TGF-ß1 induced activations of Smad2 and miRNAs inhibit SF-1- and LRH-1-dependent CYP19 expression in rat Leydig cells†.

P450 aromatase, encoded by the Cyp19 gene, catalyzes the synthesis of estrogen, which is crucial for mammalian germ cell differentiation. We have previously shown that transforming growth factor beta 1 (TGF-ß1) attenuated the accumulation of steroidogenic factor-1 (SF-1) and liver receptor homolog-1 (LRH-1) and eventually reduced the transcription of Cyp19 in rat Leydig cells (LCs). Here, we report that TGF-ß1 treatment-induced phosphorylation of Smad2 and decreased the expression levels of SF-1 and LRH-1 by elevating the expression levels of microRNA-21-3p and microRNA-339-5p in vivo and in vitro. Furthermore, both TGF-ß1 treatment and over-expression of Smad2 inhibited the SF-1 or LRH-1-regulated promoter activity of the Cyp19 gene, and p-Smad2 physically interacted with SF-1 and LRH-1. Our findings collectively suggest that TGF-ß1 may inhibit the expression of CYP19 in LCs mainly through two ways. On the one hand, TGF-ß1 acts through Smad2 to repress the accumulation of SF-1 and LRH-1 at post-transcriptional level by upregulating specific microRNAs. On the other hand, TGF-ß1 inhibits the transcriptional activity of Cyp19 through the interaction of p-Smad2 with SF-1/LRH-1.

Expression and Biochemical Characterization of a Novel Marine Chitosanase from Streptomyces niveus Suitable for Preparation of Chitobiose.

It is known that bioactivities of chitooligosaccharide (COS) are closely related to the degree of polymerization (DP); therefore, it is essential to prepare COS with controllable DP, such as chitobiose showing high antioxidant and antihyperlipidemia activities. In this study, BLAST, sequence alignment and phylogenetic analysis of characterized glycoside hydrolase (GH) 46 endo-chitosanases revealed that a chitosanase Sn1-CSN from Streptomyces niveus was different from others. Sn1-CSN was overexpressed in E. coli, purified and characterized in detail. It showed the highest activity at pH 6.0 and exhibited superior stability between pH 4.0 and pH 11.0. Sn1-CSN displayed the highest activity at 50 °C and was fairly stable at ≤45 °C. Its apparent kinetic parameters against chitosan (DDA: degree of deacetylation, >94%) were determined, with Km and kcat values of 1.8 mg/mL and 88.3 s-1, respectively. Cu2+ enhanced the activity of Sn1-CSN by 54.2%, whereas Fe3+ inhibited activity by 15.1%. Hydrolysis products of chitosan (DDA > 94%) by Sn1-CSN were mainly composed of chitobiose (87.3%), whereas partially acetylated chitosan with DDA 69% was mainly converted into partially acetylated COS with DP 2-13. This endo-chitosanase has great potential to be used for the preparation of chitobiose and partially acetylated COS with different DPs.

Blood-Brain Barrier Permeable Chitosan Oligosaccharides Interfere with ß-Amyloid Aggregation and Alleviate ß-Amyloid Protein Mediated Neurotoxicity and Neuroinflammation in a Dose- and Degree of Polymerization-Dependent Manner.

It is proven that ß-amyloid (Aß) aggregates containing cross-ß-sheet structures led to oxidative stress, neuroinflammation, and neuronal loss via multiple pathways. Therefore, reduction of Aß neurotoxicity via inhibiting aggregation of Aß or dissociating toxic Aß aggregates into nontoxic forms might be effective therapeutic methods for Alzheimer's disease (AD) treatment. This study was designed to explore interference of chitosan oligosaccharides (COS) on ß-(1-42)-amyloid protein (Aß42) aggregation and Aß42-induced cytotoxicity. Here it was demonstrated that COS showed good blood-brain barrier (BBB) penetration ability in vitro and in vivo. The experimental results showed that COS efficiently interfered with Aß42 aggregation in dose- and degree of polymerization (DP)-dependent manners, and COS monomer with DP6 showed the best effect on preventing conformational transition into ß-sheet-rich structures. Based on the binding affinity analysis by microscale thermophoresis (MST), it was confirmed that COS could directly bind with Aß42 in a DP-dependent manner. Our findings demonstrated that different performance of COS monomers with different DPs against Aß42 assembly was, to some extent, attributable to their different binding capacities with Aß42. As a result, COS significantly ameliorated Aß42-induced cytotoxicity. Taken together, our studies would point towards a potential role of COS in treatment of AD.

