Cryo-EM Structure and Biochemical Analysis of the Human Chemokine Receptor CCR8.

The C-C motif chemokine receptor 8 (CCR8) is a class A G-protein-coupled receptor that has emerged as a promising therapeutic target in cancer and autoimmune diseases. In the present study, we solved the cryo-electron microscopy (cryo-EM) structure of the human CCR8-Gi complex in the absence of a ligand at 2.58 Å. Structural analysis and comparison revealed that our apo CCR8 structure undergoes some conformational changes and is similar to that in the CCL1-CCR8 complex structure, indicating an active state. In addition, the key residues of CCR8 involved in the recognition of LMD-009, a potent nonpeptide agonist, were investigated by mutating CCR8 and testing the calcium flux induced by LMD-009-CCR8 interaction. Three mutants of CCR8, Y1133.32A, Y1724.64A, and E2867.39A, showed a dramatically decreased ability in mediating calcium mobilization, indicating their key interaction with LMD-009 and key roles in activation. These structural and biochemical analyses enrich molecular insights into the agonism and activation of CCR8 and will facilitate CCR8-targeted therapy.

The Tautomerase Activity of Tumor Exosomal MIF Promotes Pancreatic Cancer Progression by Modulating MDSC Differentiation.

Pancreatic cancer is a deadly disease that is largely resistant to immunotherapy, in part because of the accumulation of immunosuppressive cells in the tumor microenvironment (TME). Much evidence suggests that tumor-derived exosomes (TDE) contribute to the immunosuppressive activity mediated by myeloid-derived suppressor cells (MDSC) within the pancreatic cancer TME. However, the underlying mechanisms remain elusive. Herein, we report that macrophage migration inhibitory factor (MIF) in TDEs has a key role in inducing MDSC formation in pancreatic cancer. We identified MIF in both human and murine pancreatic cancer-derived exosomes. Upon specific shRNA-mediated knockdown of MIF, the ability of pancreatic cancer-derived exosomes to promote MDSC differentiation was abrogated. This phenotype was rescued by reexpression of the wild-type form of MIF rather than a tautomerase-null mutant or a thiol-protein oxidoreductase-null mutant, indicating that both MIF enzyme activity sites play a role in exosome-induced MDSC formation in pancreatic cancer. RNA sequencing data indicated that MIF tautomerase regulated the expression of genes required for MDSC differentiation, recruitment, and activation. We therefore developed a MIF tautomerase inhibitor, IPG1576. The inhibitor effectively inhibited exosome-induced MDSC differentiation in vitro and reduced tumor growth in an orthotopic pancreatic cancer model, which was associated with decreased numbers of MDSCs and increased infiltration of CD8+ T cells in the TME. Collectively, our findings highlight a pivotal role for MIF in exosome-induced MDSC differentiation in pancreatic cancer and underscore the potential of MIF tautomerase inhibitors to reverse the immunosuppressive pancreatic cancer microenvironment, thereby augmenting anticancer immune responses.

Exopolysaccharides produced by Antrodia cinnamomea using microparticle-enhanced cultivation: Optimization, primary structure and antibacterial property.

Microparticle-enhanced cultivation was used to enhance the production of exopolysaccharides (EPSs) from Antrodia cinnamomea. The structure and antibacterial activity of two EPSs produced by A. cinnamomea treated with Al2O3 [EPS-Al (crude) and EPS-Al-p (purified)] and without Al2O3 [EPS-C (crude) and EPS-C-p (purified)] were compared. It was observed that the addition of 4 g/L Al2O3 at 0 h resulted in the highest EPS yield of 1.46 g/L, possible attributed to the enhanced permeability of the cell membrane. The structural analysis revealed that EPS-C-p and EPS-Al-p had different structures. EPS-C-p was hyperbranched and spherical with a Mw of 10.8 kDa, while EPS-Al-p was irregular and linear with a Mw of 12.5 kDa. The proportion of Man in EPS-Al-p decreased, while those of Gal and Glc increased when compared to EPS-C-p. The total molar ratios of 6-Glcp and 4-Glcp in EPS-Al-p are 1.45 times that of EPS-C-p. Moreover, EPSs could alter bacterial cell morphology, causing intracellular substance leakage and growth inhibition, with EPS-Al having a stronger antibacterial activity than EPS-C. In conclusion, A. cinnamomea treated with Al2O3 could produce more EPSs, changing monosaccharide composition and glycosidic linkage profile, which could exert stronger antibacterial activity than that produced by untreated A. cinnamomea.

