A precise blood transfusion evaluation model for aortic surgery: a single-center retrospective study.

Cardiac aortic surgery is an extremely complicated procedure that often requires large volume blood transfusions during the operation. Currently, it is not possible to accurately estimate the intraoperative blood transfusion volume before surgery. Therefore, in this study, to determine the clinically precise usage of blood for intraoperative blood transfusions during aortic surgery, we established a predictive model based on machine learning algorithms. We performed a retrospective analysis on 4,285 patients who received aortic surgery in Beijing Anzhen Hospital between January 2018 and September 2022. Ultimately, 3,654 patients were included in the study, including 2,557 in the training set and 1,097 in the testing set. By utilizing 13 current mainstream models and a large-scale cardiac aortic surgery dataset, we built a novel machine learning model for accurately predicting intraoperative red blood cell transfusion volume. Based on the transfusion-related risk factors that the model identified, we also established the relevant variables that affected the results. The results revealed that decision tree models were the most suitable for predicting the blood transfusion volume during aortic surgery. In particular, the mean absolute error for the best-performing extremely randomized forest model was 1.17 U, while the R2 value was 0.50. Further exploration into intraoperative blood transfusion during aortic surgery identified erythrocytes, estimated operation duration, body weight, sex, red blood cell count, and D-dimer as the six most significant risk factors. These factors were subsequently analyzed for their influence on intraoperative blood transfusion volume in relevant patients, as well as the protective threshold for prediction. The novel intraoperative blood transfusion prediction model for cardiac aorta surgery in this study effectively assists clinicians in accurately calculating blood transfusion volumes and achieving effective utilization of blood resources. Furthermore, we utilize interpretability technology to reveal the influence of critical risk factors on intraoperative blood transfusion volume, which provides an important reference for physicians to provide timely and effective interventions. It also enables personalized and precise intraoperative blood usage.

Comprehensive transcriptomic analyses identify KDM genes-related subtypes with different TME infiltrates in gastric cancer.

Histone lysine demethylases (KDMs) have been reported in various malignances, which affect transcriptional regulation of tumor suppressor or oncogenes. However, the relationship between KDMs and formation of tumor microenvironment (TME) in gastric cancer (GC) remain unclear and need to be comprehensively analyzed.In the present study, 24 KDMs were obtained and consensus molecular subtyping was performed using the "NMF" method to stratify TCGA-STAD into three clusters. The ssGSEA and CIBERSORT algorithms were employed to assess the relative infiltration levels of various cell types in the TME. The KDM_score was devised to predict patient survival outcomes and responses to both immunotherapy and chemotherapy.Three KDM genes-related molecular subtypes were Figured out in GC with distinctive clinicopathological and prognostic features. Based on the robust KDM genes-related risk_score and nomogram, established in our work, GC patients' clinical outcome can be well predicted. Furthermore, low KDM genes-related risk_score exhibited the more effective response to immunotherapy and chemotherapy.This study characterized three KDM genes-related TME pattern with unique immune infiltration and prognosis by comprehensively analyses of transcriptomic profiling. Risk_score was also built to help clinicians decide personalized anticancer treatment for GC patients, including in prediction of immunotherapy and chemotherapy response for patients.

