBP, DBP, and pulse pressure were causally associated with increased left ventricular myocardial mass and alterations in global myocardial wall thickness at end diastole. Elevated SBP and DBP were linked to increased regional myocardial radial strain of the left ventricle (basal anterior, mid, and apical walls), while higher SBP was associated with reduced circumferential strain in specific left ventricular segments (apical, mid-anteroseptal, mid-inferoseptal, and mid-inferolateral walls). Specific plasma proteins mediated the impact of blood pressure on cardiac remodeling, with FGF5 (fibroblast growth factor 5) contributing 2.96% (P =0.024) and 4.15% (P =0.046) to the total effect of SBP and DBP on myocardial wall thickness at end diastole in the apical anterior segment and leptin explaining 15.21% (P =0.042) and 23.24% (P =0.022) of the total effect of SBP and DBP on radial strain in the mid-anteroseptal segment. Additionally, FGF5 was the only mediator, explaining 4.19% (P =0.013) and 4.54% (P =0.032) of the total effect of SBP and DBP on heart failure susceptibility. CONCLUSIONS: This mediation Mendelian randomization study provides evidence supporting specific circulating plasma proteins as mediators of hypertension-driven cardiac remodeling and heart failure. [ABSTRACT FROM AUTHOR]

Background: It is unknown whether D2 lymphadenectomy + complete mesogastric excision for gastric cancer improves survival compared with just D2 lymphadenectomy. Methods: Between September 2014 and June 2018, patients with advanced gastric cancer were randomly assigned (1 : 1) to laparoscopic D2 lymphadenectomy or D2 lymphadenectomy + complete mesogastric excision gastrectomy. The modified intention-to-treat population was defined as patients who had pathologically confirmed gastric adenocarcinoma (pT1 N1–3 M0 and pT2–4 N0–3 M0). The primary endpoint was 3-year disease-free survival. Secondary endpoints were the recurrence pattern and overall survival. Results: The median follow-up of patients in the D2 lymphadenectomy group (169 patients) and patients in the D2 lymphadenectomy +complete mesogastric excision group (169 patients) was 55 (interquartile range 37–60) months and 51 (interquartile range 40–60) months respectively. Recurrence occurred in 50 patients in the D2 lymphadenectomy group (29.6%) versus 33 patients in the D2 lymphadenectomy + complete mesogastric excision group (19.5%) (P = 0.032). The 3-year disease-free survival was 75.5% (95% c.i. 68.3% to 81.3%) in the D2 lymphadenectomy group versus 85.0% (95% c.i. 78.7% to 89.6%) in the D2 lymphadenectomy + complete mesogastric excision group (log rank P = 0.042). The HR for recurrence in the D2 lymphadenectomy + complete mesogastric excision group versus the D2 lymphadenectomy group was 0.64 (95% c.i. 0.41 to 0.99) by Cox regression (P = 0.045). The 3-year overall survival rate was 77.5% (95% c.i. 70.4% to 83.1%) in the D2 lymphadenectomy group versus 85.8% (95% c.i. 79.6% to 90.2%) in the D2 lymphadenectomy + complete mesogastric excision group (log rank P = 0.058). The HR for death in the D2 lymphadenectomy + complete mesogastric excision group versus the D2 lymphadenectomy group was 0.64 (95% c.i. 0.41 to 1.02) (P = 0.058). Conclusion: Compared with conventional D2 dissection, D2 lymphadenectomy + complete mesogastric excision is associated with better disease-free survival, but there is no statistically significant difference in overall survival. Registration number: NCT01978444 (http://www.clinicaltrials.gov). Compared with conventional D2 dissection, D2 + complete mesogastric excision shows favourable oncological outcomes in curable advanced gastric cancer. [ABSTRACT FROM AUTHOR]