Discovery of a First-in-Class GPR183 Antagonist for the Potential Treatment of Rheumatoid Arthritis.

GPR183 is required for humoral immune responses, and its polymorphisms have been associated with inflammatory autoimmune diseases. Despite increasing attention to GPR183 as a potential therapeutic target for autoimmune diseases, relatively few antagonists have been reported, and none of them have progressed to the clinical stage. In this study, we discovered a highly potent GPR183 antagonist, compound 32, with good aqueous solubility, excellent selectivity, and pharmacokinetic properties. Meanwhile, compound 32 showed exceptional efficacy for rheumatoid arthritis (RA) disease in a mouse collagen-induced arthritis (CIA) model, with an efficacious dose of 0.1 mg/kg. Functionally, compound 32 significantly reduced the swelling of paws and joints, the gene expression of proinflammatory cytokines, MCP-1, MMPs, and VEGF, inflammatory cell infiltration, cartilage damage, pannus formation, and bone erosion in the joints of CIA mice in a dose-dependent manner. Hence, these findings suggest compound 32 as a valuable molecule for further development.

Discovery of a First-in-Class CD38 Inhibitor for the Treatment of Mitochondrial Myopathy.

CD38 is a crucial NADase in mammalian tissues that degrades NAD+ and thus regulates cellular NAD+ levels. Abnormal CD38 expression is linked to mitochondrial dysfunction under several pathological conditions. We present a novel CD38 inhibitor, compound 1, with high potency for CD38 (IC50 of 11 nM) and minimal activity against other targets. In a Pus1 knockout (Pus1-/-) mouse model of mitochondrial myopathy, compound 1 treatment rescued the decline in running endurance in a dose-dependent manner, associated with an elevated NAD+ level in muscle tissue, increased expression of Nrf2, which is known to promote mitochondrial biogenesis, and reduced lactate production. RNA sequencing data indicated that compound 1 has a great effect on mitochondrial function, metabolic processes, muscle contraction/development, and actin filament organization via regulating the expression of relevant genes. Compound 1 is a promising candidate for its excellent in vivo efficacy, favorable pharmacokinetics, and attractive safety profile.

Discovery of a Potent and Selective CCR8 Small Molecular Antagonist IPG7236 for the Treatment of Cancer.

Recently, there has been increasing evidence indicating that the CC chemokine receptor 8 (CCR8) plays an important role in mediating the recruitment and immunosuppressive function of regulatory T (Treg) cells in the tumor microenvironment. Therefore, the development of a specific CCR8 antagonist presents a potential therapeutic strategy against cancer. Despite a few small molecules having been reported as CCR8 antagonists, none has progressed to the clinical stage. Herein, we described a potent and selective CCR8 antagonist (compound 1, IPG7236) as the first small molecule to advance to the clinical stage. IPG7236 demonstrated an anti-cancer effect via modulating Treg and cytotoxic T (CD8+ T) cells. IPG7236 alone or in combination with PD-1 antibody exhibited significant tumor suppression effects in the mouse xenograft model of human breast cancer. IPG7236 is a promising clinical candidate that targets CCR8 with excellent in vitro ADMET properties, pharmacokinetics, safety profiles, and in vivo efficacy.

Catalytic mechanism of N-containing biochar on volatile-biochar interaction for the same origin pyrolysis.

Nitrogen, as a common element, is widely present in biomass. The effects of nitrogenous substances on the same origin pyrolysis of biomass and the consequences of N-containing biochar on the catalytic process of volatiles are important for further analyzing the pyrolysis mechanism of biomass. In this research, N-containing biochar was prepared under different conditions, and the interaction between N-containing biochar and biomass pyrolysis volatiles at 400-700 °C was studied. The results show that N-containing biochar can simultaneously participate in reactions as adsorbents, catalysts, and reactants. Its catalytic effect is obviously different for various N configurations. Pyridinic N and pyrrolic N can promote the cracking of lignin into methoxy phenol compounds and promote the further cracking of 5-hydroxymethylfurfural. Graphitic N and oxidized N can promote the further decomposition of phenol and the conversion of D-xylose into small-molecule ketones. In addition, oxidized N can also inhibit the cracking of lignin to produce guaiacol. In the long-term interaction, the highly active pyridinic N tends to convert to a more stable graphitic N.