Metformin Ameliorates Postoperative Cognitive Dysfunction through Regulation of the AMPK/SIRT1 Pathway.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common postoperative complication in elderly patients. The purpose of this study was to investigate the mechanism through which metformin improves postoperative cognitive function. METHODS: In the in vivo experiment, 18-month-old Sprague-Dawley (SD) rats were randomly divided into four groups (n = 12 in each group): the control, metformin, operation, and operation plus metformin groups. The animals were pretreated with metformin by gavage once daily for two weeks. The Morris water maze (MWM) was used to measure cognitive ability. In the in vitro experiment, BV2 cells were divided into five groups: the control, metformin, lipopolysaccharide (LPS), LPS plus metformin, and LPS plus metformin plus compound C groups. We stimulated microglia with LPS (500 ng/mL). Immunofluorescence and Western blotting were used to assess ROS (reactive oxygen species) levels, autophagy-associated protein levels and adenosine monophosphate-activated protein kinase (AMPK)/regulator factor 2-related enzyme 1 (SIRT1) signaling pathway activity in the rat cortex and microglial cells. RESULTS: In the MWM test, the metformin-pretreated rats spent a higher proportion of time in the target quadrant. Immunofluorescence showed that the fluorescence intensity of LC3 in the cortex was increased in rats pretreated with metformin. Western blotting indicated that metformin upregulated the expression of autophagy-related and AMPK/SIRT1 signaling pathway-related proteins in the cortex after surgery. By activating the AMPK/SIRT1 signaling pathway in vitro, metformin reduced microglial activation and oxidative stress and promoted autophagy. CONCLUSIONS: Through the AMPK/SIRT1 pathway, metformin can boost autophagy and reduce oxidative stress in cortical microglia in older rats, in turn improving postoperative cognitive function.

Bulk and single-cell transcriptome profiling reveal necroptosis-based molecular classification, tumor microenvironment infiltration characterization, and prognosis prediction in colorectal cancer.

BACKGROUND: Necroptosis is a new form of programmed cell death that is associated with cancer initiation, progression, immunity, and chemoresistance. However, the roles of necroptosis-related genes (NRGs) in colorectal cancer (CRC) have not been explored comprehensively. METHODS: In this study, we obtained NRGs and performed consensus molecular subtyping by "ConsensusClusterPlus" to determine necroptosis-related subtypes in CRC bulk transcriptomic data. The ssGSEA and CIBERSORT algorithms were used to evaluate the relative infiltration levels of different cell types in the tumor microenvironment (TME). Single-cell transcriptomic analysis was performed to confirm classification related to NRGs. NRG_score was developed to predict patients' survival outcomes with low-throughput validation in a patients' cohort from Fudan University Shanghai Cancer Center. RESULTS: We identified three distinct necroptosis-related classifications (NRCs) with discrepant clinical outcomes and biological functions. Characterization of TME revealed that there were two stable necroptosis-related phenotypes in CRC: a phenotype characterized by few TME cells infiltration but with EMT/TGF-pathways activation, and another phenotype recognized as immune-excluded. NRG_score for predicting survival outcomes was established and its predictive capability was verified. In addition, we found NRCs and NRG_score could be used for patient or drug selection when considering immunotherapy and chemotherapy. CONCLUSIONS: Based on comprehensive analysis, we revealed the potential roles of NRGs in the TME, and their correlations with clinicopathological parameters and patients' prognosis in CRC. These findings could enhance our understanding of the biological functions of necroptosis, which thus may aid in prognosis prediction, drug selection, and therapeutics development.

Human umbilical cord mesenchymal stem cell-derived exosomes attenuate neuroinflammation and oxidative stress through the NRF2/NF-κB/NLRP3 pathway.

AIMS: We investigated whether human umbilical cord mesenchymal stem cell (hUC-MSC)-derived exosomes bear therapeutic potential against lipopolysaccharide (LPS)-induced neuroinflammation. METHODS: Exosomes were isolated from hUC-MSC supernatant by ultra-high-speed centrifugation and characterized by transmission electron microscopy and western blotting. Inflammatory responses were induced by LPS in BV-2 cells, primary microglial cultures, and C57BL/6J mice. H2 O2 was also used to induce inflammation and oxidative stress in BV-2 cells. The effects of hUC-MSC-derived exosomes on inflammatory cytokine expression, oxidative stress, and microglia polarization were studied by immunofluorescence and western blotting. RESULTS: Treatment with hUC-MSC-derived exosomes significantly decreased the LPS- or H2 O2 -induced oxidative stress and expression of pro-inflammatory cytokines (IL-6 and TNF-α) in vitro, while promoting an anti-inflammatory (classical M2) phenotype in an LPS-treated mouse model. Mechanistically, the exosomes increased the NRF2 levels and inhibited the LPS-induced NF-κB p65 phosphorylation and NLRP3 inflammasome activation. In contrast, the reactive oxygen species scavenger NAC and NF-κB inhibitor BAY 11-7082 also inhibited the LPS-induced NLRP3 inflammasome activation and switched to the classical M2 phenotype. Treatment with the NRF2 inhibitor ML385 abolished the anti-inflammatory and anti-oxidative effects of the exosomes. CONCLUSION: hUC-MSC-derived exosomes ameliorated LPS/H2 O2 -induced neuroinflammation and oxidative stress by inhibiting the microglial NRF2/NF-κB/NLRP3 signaling pathway.