Introduction: Acute pulmonary embolism (APE) is a typical cardiovascular emergency worldwide. Mean hemoglobin concentration (MCHC) is a standard indicator of anemia. Studies on the association between MCHC and APE are scarce. We aimed to investigate the relationship between MCHC and APE. Methods: Clinical data were extracted from the Medical Information Bank for Intensive Care (MIMIC)-III. Adult (≥18 years) patients with APE admitted for the first time were included in this study. An analysis was conducted to evaluate the association between MCHC and the prognosis of patients by the Cox regression analysis, generalized additives models and Kaplan–Meier survival curves. The primary outcome was 30-day mortality, and the secondary outcomes were 1-year and 3-year mortality. Results: A total of 813 patients who met the selection criteria were enrolled, of whom 130 (16.0%) died within 30 days of admission. Univariate Cox regression indicated that MCHC was significantly associated with mortality (30-day: HR = 0.74, 95% CI = 0.66–0.82, P < 0.001; 1-year: HR = 0.80, 95% CI = 0.74–0.86, P < 0.001; 3-year: HR = 0.82, 95% CI = 0.77–0.88, P < 0.001). MCHC remains stable after adjusting multiple models. Kaplan-Meier survival curves showed that patients with lower MCHC had a poorer 30-day prognosis. Conclusions: Lower MCHC is an independent risk factor for increased mortality in patients with APE. As an inexpensive biomarker, MCHC should receive more attention. [ABSTRACT FROM AUTHOR]

AbstractCardiovascular disease (CVD) is one of the leading causes of death globally, and vascular calcification (VC) has been recognized as an independent and strong predictor of global CVD and mortality. Chronic inflammation has been demonstrated to play a significant role in the progression of VC. This review aims to summarize the literature that aimed to elucidate the associations between dietary inflammation (DI) and VC as well as to explore the mechanisms underlying the association and discuss strategies (including dietary interventions) to prevent VC. Notably, diets rich in processed foods, carbohydrates with high glycemic index/load, saturated fatty acids, trans-fatty acids, cholesterol, and phosphorus were found to induce inflammatory responses and accelerate the progression of VC, indicating a close relationship between DI and VC. Moreover, we demonstrate that an imbalance in the composition of the gut microbiota caused by the intake of specific dietary choices favored the production of certain metabolites that may contribute to the progression of VC. The release of inflammatory and adhesion cytokines, activation of inflammatory pathways, oxidative stress, and metabolic disorders were noted to be the main mechanisms through which DI induced VC. To reduce and slow the progression of VC, emphasis should be placed on the intake of diets rich in omega-3 fatty acids, dietary fiber, Mg, Zn, and polyphenols, as well as the adjustment of dietary pattern to reduce the risk of VC. This review is expected to be useful for guiding future research on the interplay between DI and VC. [ABSTRACT FROM AUTHOR]

A novel gene called LAPTM4B (lysosome-associated protein transmembrane 4 beta) plays several crucial roles in carcinogenesis. In this case-control study, we investigated the relationship between LAPTM4B gene polymorphism and susceptibility to endometrial carcinoma (EC). In an adjusted multivariate logistic regression analyses, subjects with the LAPTM4B*1/2 and *2/2 genotypes respectively exhibited 1.572-fold (95% confidence interval (CI) = 1.041-2.375) and 2.335-fold (95% CI = 1.365-3.995) increases in the risk of developing EC relative to those carrying LAPTM4B*1/1. Patients with LAPTM4B *2 had both significantly shorter overall survival (OS) and shorter disease-free survival (DFS) (both p < 0.001). Multivariate analysis showed that LAPTM4B genotype is an independent prognostic factor for OS and DFS (both p < 0.001). These results suggest that LAPTM4B polymorphisms might play an important role in the aetiology of EC. [ABSTRACT FROM AUTHOR]