Chitosan Oligosaccharides Coupling Inhibits Bacterial Biofilm-Related Antibiotic Resistance against Florfenicol.

The formation of bacterial biofilms has increased the resistance of bacteria to various environmental factors and is tightly associated with many persistent and chronic bacterial infections. Herein we design a strategy conjugating florfenicol, an antibiotic commonly used in the treatment of streptococcus, with the antimicrobial biomaterial, chitosan oligosaccharides. The results demonstrated that the florfenicol-COS conjugate (F-COS) efficiently eradicated the mature Streptococcus hyovaginalis biofilm, apparently inhibiting drug resistance to florfenicol. A quantity of 250 µg/mL F-COS showed effective inhibitory activity against planktonic cells and biofilm of the bacteria, and a 4-fold improvement of the F-COS compared to unmodified florfenicol was observed. Furthermore, the conjugate showed a broad-spectrum activity against both Gram-positive and Gram-negative bacteria. It suggested that F-COS might have a potential for application in the treatment of biofilm-related infections.

Synthesis and Evaluation of a Chitosan Oligosaccharide-Streptomycin Conjugate against Pseudomonas aeruginosa Biofilms.

Microbial biofilms are considerably more resistant to antibiotics than planktonic cells. It has been reported that chitosan coupling with the aminoglycoside antibiotic streptomycin dramatically disrupted biofilms of several Gram-positive bacteria. This finding suggested the application of the covalent conjugate of antimicrobial natural polysaccharides and antibiotics on anti-infection therapy. However, the underlying molecular mechanism of the chitosan-streptomycin conjugate (CS-Strep) remains unclear and the poor water-solubility of the conjugate might restrict its applications for anti-infection therapy. In this study, we conjugated streptomycin with water-soluble chitosan oligosaccharides (COS). Unlike CS-Strep, the COS-streptomycin conjugate (COS-Strep) barely affected biofilms of tested Gram-positive bacteria. However, COS-Strep efficiently eradicated established biofilms of the Gram-negative pathogen Pseudomonas aeruginosa. This activity of COS-Strep was influenced by the degree of polymerization of chitosan oligosaccharide. The increased susceptibility of P. aeruginosa biofilms to antibiotics after conjugating might be related to the following: Suppression of the activation of MexX-MexY drug efflux pump system induced by streptomycin treatment; and down-regulation of the biosynthesis of biofilm exopolysaccharides. Thus, this work indicated that covalently linking antibiotics to chitosan oligosaccharides was a possible approach for the development of antimicrobial drugs against biofilm-related infections.

Detection of Hb A2 and Hb Constant Spring (HBA2: c.427T>C) by Capillary Electrophoresis in a Patient with Hb H-Hb CS Disease.

Hb A2 (α2δ2) is one of the key components looked for in hemoglobinopathies screening programs. Therefore, quantitative and accurate method for Hb A2 value determination is essential for routine screening. Here, we report a case of Hb A2 and Hb Constant Spring (Hb CS, HBA2: c.427T>C) with Hb H-Hb CS disease that was not detected by high performance liquid chromatography (HPLC), while Hb A2 and Hb CS were clearly quantified by capillary electrophoresis (CE).

Protective effects of polydatin on experimental testicular torsion and detorsion injury in rats.

Oxidative stress plays a critical role in the process of testicular torsion and detorsion (T/D). The purpose of the present study was to investigate the protective effect of polydatin (PD) on testicular T/D injury. Rats were randomly divided into three groups, a sham group, a group subjected to 2h torsion followed by 24h detorsion and a group subjected to T/D and injected i.p. with 20mgkg-1 PD 30min before detorsion. Unilateral orchiectomy was performed after 24h of reperfusion. Half the testes were prepared for histological examination by haematoxylin-eosin staining and the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) technique. In the remaining tissues, levels of malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) were determined, as was the expression of several apoptosis-related proteins. Compared with the T/D group, PD pretreatment significantly ameliorated the morphological damage, lowered the Cosentino histological score and increased the mean number of germ cell layers and Johnsen's testicular biopsy score. In addition, PD treatment markedly decreased MDA levels and upregulated CAT, GPx and SOD activity. Furthermore, PD decreased T/D-induced germ cell-specific apoptosis, attenuated the activation of caspase-3, caspase-8, caspase-9 and poly(ADP-ribose) polymerase and increased the Bcl-2/Bax ratio. The findings indicate that PD has a protective effect against testicular T/D injuries, especially at the histological, antioxidative stress and antiapoptotic levels.