Dexmedetomidine promotes colorectal cancer progression via Piwil2 signaling.

PURPOSE: α2-adrenoceptor agonist dexmedetomidine (DEX) has been reported to promote tumorigenesis. Stem-cell protein Piwil2 is associated with cancer progression. Whether Piwil2 plays a role in tumor-promoting effects of DEX is unknown. METHODS: We examined the expression of Piwil2 in human colorectal cancer (CRC) cell lines with/without DEX treatment. We also studied the roles of Piwil2 in proliferation, invasion, migration, as well as expressions of epithelial-mesenchymal transition (EMT)-related proteins in DEX-treated in vitro and in vivo CRC models. And the experiments with genetic and pharmacological treatments were conducted to investigate the underlying molecular mechanism. RESULTS: RNA-sequencing (RNA-seq) analysis found Piwil2 is one of most upregulated genes upon DEX treatment in CRC cells. Furthermore, Piwil2 protein levels significantly increased in DEX-treated CRC cancer cells, which promoted proliferation, invasion, and migration in both CRC cell lines and human tumor xenografts model. Mechanistically, DEX increased nuclear factor E2-related factor 2 (Nrf2) expression, which enhanced Piwil2 transcription via binding to its promoter. Furthermore, in vitro experiments with Piwil2 knockdown or Siah2 inhibition indicated that DEX promoted EMT process and tumorigenesis through Siah2/PHD3/HIF1α pathway. The experiments with another α2-adrenoceptor agonist Brimonidine and antagonists yohimbine and atipamezole also suggested the role of Piwil2 signaling in tumor-promoting effects via an α2 adrenoceptor-dependent manner. CONCLUSION: DEX promotes CRC progression may via activating α2 adrenoceptor-dependent Nrf2/Piwil2/Siah2 pathway and thus EMT process. Our work provides a novel insight into the mechanism underlying tumor-promoting effects of α2-adrenoceptor agonists.

CCR5 antagonist maraviroc alleviates doxorubicin-induced neuroinflammation and neurobehavioral deficiency by regulating NF-κB/NLRP3 signaling in a breast cancer mouse model.

The chemotherapeutic agent Doxorubicin (DOX) is known to cause chemotherapy-induced cognitive impairment (CICI). Maraviroc, a potent C-C chemokine receptor 5 (CCR5) antagonist, shows neuroprotective properties, while its role in CICI remains unclear. This study determined the therapeutic potential of maraviroc on CICI. Adult C57BL/6J mice with implanted breast cancer cells received four weekly intraperitoneal injections of saline (Control group), 5 mg/kg DOX (DOX group), 10 mg/kg maraviroc (MVC group), or 5 mg/kg DOX with 10 mg/kg maraviroc (DOX + MVC group). The Morris Water Maze (MWM) was used for neurobehavioural test. Western blot analysis and immunofluorescence were used to evaluate the expressions of inflammatory markers, apoptosis-related proteins, and synaptic-related proteins. The volume and weight of tumor were also evaluated after treatments. DOX treatment significantly increased chemokines (CCL3, CCL4) and inflammatory cytokines (IL-1ß, TNF-α) in tumor-bearing mice hippocampus. While maraviroc administration reduced hippocampal proinflammatory factors compared to the DOX group. Furthermore, it also lowered apoptosis markers, restored synaptic proteins levels, and inhibited the NF-κB/NLRP3 pathway. Accordingly, maraviroc treatment significantly improved DOX-induced neurobehavioural impairments as evidenced by an increased number of platform crossings and percentage of target quadrant time in the MWM test. Additionally, when combined with DOX, maraviroc had additional inhibitory effects on tumor growth. These findings suggest that maraviroc can mitigate DOX-induced CICI by suppressing elevated proinflammatory chemokines and cytokines through the NF-κB/NLRP3 pathway, potentially offering an anti-tumor benefit. This research presents a promising therapeutic approach for DOX-induced CICI, enhancing the safety and efficacy of cancer treatments.