TLR4 Enhances Cerebral Ischemia/Reperfusion Injury via Regulating NLRP3 Inflammasome and Autophagy.

Ischemic stroke is a kind of central nervous disease characterized by high morbidity, high mortality, and high disability. Inflammation and autophagy play important roles in cerebral ischemia/reperfusion (CI/R) injury. The present study characterizes the effects of TLR4 activation on inflammation and autophagy in CI/R injury. An in vivo CI/R rat injury model and an in vitro hypoxia/reoxygenation (H/R) SH-SY5Y cell model were established. Brain infarction size, neurological function, cell apoptosis, inflammatory mediators' levels, and gene expression were measured. Infarction, neurological dysfunction, and neural cell apoptosis were induced in CI/R rats or in H/R-induced cells. The expression levels of NLRP3, TLR4, LC3, TNF-α, interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-18 (IL-18) clearly increased in I/R rats or in H/R-induced cells, while TLR4 knockdown significantly suppressed NLRP3, TLR4, LC3, TNF-α, and interleukin-1/6/18 (IL-1/6/18) in H/R-induced cells, as well as cell apoptosis. These data indicate that TLR4 upregulation induced CI/R injury via stimulating NLRP3 inflammasome and autophagy. Therefore, TLR4, is a potential therapeutic target to improve management of ischemic stroke.

Efficient production of Antrodin C by microparticle-enhanced cultivation of medicinal mushroom Antrodia cinnamomea.

The microparticle-enhanced cultivation (MPEC) was used to enhance the production of Antrodin C by submerged fermentation of medicinal mushroom Antrodia cinnamomea. The crucial factors such as types, sizes, concentrations, and addition time of microparticles were optimized. The mechanism of MPEC on the membrane permeability and fluidity of A. cinnamomea and the expression of key genes in Antrodin C were investigated. When talc (18 µm, 2 g/L) was added into the fermentation liquid at 0 h, the promoting effect on Antrodin C was the best. The maximum yield of Antrodin C was 1615.7 mg/L, which was about 2.98 times of the control (541.7 mg/L). Talc slightly damaged the mycelia of A. cinnamomea, increased the release of intracellular constituents, and enhanced the index of unsaturated fatty acid. In addition, the key genes (IDI, E2.3.3.10, HMGCR, atoB) that might play an important role in the synthesis of the triquine-type sesquiterpene Antrodin C, were upregulated. In conclusion, talc increased the permeability and fluidity of cell membrane, upregulated the key genes and improved the biosynthesis process to enhance the yield of Antrodin C in the submerged fermentation of A. cinnamomea.

The clinical implications and molecular features of intrahepatic cholangiocarcinoma with perineural invasion.

BACKGROUND: Perineural invasion (PNI) is associated with metastasis in malignancies, including intrahepatic cholangiocarcinoma (ICC), and is correlated with poor prognosis. METHODS: The study included three large cohorts: ZS-ICC and TMA cohorts from our team, MSK cohort from a public database, and a small cohort named cohort 4. Prognostic implications of PNI were investigated in MSK cohort and TMA cohort. PNI-related genomic and transcriptomic profiles were analyzed in MSK and ZS-ICC cohorts. GO, KEGG, and ssGSEA analyses were performed. Immunohistochemistry was used to investigate the relationship between PNI and markers of neurons, hydrolases, and immune cells. The efficacy of adjuvant therapy in ICC patients with PNI was also assessed. RESULTS: A total of 30.6% and 20.7% ICC patients had PNI in MSK and TMA cohorts respectively. Patients with PNI presented with malignant phenotypes such as high CA19-9, the large bile duct type, lymph node invasion, and shortened overall survival (OS) and relapse-free survival (RFS). Nerves involved in PNI positively express tyrosine hydroxylase (TH), a marker of sympathetic nerves. Patients with PNI showed high mutation frequency of KRAS and an immune suppressive metastasis prone niche of decreased NK cell, increased neutrophil, and elevated PD-L1, CD80, and CD86 expression. Patients with PNI had an extended OS after adjuvant therapy with TEGIO, GEMOX, or capecitabine. CONCLUSION: Our study deciphered the genomic features and the immune suppressive metastasis-prone niche in ICC with PNI. Patients with PNI showed a poor prognosis after surgery but a good response to adjuvant chemotherapy.