Different locations of RANTES and its receptors on mouse epididymal spermatozoa.

Our previous study showed that the chemokine regulated upon activation normal T-cell expressed and secreted (RANTES) originating from the mouse epididymis bound to the midpiece of luminal spermatozoa. The present study was undertaken to investigate the association between RANTES and epididymal spermatozoa and to determine whether the association is mediated by the RANTES receptors CCR1, CCR3 or CCR5. The use of reverse transcription polymerase chain reaction (RT-PCR), immunohistochemical staining and immunofluorescent staining demonstrated that RANTES secreted by apical and narrow cells of mouse epididymal ducts was associated with luminal spermatozoa. Flow cytometric analysis and immunofluorescent labelling revealed that the association between RANTES and spermatozoa of different regions weakened gradually as the spermatozoa moved along the epididymis. Moreover, CCR1, CCR3 and CCR5 were expressed in epididymal spermatozoa and located on the head of epididymal spermatozoa, while RANTES was generally located at the midpiece. In conclusion, RANTES and its receptors were not in the same sperm location, suggesting that RANTES binding to mouse epididymal spermatozoa is independent of CCR1, CCR3 and CCR5.

Gestational diabetes mellitus and impaired glucose tolerance pregnant women.

OBJECTIVE: To evaluate correlations between insulin secretion and resistance in patients with gestational diabetes mellitus (GDM) and gestational impaired glucose tolerance (GIGT). METHODS: Three hundred thirty six pregnant women with an oral glucose tolerance test (OGTT) were tested and measured insulin function indices (IFI), insulin resistance indices (HOMA-IR) as well as blood serum triglycerides (TG), total cholesterol (TCH) and low density lipoprotein cholesterol (LDL-C) concentrations. GIGT patients were further divided into subgroups according to hyperglycemia appearance 1, 2 or 3 hours after glucose ingestion. RESULTS: GDM and GIGT correlated with age (p<0.05), family history of diabetes (p<0.05) and pre-pregnancy body mass indices (BMIs) (p<0.05). Blood pressures were higher in GDM than in GIGT and normal glucose tolerance (NGT) patients (p<0.05). The IFIs were gradually reduced (p<0.05), whereas HOMA-IR was gradually enhanced (p<0.05) in the GIGT and GDM patients. Blood serum TG, TCH and LDL-C concentrations were higher in the GIGT and GDM groups (p<0.05) and the GIGT 1 hour hyperglycemia subgroup had highest pregnancy weight gain and HOMA-IR values (p<0.05). Conclusions : Advanced age, family history of diabetes, high BMIs and blood pressure were risk factors for GIGT and GDM, which were both caused by reduced insulin secretion and enhanced insulin resistance.

Comparative Analysis of Aspergillus oryzae with Normal and Abnormal Color Conidia.

This study focuses on the characteristic of strains with anomalous color conidium and compares with normal color conidium. Comparative analysis of enzymes activity and extracellular proteins revealed that A. oryzae with anomalous color conidium was not different from the strain with normal color conidium. In addition, A. oryzae with anomalous color conidium could not influence the palatability and quality of the soy sauce. These findings provide an insight into A. oryzae with anomalous color conidium.

[The function of ERα in male reproductive system].

Estrogen receptors (ERs), including two sub-types ERα and ERß, belong to the steroid hormone superfamily of nuclear receptors. ERα distributes in the male reproductive system and plays a crucial role in the regulation of male reproduction through estrogen-dependent and -independent ways. In this article, we mainly reviewed the molecular structure, mode of action and location of ERα in the male reproductive system, and explored the mechanism of ERα in regulating the male reproductive system by analyzing different animal models of disrupted ERα.