Prognosis of unresected versus resected early-stage pulmonary carcinoid tumors ≤3 cm in size: A population-based study.

PURPOSE: The observation-based prognosis, rather than resection, for small carcinoid tumors is still unclear. This lack of clarity has important implications for counseling elderly patients or patients for whom surgical resection poses a high risk. This study compared the outcomes of observation and surgical resection in patients with pulmonary carcinoid (PC) tumors ≤3 cm in size without metastasis. METHODS: Data of patients with PC tumors with ≤3 cm in diameter and without lymph node and distant metastases were retrieved from Surveillance, Epidemiology, and End Results (SEER) registry. To reduce the inherent bias of retrospective studies, propensity score matching analysis was performed. Overall survival (OS) and lung carcinoid-specific survival (LCSS) were analyzed using Kaplan-Meier plots. Multivariate analysis was used to determine predictors of LCSS in different size subgroups. RESULTS: In total, 4552 patients with early-stage PCs ≤3 cm in diameter, including 435 (9.56%) who were observed and 4117 (90.44%) treated by surgery, were recruited. Patients with surgery had significantly better OS and LCSS than those who were observed. However, patients with observation had comparable LCSS to those with surgery for PCs with tumor diameters ≤1 cm. Multivariate analysis indicated that surgical resection was an independent prognostic factor for LCSS in 1 cm < tumors ≤2 cm, and 2 cm < tumors ≤3 cm groups, but not for tumors ≤1 cm in diameter. CONCLUSION: Surgical resection of small PCs is associated with a survival advantage over observation. However, for early PCs ≤1 cm in diameter, observation may be considered in patients with high risk for surgical resection.

Topological Embedding of Human Brain Networks with Applications to Dynamics of Temporal Lobe Epilepsy.

We introduce a novel, data-driven topological data analysis (TDA) approach for embedding brain networks into a lower-dimensional space in quantifying the dynamics of temporal lobe epilepsy (TLE) obtained from resting-state functional magnetic resonance imaging (rs-fMRI). This embedding facilitates the orthogonal projection of 0D and 1D topological features, allowing for the visualization and modeling of the dynamics of functional human brain networks in a resting state. We then quantify the topological disparities between networks to determine the coordinates for embedding. This framework enables us to conduct a coherent statistical inference within the embedded space. Our results indicate that brain network topology in TLE patients exhibits increased rigidity in 0D topology but more rapid flections compared to that of normal controls in 1D topology.

Emerging non-proinflammatory roles of microglia in healthy and diseased brains.

Microglia, the resident myeloid cells of the central nervous system, are the first line of defense against foreign pathogens, thereby confining the extent of brain injury. However, the role of microglia is not limited to macrophage-like functions. In addition to proinflammatory response mediation, microglia are involved in neurodevelopmental remodeling and homeostatic maintenance in the absence of disease. An increasing number of studies have also elucidated microglia-mediated regulation of tumor growth and neural repair in diseased brains. Here, we review the non-proinflammatory roles of microglia, with the aim of promoting a deeper understanding of the functions of microglia in healthy and diseased brains and contributing to the development of novel therapeutics that target microglia in neurological disorders.

Methylene blue targets PHD3 expression in murine microglia to mitigate lipopolysaccharide-induced neuroinflammation and neurocognitive impairments.