Background: Carotid-femoral pulse wave velocity has been identified as an autonomous predictor of cardiovascular mortality and kidney injury. This important clinical parameter can be non-invasively estimated using the calculated pulse wave velocity (ePWV). The objective of this study was to examine the correlation between ePWV and in-hospital as well as one-year mortality among critically ill patients with chronic kidney disease (CKD) and atherosclerotic heart disease (ASHD)., Methods: This study included a cohort of 1173 patients diagnosed with both CKD and ASHD, sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The four groups divided into quartiles according to ePWV were compared using a Kaplan-Meier survival curve to assess variations in survival rates. Cox proportional hazards models were employed to analyze the correlation between ePWV and in-hospital as well as one-year mortality among critically ill patients with both CKD and ASHD. To further investigate the dose-response relationship, a restricted cubic splines (RCS) model was utilized. Additionally, stratification analyses were performed to examine the impact of ePWV on hospital and one-year mortality across different subgroups., Results: The survival analysis results revealed a negative correlation between higher ePWV and survival rate. After adjusting for confounding factors, higher ePWV level (ePWV > 11.90 m/s) exhibited a statistically significant association with an increased risk of both in-hospital and one-year mortality among patients diagnosed with both CKD and ASHD (HR = 4.72, 95% CI = 3.01-7.39, p  < 0.001; HR = 2.04, 95% CI = 1.31-3.19, p  = 0.002). The analysis incorporating an RCS model confirmed a linear escalation in the risk of both in-hospital and one-year mortality with rising ePWV values ( P for nonlinearity = 0.619; P for nonlinearity = 0.267)., Conclusions: The ePWV may be a potential marker for the in-hospital and one-year mortality assessment of CKD with ASHD, and elevated ePWV was strongly correlated with an elevated mortality risk in patients diagnosed with both CKD and ASHD.

Objective: Quanzhen Yiqi decoction (QZYQ) is a traditional Chinese medicine for treating chronic obstructive pulmonary disease., Methods: Mice were exposed to cigarette smoke (CS) 6 days/week (40 cigarettes/day) for 24 weeks and then intragastrically administered QZYQ (4.72, 9.45, or 18.89 g/kg) or dexamethasone (DEX, 0.6 mg/kg) for 6 weeks. We examined the lung function and collected bronchoalveolar lavage fluid for inflammatory cell and cytokine quantification. The pathological lung changes, ROS and oxidative biomarkers were measured. We used immunohistochemistry and western blotting to evaluate the levels of Nrf2/HO-1, NLRP3/ASC/Caspase1/IL-1β/IL-18., Results: The CS group showed significant increases in the forced vital capacity, lung resistance, and chord compliance and a lower FEV50/FVC compared with the control, and QZYQ improved these changes. In addition, QZYQ effectively reduced emphysema, immune cell infiltration, and airway remodeling. QZYQ stimulated HO-1 expression and reduced oxidative stress through the Nrf2 pathway. QZYQ inhibited the production of NLRP3/ASC/Caspase-1 to inhibit IL-1β and IL-18., Conclusion: Our study suggested that QZYQ can improve the function and histology of the lungs and reduce inflammatory cell recruitment. QZYQ inhibits ROS production and NLRP3 inflammasome activation by upregulating Nrf2 to reduce lung injury. The anti-inflammatory effects of QZYQ are similar to those of DEX., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background/aim: Depression has become a multiple disease worldwide, and is closely related to the systemic inflammatory response., Methods: Based on the data of the National Health and Nutrition Examination Survey (NHANES), this study included 2,514 depressive and 26,487 non-depressive adults. The systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) were used to quantify systemic inflammation. The multivariate logistic regression and inverse probability weighting methods were used to analyze the effect size of SII and SIRI on the risk of depression., Results: After adjusting for all confounders, the above associations of SII and SIRI with depression risk remained significant (SII, OR = 1.02, 95% CI = 1.01 to 1.02, p = 0.001; SIRI, OR = 1.06, 95% CI = 1.01 to 1.10, p = 0.016). Each 100-unit increase in SII was associated with a 2% increase in the risk of depression, while each one-unit increase in SIRI was associated with a 6% increase in the risk of depression., Conclusion: Systemic inflammatory biomarkers (SII and SIRI) significantly affected the risk of depression. SII or SIRI can serve as a biomarker of anti-inflammation treatment for depression., 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 © 2023 Li, Huan, Lin and Hu.)