Predictive value of preoperative platelet count and D-dimer levels for spinal cord injury following acute type a aortic dissection.

BACKGROUND: This study aims to identify the risk factors contributing to spinal cord injury (SCI) following a type A acute aortic dissection (TA-AAD). METHODS: This retrospective study was conducted at a single center and involved 481 patients who received frozen elephant trunk stent implantation for TA-AAD. Additionally, these patients underwent total arch replacement with deep hypothermic circulatory arrest. This study was performed at Fuwai Hospital between September 2016 and April 2020. RESULTS: The resulting data of the multivariate logistic regression analysis demonstrated that preoperative platelet count (odds ratio [OR] = 0.774) and D-dimer levels (OR = 2.247) could serve as independent predictors for postoperative SCI in patients with TA-AAD. CONCLUSION: The findings indicate that preoperative platelet count and D-dimer levels are independent risk factors for postoperative SCI in patients with TA-AAD. This study holds significant clinical implications regarding the prognosis and therapeutic responses for patients with TA-AAD.

Posterior False Lumen and Paraplegia After FET Procedure in Acute Type A Aortic Dissection.

BACKGROUND: Postoperative paraplegia is the major concern with the frozen elephant trunk (FET) procedure in patients with acute type A aortic dissection (ATAAD). It is crucial to identify patients with a high risk of paraplegia before implementing the FET procedure. METHODS: From January 2013 to December 2018, 544 patients with ATAAD who underwent FET procedures were included in this study. The segment number of posterior false lumens (PFLs) between T9 and L2 levels was calculated. In-hospital outcomes and long-term survival were investigated on the basis of the number of PFLs. RESULTS: The average age was 46.5 ± 9.9 years, and the proportion of female patients was 19.5% in this cohort. The incidence of postoperative paraplegia was significantly increased when PFL was present in 3 or more segments. Patients were divided into a high-PFL group (3-6 segments; n = 124) and a low-PFL group (0-2 segments; n = 420). The demographic characteristics were similar between the 2 groups. Involvement of the celiac trunk and the superior mesenteric artery was significantly lower in the high-PFL group (all P < .05). The other baseline characteristics and procedural information were statistically balanced. The incidence of postoperative paraplegia was significantly higher in the high-PHL group (7.3% vs 1.9;P = .006). Multivariable logistic analysis revealed that high PFL was independently associated with postoperative paraplegia after an FET procedure (odds ratio, 3.812; 95% CI, 1.378-10.550; P = .010). Additionally, the moderate nasopharyngeal temperature of hypothermic circulatory arrest (≧23.0 °C) was clarified as a protective factor for paraplegia (odds ratio, 0.112; 95% CI, 0.023-0.535; P = .006). CONCLUSIONS: Patients with ATAAD who present with high PFL between T9 and L2 levels have a significantly high risk of postoperative paraplegia if they undergo an FET procedure.

BDE-47 induces metabolic dysfunction-associated steatotic liver disease (MASLD) through CD36-mediated increased fatty acid uptake and PPARα-induced abnormal fatty acid oxidation in BALB/c mice.

The widespread existence of 2,2',4,4'-tetra-bromodiphenyl ether (BDE-47) in the environment has aroused great concern. BDE-47 induces the occurrence of metabolic dysfunction-associated steatotic liver disease (MASLD), but the mechanism has not been fully elucidated. Here, we further investigate the underlying mechanism using BALB/c mice. After BDE-47 exposure, the livers of mice enlarged, the serum levels of ALT, ALP, TG and TC enhanced, and hepatic steatosis occurred. Transcriptome sequencing identifies 2250 differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis reveals that down-regulated DEGs are mainly enriched in pathways associated with lipid metabolism, particularly in fatty acid (FA) degradation. And up-regulated DEGs are mainly enriched in pathways related to lipid and FA transport. The expression levels of AhR, Pparγ and Cd36 involved in FA uptake are up-regulated, and those of PPARα and target genes including Cpt1 and Cyp4a1 related to ß and ω-oxidation are inhibited. These results reveal BDE-47 could lead to metabolic dysfunction-associated steatotic liver disease (MASLD) by promoting FA uptake via upregulating Cd36 and hindering oxidative utilization by downregulating PPARα.

Risk factors and early outcomes of prolonged mechanical ventilation following redo aortic arch surgery: A retrospective study.