Methylene blue (MB) has anti-inflammatory properties, however, its underlying molecular mechanism remains elusive. This study aimed to investigate whether and how MB could attenuate lipopolysaccharide (LPS)-induced microglial activation, neuroinflammation, and neurobehavioral deficits. We measured the expression of pro-inflammatory factors and performed three neurobehavioral tests to assess the effect of MB on neuroinflammation and neurocognitive dysfunction in LPS-treated adult C57BL/6N male mice or LPS-stimulated microglia cells. In vitro and in vivo experiments were further performed to investigate the molecular mechanism underlying MB inhibition of neuroinflammation using various experimental methods, including western blot, RT-qPCR, immunofluorescence, seahorse measurement, positron emission tomography (PET) scan, and flow cytometry analyses. Our results demonstrated that microglial activation and M1 polarization were induced by LPS exposure, resulting in an inflammatory response and neuronal apoptosis. Furthermore, LPS induced metabolic reprogramming in microglial cells. However, MB treatment substantially inhibited LPS-induced elevated levels of pro-inflammatory factors and reversed metabolic activation in vivo, which eventually led to the resolution of neuroinflammation and neurobehavioral improvement. Mechanistically, MB specifically inhibited the LPS-induced overexpression of PHD3 in vitro and in vivo. The pharmacological and genetic manipulations unveiled that the Siah2/Morg1/PHD3 signaling pathway may mediate MB protection against LPS-induced neuroinflammation and neurotoxicity. Therefore MB inhibited PHD3-dependent neuroinflammation may via Siah2/Morg1/PHD3 pathway, and that PHD3 expressed in microglia may be a drug target for the treatment of neuroinflammation-related brain disorders.

A Retrospective Study of the Relationship Between Blood Transfusion and 30-Day Postoperative Outcomes in Patients Undergoing Isolated Off-Pump Coronary Artery Bypass Grafting.

INTRODUCTION: The objective of this single-center study it to retrospectively analyze the relationship between transfusion and 30-day postoperative outcomes in patients undergoing isolated off-pump coronary artery bypass grafting. METHODS: Perioperative data of 2,178 patients who underwent isolated off-pump coronary artery bypass grafting from 2018 to 2019 were collected. A 1:1 propensity score matching was performed to control for potential biases between patients who received blood transfusion and those who did not. After propensity score matching, we analyzed the clinical outcomes of transfusion and non-transfusion patients. Postoperative complications and the survival of patients within 30 days after surgery in both groups were analyzed. Kaplan-Meier survival curve and log-rank test were used for survival analysis. RESULTS: The total blood transfusion rate of all patients was 29%, including red blood cell (27.6%), plasma (7.3%), and platelet (1.9%). Four hundred and forty patients in each group were compared after propensity score matching. There were no significant differences in the incidence of stroke, myocardial infarction, atrial fibrillation, acute kidney function injury, and sternal wound infection of both groups (P>0.05). However, higher incidence of postoperative pulmonary infection and more mechanical ventilation time and days of stay in the intensive care unit and postoperative in-hospital stay were associated with blood transfusion (P<0.05). The 30-day cumulative survival rate of the transfusion group was lower than that of the control group (P<0.05). CONCLUSION: Perioperative blood transfusion increases the risks of postoperative pulmonary infection and short-term mortality in off-pump coronary artery bypass grafting patients.

A prospective randomized controlled study on scheduled PDE5i and vacuum erectile devices in the treatment of erectile dysfunction after nerve sparing prostatectomy.

Cavernous nerve injury is an important cause of erectile dysfunction (ED). Although protective nerve technology has been widely used in nerve-sparing radical prostatectomy (nsRP), the incidence of ED is still very high after surgery. The purpose of our study was to evaluate erectile function (EF) and penile length in the non-erectile state (PLNES) following scheduled phosphodiesterase 5 inhibitor (PDE5i), vacuum erectile device (VED) treatment, and combination therapy after nsRP. One hundred patients with localized prostate cancer and normal EF were randomized to scheduled PDE5i group, VED treatment group, a combined treatment group, and the control group without any intervention. The International Index of Erectile Function-5 (IIEF-5) scores and PLNES were evaluated after 6 months and 12 months of treatment. Sexual Encounter Profile (SEP-Question 2 and SEP-Question 3) were evaluated after 12 months of treatment. Ninety-one of the 100 randomized patients completed the study. We found that the 5 mg tadalafil once a day (OaD) combined with VED can help improve IIEF-5 scores in nsRP patients after both 6 months and 12 months. VED alone or combined with tadalafil OaD can help patients maintain PLNES. VED combined with tadalafil OaD can improve the rate of successful penetration (SEP-Question 2) after 12 months. There were no significant differences in the return to target EF after 12 months among the groups. No significant correlation was noted between the variables and return to target EF (IIEF ≥ 17), and between the variables and effective shortening of the patient's penis (shortening ≥ 1 cm) after 12 months of intervention.