Background/aim: Optimized dietary patterns have been considered an important determinant of delaying aging in cardiometabolic disease (CMD). Dietary pattern with high-level dietary inflammatory potential is a key risk factor for cardiometabolic disease, and has drawn increasing attention. The aim of this study was to investigate whether dietary pattern with high dietary inflammatory potential was associated with aging acceleration in cardiometabolic disease., Materials and Methods: We analyzed the cross-sectional data from six survey cycles (1999-2000, 2001-2002, 2003-2004, 2005-2006, 2007-2008, and 2009-2010) of the National Health and Nutritional Examination Surveys (NHANES). A total of 16,681 non-institutionalized adults and non-pregnant females with CMD were included in this study. Dietary inflammatory index (DII) was used to assess the dietary inflammatory potential. The two age acceleration biomarkers were calculated by the residuals from regressing chronologic age on Klemera-Doubal method biological age (KDM BioAge) or Phenotypic Age (PhenoAge), termed "KDMAccel" and "PhenoAgeAccel." A multivariable linear regression accounting for multistage survey design and sampling weights was used in different models to investigate the association between DII and aging acceleration. Four sensitivity analyses were used to ensure the robustness of our results. Besides, we also analyzed the anti-aging effects of DASH-type dietary pattern and "Life's Simple 7"., Results: For 16,681 participants with CMD, compared with the first tertile of DII after adjusting for all potential confounders, the patients with second tertile of DII showed a 1.02-years increase in KDMAccel and 0.63-years increase in PhenoAgeAccel (KDMAccel, β = 1.02, 95% CI = 0.64 to 1.41, P < 0.001; PhenoAgeAccel, β = 0.63, 95% CI = 0.44 to 0.82, P < 0.001), while the patients with the third tertile of DII showed a 1.48-years increase in KDMAccel and 1.22-years increase in PhenoAgeAccel (KDMAccel, β = 1.48, 95% CI = 1.02 to 1.94, P < 0.001; PhenoAgeAccel, β = 1.22, 95% CI = 1.01 to 1.43, P < 0.001). In addition, DASH-type dietary pattern was associated with a 0.57-years reduction in KDMAccel (β = -0.57, 95% CI = -1.08 to -0.06, P = 0.031) and a 0.54-years reduction in PhenoAgeAccel (β = -0.54, 95% CI = -0.80 to -0.28, P < 0.001). The each one-unit increase in CVH score was associated with a 1.58-years decrease in KDMAccel (β = -1.58, 95% CI = -1.68 to -1.49, P < 0.001) and a 0.36-years in PhenoAgeAccel (β = -0.36, 95% CI = -0.41 to -0.31, P < 0.001)., Conclusion: Among CMD, the dietary pattern with high dietary inflammatory potential was association with aging acceleration, and the anti-aging potential of DASH-type dietary pattern and "Life's Simple 7" should also be given attention, but these observations require future prospective validation., 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 Hu, Wang, Huan, Zhang, Lin, Li and Li.)

Background: Tripartite motif-containing protein 44 ( TRIM44 ) was recently identified as a novel oncogene that is overexpressed in several types of human cancers. However, the biological functions of TRIM44 in epithelial ovarian cancer (EOC) remain unclear. Here, we aimed to investigate the role of TRIM44 in EOC and its clinical implications., Methods: TRIM44 was knocked down using shRNA transfection. In vitro proliferation, invasion, migration and apoptosis of ovarian cancer (OC) cells were detected by CCK8, colony formation assay, Transwell inserts and flow cytometry analysis. The growth ability of xenograft tumors was examined in vivo in a nude mouse metastatic tumor model. Finally, we performed gene chip analysis and ingenuity pathway analysis (IPA) to analyze the potential gene network., Results: High expression of TRIM44 was observed in EOC tissues. Knockdown of TRIM44 expression substantially suppressed the proliferation, migration, invasion and colony-forming ability of EOC cells in vitro and attenuated tumor growth in vivo . Mechanistic studies revealed that silencing TRIM44 dramatically downregulated the expression of FOXM1 , EZH2 , CCNE2 , CCND3 and BIRC5 in EOC cells, at least in part through inactivation of the FOXM1-EZH2 signaling pathway., Conclusions: Collectively, these data suggest that downregulation of TRIM44 inhibits the progression of EOC through suppression of the FOXM1-EZH2 signaling pathway. These results provide novel insight into the role of TRIM44 in tumorigenesis and suggest that it could be a potential therapeutic target for ovarian carcinoma., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-21-2915/coif). All authors report that this work was supported by grants of Heilongjiang Provincial Natural Science Foundation of China (No. LH2020H124); the Liande Wu Science Foundation for Young Scholars of Harbin Medical University Cancer Hospital (No. WLD-QN1705); the Jingying Foundation of the Harbin Medical University Cancer Hospital (No. JY2015-04); The Medical Award Foundation Project of Beijing (No. YXJL-2021-0577-0421); and The Science and Technology Innovation Medical Development Foundation Project of Beijing (No. KC2021-JF-0055-01). The authors have no other conflicts of interest to declare., (2022 Translational Cancer Research. All rights reserved.)