BACKGROUND: Redo aortic arch surgery is complex and associated with higher risks and mortality. Prolonged mechanical ventilation (PMV) after cardiac surgery is linked to early adverse outcomes and increased costs. OBJECTIVES: Identify specific risk factors and early complications associated with PMV following redo aortic arch surgery. METHODS: Retrospective study at Fuwai Hospital involving 203 patients. Data on patient characteristics, intraoperative factors, and outcomes were analyzed. RESULTS: A total of 203 patients were included, with 42.4 % requiring PMV. PMV patients had longer ICU stays (P < 0.001), lower discharge ADL scores (P < 0.001), and higher hospitalization costs (P < 0.001). While there was no significant difference in-hospital mortality between the two groups, the long-term survival rate in the PMV group was lower than that in the non-PMV group (P = 0.029). Multivariate analysis identified longer cardiopulmonary bypass time (OR 1.008, 95% CI, 1.002 - 1.014, P = 0.006), elevated intraoperative red blood cell transfusion(OR 1.214, 95% CI, 1.057 - 1.393, P = 0.006), higher PEEP (OR 1.296, 95% CI 1.089 - 1.542, P = 0.003), and total arch replacement (OR 3.241, 95% CI 1.392 - 7.543, P = 0.006) as independent risk factors for PMV. CONCLUSION: PMV following redo aortic arch surgery is linked to early adverse outcomes, increased healthcare costs, and reduced long-term survival, with longer cardiopulmonary bypass times, elevated intraoperative red blood cell transfusion, higher PEEP, and total arch replacement as independent risk factors.

Metastasis-associated protein 1 participates in regulating luminal acidification of the epididymis via repressing estrogen receptor alpha transcription.

BACKGROUND: As a component of the nucleosome remodeling and deacetylating (NuRD) complex, metastasis-associated protein 1 (MTA1) has been reported to be abundant in male reproductive system and might participate in spermatogenesis and sperm maturation, whereas the precise functional role of MTA1 in these processes is still undetermined. OBJECTIVE: To investigate the effect and potential function of MTA1 in male fertility. MATERIALS AND METHODS: Mta1 knockout mice (Mta1-/- ) were employed to detect their reproductive phenotype. The pH value of Mta1-/- epididymal luminal fluid was measured, and the potential mechanism of MTA1 involved in regulating luminal acidification was detected in vivo and in vitro. A vasectomy model with abnormal pH of epididymal lumen was established to further detect the effect of MTA1 on epididymal luminal microenvironment. RESULTS: Mta1-/- mice were fertile without any detectable defects in spermatogenesis or sperm motility while the deficiency of MTA1 could acidify the initial segment of epididymis to a certain extent. MTA1 could interact with estrogen receptor alpha (ERα) and inhibit the transcription of ERα target gene, hydrogen exchanger 3 (NHE3), and ultimately affect the epididymal luminal milieu. After vasectomy, the Mta1-/- mice presented a more acidic epididymal lumen which was closer to the normal state compared to the wild-type model. DISCUSSION AND CONCLUSION: MTA1 is dispensable for male fertility in mice, but plays a potentially important function in regulating luminal acidification of the epididymis.

Major adverse outcomes in patients with acute type A aortic dissection undergoing total arch replacement with frozen elephant trunk procedure.

BACKGROUND: The objective of this investigation was to identify the risk factors linked to major adverse outcomes (MAO) subsequent to total arch replacement with frozen elephant trunk procedure (TAR+FET) surgery among patients diagnosed with acute type A aortic dissection (ATAAD). Additionally, the study aimed to elucidate the influence of these adverse outcomes on the long-term prognosis of the patients. METHOD: 670 ATAAD patients received the TAR+FET procedure. Multivariable logistic regression was used to investigate the risk factors associated with in-hospital MAO. Additionally, long-term survival outcomes were assessed through follow-up observations of all patients. RESULTS: The overall in-hospital mortality was 4.33%. Among 670 patients, 169 patients (25.22%) developed postoperative MAO. Multivariate analysis showed that in-hospital MAO was positively associated with age (OR = 1.025, 95%CI: 1.005-1.045, P = 0.014), lower limb symptoms (OR = 2.562, 95%CI: 1.407-4.666, P = 0.002), involvement of coronary artery (OR = 2.027, 95%CI: 1.312-3.130, P = 0.001), involvement of left renal artery (OR = 1.998, 95%CI: 1.359-2.938, P < 0.001), CPB time (OR = 1.011, 95%CI: 1.007-1.015, P < 0.001) and WBC counts (OR = 1.045, 95%CI: 1.007-1.083, P = 0.019). MAO group showed a worse long-term prognosis than those non-MAO group (P = 0.002). CONCLUSIONS: While TAR+FET can be an effective treatment option for ATAAD patients, careful patient selection and management are essential in minimizing the risk of MAO and ensuring long-term success.