Near-infrared light-triggered polypyrrole promotes C2C12 cell differentiation and inhibits TNF-α induced myotube atrophy.

Treatment of skeletal muscle atrophy and strengthening the muscles remain a challenge in modern medicine. Studies have shown that photobiomodulation can inhibit skeletal muscle atrophy and aid in functional recovery. Near-infrared radiation (NIR) therapy has emerged as a complementary therapy for the treatment of skeletal muscle atrophy, but its underlying mechanism remains unclear. Polypyrrole (PPy) is an organic polymer with strong near-infrared absorption, which can generate heat from absorbed NIR. In this study, MHC immunofluorescence staining was performed on C2C12 myoblasts to investigate the differentiation of C2C12 cells after NIR-triggered PPy exposure. As TNF-α-induced C2C12 myotubes were used as a model of muscular atrophy. Giemsa staining was used to determine the myotube diameter. Western blot analysis was performed to examine the proteins involved in the differentiation and atrophy of muscle cells, as well as in the Akt/P70S6K signaling pathway. PPy triggered by NIR promoted the differentiation of C2C12 cells, inhibited C2C12 myotube atrophy caused by TNF-α, and downregulated the expression levels of Atrogin-1 and MuRF 1 protein. In addition, we determined that Akt/P70S6K signaling pathway activity plays a crucial role in the therapeutic effect of NIR-triggered polypyrrole, which was further confirmed by the administration of the Akt inhibitor GDC0068. The optimal conditions for these effects were a PPy concentration of 0.125 mg/ml and NIR exposure for 80 s. We show that the photothermal effect of PPy triggered by near-infrared light can increase the beneficial effects of NIR, promote the differentiation of C2C12 cells, and improve C2C12 myotube atrophy, laying a foundation for its future clinical use.

[Chymase, a product of mast cell activation, is the main mediator in angiogenesis in mouse matrigel plugs].

Objective To investigate the role of mast cell activation products in promoting angiogenesis. Methods SD rat peritoneal mast cells (RPMC) were isolated and activated by calcium ionophore. The activation products were extracted and the activity of chymase was detected. Thirty BALB/c mice were randomly divided into a control group, an activation product group, and an inhibitor group (10 mice in each group), and the angiogenisis of mast cell activation products was studied by matrigel plug assay. In the matrigel plug, the hemoglobin (Hb) concentration was determined by hemiglobincyanide (HiCN) method, the distribution of blood vessels was observed by HE staining, and the microvessel density (MVD) was detected by CD34 immunohistochemical staining. Results The activity of chymase was detected in the activation products of isolated RPMCs. The results of mice matrigel plug assay showed that the Hb level in matrigel plug of the activation product group was about 7 times higher than that of the control group, while the Hb level of the inhibitor group was 80.8% lower than that of the activation product group. HE staining showed new blood vessels in the matrigel plug of the activation product group, and some vascular lumens were observed. The results of MVD showed that the MVD in matrigel plug of the activation product group was about 5 times than that of the control group, while MVD of the inhibitor group was 66.2% lower than that of the activation product group. Conclusion Chymase, a product of mast cell activation, is the main mediator to promote angiogenesis in mouse matrigel plugs.

Early-senescent bone marrow mesenchymal stem cells promote C2C12 cell myogenic differentiation by preventing the nuclear translocation of FOXO3.