Background/Aim: Several observational studies showed a significant association between elevated iron status biomarkers levels and sepsis with the unclear direction of causality. A two-sample bidirectional mendelian randomization (MR) study was designed to identify the causal direction between seven iron status traits and sepsis. Methods: Seven iron status traits were studied, including serum iron, ferritin, transferrin saturation, transferrin, hemoglobin, erythrocyte count, and reticulocyte count. MR analysis was first performed to estimate the causal effect of iron status on the risk of sepsis and then performed in the opposite direction. The multiplicative random-effects and fixed-effects inverse-variance weighted, weighted median-based method and MR-Egger were applied. MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO), and Cochran's Q statistic methods were used to assess heterogeneity and pleiotropy. Results: Genetically predicted high levels of serum iron (OR = 1.21, 95%CI = 1.13-1.29, p = 3.16 × 10 -4 ), ferritin (OR = 1.32, 95%CI = 1.07-1.62, p =0.009) and transferrin saturation (OR = 1.14, 95%CI = 1.06-1.23, p = 5.43 × 10 -4 ) were associated with an increased risk of sepsis. No significant causal relationships between sepsis and other four iron status biomarkers were observed. Conclusions: This present bidirectional MR analysis suggested the causal association of the high iron status with sepsis susceptibility, while the reverse causality hypothesis did not hold. The levels of transferrin, hemoglobin, erythrocytes, and reticulocytes were not significantly associated with sepsis. Further studies will be required to confirm the potential clinical value of such a prevention and treatment strategy., 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 Hu, Cheng, Mao, Chen, Cui and Qiu.)

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a disease with high heterogeneity, which is a major challenge in clinical individualized treatment. A mucus phenotype is one of the main characteristics of COPD. MATERIAL AND METHODS Gene expression profiles of lung tissue samples were from the Lung Genomics Research Consortium. MUC5B-associated gene signatures were obtained based on a nonlinear feature screening algorithm. These signatures were used to fit a latent profile analysis (LPA) model to identify COPD molecular subtypes and build a subtype classifier to verify the subtypes. Then, we explored the characteristics of cilium assembly and beating signatures, transcriptome features, immune infiltration among the 3 subtypes by xCell, single-sample gene set enrichment analysis, network perturbation amplitude, and weighted gene co-expression network analysis algorithms. An external dataset was used to verify the above COPD subtypes. RESULTS Three subtypes associated with mucus were identified by LPA and verified in an external dataset. Subtype 1 displayed higher T helper type 1 (Th1) and basophil infiltration, higher Th17/regulatory T cells (Tregs) ratio, a higher level of cilium assembly and beating, and lower mast cell and Treg infiltration. The subtypes 2 and 3 demonstrated higher macrophage M2 infiltration in lung tissue, while subtype 3 had higher neutrophil and eosinophil infiltration than subtype 2. CONCLUSIONS Overall, this work identified 3 mucus-associated molecular subtypes related to MUC5B expression, which deepens the understanding of airway mucus secretion in COPD and potentially provides valuable information for precision therapy.