Unveiling the inverse antimicrobial impact of a hetero-chitooligosaccharide on Candida tropicalis growth and biofilm formation.

Chitosan and chitooligosaccharide (COS) are renowned for their potent antimicrobial prowess, yet the precise antimicrobial efficacy of COS remains elusive due to scant structural information about the utilized saccharides. This study delves into the antimicrobial potential of COS, spotlighting a distinct hetero-chitooligosaccharide dubbed DACOS. In contrast to other COS, DACOS remarkably fosters the growth of Candida tropicalis planktonic cells and fungal biofilms. Employing gradient alcohol precipitation, DACOS was fractionated, unveiling diverse structural characteristics and differential impacts on C. tropicalis. Notably, in a murine model of systemic candidiasis, DACOS, particularly its 70 % alcohol precipitates, manifests a promotive effect on Candida infection. This research unveils a new pathway for exploring the intricate nexus between the structural attributes of chitosan oligosaccharides and their physiological repercussions, underscoring the imperative of crafting chitosan and COS with meticulously defined structural configurations.

Variations in metabolic enzymes cause differential changes of heparan sulfate and hyaluronan in high glucose treated cells on chip.

Glycocalyx dysfunction is believed as the first step in diabetic vascular disease. However, few studies have systematically investigated the influence of HG on the glycocalyx as a whole and its major constituent glycans towards one type of cell. Furthermore, most studies utilized traditional two-dimensional (2D) cultures in vitro, which can't provide the necessary fluid environment for glycocalyx. Here, we utilized vascular glycocalyx on chips to evaluate the changes of glycocalyx and its constituent glycans in HG induced HUVECs. Fluorescence microscopy showed up-regulation of hyaluronan (HA) but down-regulation of heparan sulfate (HS). By analyzing the metabolic enzymes of both glycans, a decrease in the ratio of synthetic/degradative enzymes for HA and an increase in that for HS were demonstrated. Two substrates (UDP-GlcNAc, UDP-GlcA) for the synthesis of both glycans were increased according to omics analysis. Since they were firstly pumped into Golgi apparatus to synthesize HS, less substrates may be left for HA synthesis. Furthermore, the differential changes of HA and HS were confirmed in vessel slides from db/db mice. This study would deepen our understanding of impact of HG on glycocalyx formation and diabetic vascular disease.

Effectiveness of VA-ECMO plus intra-aortic balloon pump for cardiac shock in patients with type A aortic dissection: a case series.

Limited reports exist on the utilization of venoarterial extracorporeal membrane oxygenation (VA-ECMO) following aortic dissection surgery, possibly due to concerns regarding complications. This case series aimed to evaluate the effectiveness and safety of using VA-ECMO in combination with intra-aortic balloon pump (IABP) for managing postoperative cardiogenic shock in patients with type A aortic dissection (AAD). The study included nine patients with an average age of 57.0 ± 9.5 years. The patients underwent various surgical procedures, including coronary artery bypass grafting (CABG) and aortic root reconstruction. The results showed that the combined use of VA-ECMO and IABP was feasible and effective in managing postoperative cardiogenic shock in AAD patients. However, the in-hospital mortality rate was high, with six out of nine patients succumbing to the condition. Among the patients who received VA-ECMO plus IABP in the operating room, four were successfully weaned from VA-ECMO, and three survived with a mean follow-up of 20 months. The study also highlighted the potential risks of renal complications associated with VA-ECMO and IABP. The findings suggest that the combined therapy of VA-ECMO and IABP may be beneficial for patients who have difficulty weaning from cardiopulmonary bypass (CPB) after AAD surgery.