AIMS: Mouse bone marrow mesenchymal stem cells (BMSCs) are pluripotent cells with self-renewal and differentiation abilities. Since the effects of senescent BMSCs on C2C12 cells are not fully clear, the present study aimed to elucidate these effects. MAIN METHODS: Senescence-associated ß-galactosidase staining and western blotting were performed to confirm the senescence of BMSCs. Immunofluorescence and western blotting were used to assess myoblast differentiation in each group. The role of the AKT/P70 signaling pathway and forkhead box O3 (FOXO3) nuclear translocation was explored by western blotting. BMSC-derived exosomes were injected into the tibialis anterior of mice, and RT-qPCR was used to assess the role of exosomes in promoting muscle differentiation. KEY FINDINGS: Conditioned medium (CM) from early-senescent BMSCs promoted myogenic differentiation in vitro, which was detected as enhanced expression of myosin heavy chain (MHC), myogenin (MYOG), and myogenic differentiation 1 (MyoD). The AKT signaling pathway was found to be regulated by CM, which inhibited FOXO3 nuclear translocation. RT-qPCR analysis results showed that MHC, MyoD, and MYOG mRNA expression increased in the tibialis anterior of mice after exosome injection. SIGNIFICANCE: The present study demonstrated that early-senescent BMSCs accelerated C2C12 cell myogenic differentiation, and the transcription factor, FOXO3, was the target of senescent cells. Collectively, our results suggest that the AKT/P70 signaling pathway mediates the effect of BMSCs on neighboring cells.

MiR-1290 promotes myoblast differentiation and protects against myotube atrophy via Akt/p70/FoxO3 pathway regulation.

BACKGROUND: Sarcopenia is a common skeletal disease related to myogenic disorders and muscle atrophy. Current clinical management has limited effectiveness. We sought to investigate the role of miR-1290 in myoblast differentiation and muscle atrophy. METHODS: By transfecting miR-1290 into C2C12 cells, we investigated whether miR-1290 regulates myogenesis and myotube atrophy via AKT/P70 signaling pathway. MHC staining was performed to assess myoblast differentiation. Differentiation-related MHC, Myod, and Myog protein levels, and atrophy-related MuRF1 and atrogin-1 were explored by western blot. An LPS-induced muscle atrophy rat model was developed. RT-PCR was conducted to analyze miR-1290 serum levels in muscle atrophy patients and normal controls (NCs). RESULTS: The miR-1290 transfection increased MHC-positive cells and MHC, Myod, and Myog protein levels in the miR-1290 transfection group, demonstrating that miR-1290 promoted C2C12 myoblast differentiation. Myotube diameter in the miR-1290 transfection group was higher than in the TNF-α-induced model group. Western blot analysis showed decreased MuRF1 and atrogin-1 levels in the miR-1290 transfection group compared with the model group, demonstrating that miR-1290 protected against myoblast cellular atrophy. Luciferase assay and western blot analysis showed that miR-1290 regulation was likely caused by AKT/p70/FOXO3 phosphorylation activation. In the LPS-induced muscle atrophy rat model, miR-1290 mimics ameliorated gastrocnemius muscle loss and increased muscle fiber cross-sectional area. Clinically, miR-1290 serum level was significantly decreased in muscle atrophy patients. CONCLUSIONS: We found that miR-1290 enhances myoblast differentiation and inhibits myotube atrophy through Akt/p70/FoxO3 signaling in vitro and in vivo. In addition, miR-1290 may be a potential therapeutic target for sarcopenia treatment.

Adjusted preoperative variables to predict perioperative red blood cell transfusion in coronary artery bypass grafting.

BACKGROUND: The variables for predicting blood transfusion perioperatively are not completely clear in coronary artery bypass grafting (CABG) patients. OBJECTIVES: To construct a comprehensive model to predict perioperative RBC transfusion in patients undergoing isolated CABG using adjusted preoperative variables. METHODS: Perioperative data of 1253 patients who underwent isolated CABG by the same surgical team were collected from April 2018 to March 2019. Logistic regression analyses were used to establish equations to construct two models for predicting intraoperative and postoperative RBC transfusions, respectively. All significant variables included in the two models were combined to form a comprehensive model to predict perioperative RBC transfusion. Area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the discriminatory power of the models. RESULTS: The total RBC transfusion rate for CABG patients during hospitalization was 29.05%. The rate of intraoperative and postoperative RBC transfusions was 6.9% and 26.7%, respectively. Eight variables in a total of 30 risk factors constituted the intraoperative prediction model, 12 variables constituted the postoperative prediction model, and 13 variables for the combined model. The AUC of the three models were 0.87, 0.82, and 0.83, respectively, demonstrating moderate discriminatory power for RBC transfusion during the intraoperative, postoperative, and perioperative periods. CONCLUSION: The comprehensive model combined with all variables of predicting intraoperative and postoperative RBC transfusion is feasible for predicting perioperative RBC transfusion.

A Retrospective Study of the Relationship Between Blood Transfusion and 30-Day Postoperative Outcomes in Patients Undergoing Isolated Off-Pump Coronary Artery Bypass Grafting

ABSTRACT Introduction: The objective of this single-center study it to retrospectively analyze the relationship between transfusion and 30-day postoperative outcomes in patients undergoing isolated off-pump coronary artery bypass grafting. Methods: Perioperative data of 2,178 patients who underwent isolated off-pump coronary artery bypass grafting from 2018 to 2019 were collected. A 1:1 propensity score matching was performed to control for potential biases between patients who received blood transfusion and those who did not. After propensity score matching, we analyzed the clinical outcomes of transfusion and non-transfusion patients. Postoperative complications and the survival of patients within 30 days after surgery in both groups were analyzed. Kaplan-Meier survival curve and log-rank test were used for survival analysis. Results: The total blood transfusion rate of all patients was 29%, including red blood cell (27.6%), plasma (7.3%), and platelet (1.9%). Four hundred and forty patients in each group were compared after propensity score matching. There were no significant differences in the incidence of stroke, myocardial infarction, atrial fibrillation, acute kidney function injury, and sternal wound infection of both groups (P>0.05). However, higher incidence of postoperative pulmonary infection and more mechanical ventilation time and days of stay in the intensive care unit and postoperative in-hospital stay were associated with blood transfusion (P<0.05). The 30-day cumulative survival rate of the transfusion group was lower than that of the control group (P<0.05). Conclusion: Perioperative blood transfusion increases the risks of postoperative pulmonary infection and short-term mortality in off-pump coronary artery bypass grafting patients.

[Pollution Characteristics and Potential Ecological Risk of Heavy Metals in Urban Surface Water Sediments from Yongkang].

In order to understand the pollution characteristics of heavy metals in surface water sediments of Yongkang, we analyzed the concentrations of 10 heavy metals including Ti, Cr, Mn, Co, Ni, Cu, Zn, As, Pb and Fe in 122 sediment samples, explored the underlying source of heavy metals and then assessed the potential ecological risks of those metals by methods of the index of geo-accumulation and the potential ecological risk. The study results showed that: 10 heavy metal contents followed the order: Fe > Ti > Mn > Zn > Cr > Cu > Ph > Ni > As > Co, all heavy metals except for Ti were 1. 17 to 3.78 times higher than those of Zhejiang Jinhua- Quzhou basin natural soils background values; The concentrations of all heavy metals had a significantly correlation between each other, indicating that those heavy metals had similar sources of pollution, and it mainly came from industrial and vehicle pollutions; The pollution extent of heavy metals in sediments by geo-accumulation index (Igeo) followed the order: Cr > Zn > Ni > Cu > Fe > As > Pb >Mn > Ti, thereinto, Cr, Zn, Cu and Ni were moderately polluted or heavily polluted at some sampling sites; The potential ecological risk of 9 heavy metals in sediments were in the following order: Cu > As > Ni > Cr > Pb > Co > Zn > Mn > Ti, Cu and As contributed the most to the total potential ecological risk, accounting for 22.84% and 21. 62% , others had a total of 55.54% , through the ecological risk assessment, 89. 34% of the potential ecological risk indexes ( RI) were low and 10. 66% were higher. The contamination level of heavy metals in Yongkang was slight in total, but was heavy in local areas.