lncRNA PINK1-AS Aggravates Cerebral Ischemia/Reperfusion Oxidative Stress Injury through Regulating ATF2 by Sponging miR-203.

Ischemic stroke is a common disease that led to high mortality and high disability. NADPH oxidase 2- (NOX2-) mediated oxidative stress and long noncoding RNA have important roles in cerebral ischemia/reperfusion (CI/R) injury, whereas whether there is interplay between them remains to be clarified. This study was performed to observe the role of lncRNA PINK1-antisense RNA (PINK1-AS) in NOX2 expression regulation. An in vivo rat model (MCAO) and an in vitro cell model (H/R: hypoxia/reoxygenation) were utilized for CI/R oxidative stress injury investigation. The expression levels of lncRNA PINK1-AS, activating transcription factor 2 (ATF2), NOX2, and caspase-3 and the production level of ROS and cell apoptosis were significantly increased in CI/R injury model rats or in H/R-induced SH-SY5Y cells, but miR-203 was significantly downregulated. There was positive correlation between PINK1-AS expression level and ROS production level. PINK1-AS and ATF2 were found to be putative targets of miR-203. Knockdown of lncRNA PINK1-AS or ATF2 or the overexpression of miR-203 significantly reduced oxidative stress injury via inhibition of NOX2. Overexpression of lncRNA PINK1 significantly led to oxidative stress injury in SH-SY5Y cells through downregulating miR-203 and upregulating ATF2 and NOX2. lncRNA PINK1-AS and ATF2 were the targets of miR-203, and the lncRNA PINK1-AS/miR-203/ATF2/NOX2 axis plays pivotal roles in CI/R injury. Therefore, lncRNA PINK1-AS is a possible target for CR/I injury therapy by sponging miR-203.

The mechanisms and roles of melatonin in gastrointestinal cancer.

Gastrointestinal (GI) cancer is a global health problem with wide lesions and numerous cases. The increased morbidity and mortality of GI cancer is a socio-economic challenge for decades to come. Melatonin, a nature indolamine, exerts a crucial role in molecular interactions involved in multiple functional and physiological processes. Increasing evidence indicates that melatonin can modulate GI tract, decrease the occurrence of GI cancer, and enhance the sensitivity to chemoradiotherapy. However, little is known about the exact role of melatonin in anti-carcinogenesis. In this review, we discuss the action of the beneficial effects of melatonin in GI carcinogenesis. Furthermore, we compile the understanding of the role of melatonin in GI cancer, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), colorectal cancer (CRC), and pancreatic cancer (PC). In addition, the potential therapeutic application and clinical evaluation of melatonin in GI cancer are also discussed.

Del Nido versus HTK cardioplegia for myocardial protection during adult complex valve surgery: a retrospective study.

BACKGROUND: Histidine-tryptophan-ketoglutarate (HTK) and del Nido (DN) cardioplegia are intracellular-type and extracellular-type solution respectively, both can provide a long period of myocardial protection with single-dose infusion, but studies comparing the two are rare for adult cardiac surgery. This study aims to evaluate whether DN is suitable for cardioplegia in complex and high-risk valve surgery with long-term cardiac ischemia when compared with HTK. METHODS: The perioperative records of adult patients infused with DN/HTK as a cardioplegic solution who underwent complex valve surgery with an expected myocardial ischaemic duration longer than 90 min between Oct 2018 and Oct 2019 were analysed retrospectively. RESULTS: Of the 160 patients who received DN/HTK and underwent complex valve surgery, we propensity matched 73 pairs. Both groups achieved satisfactory cardiac arrest effects, and no significant difference was found in their cTnI and CK-MB levels within 12 to 72 h postoperatively. The DN group had a higher rate of return to spontaneous rhythm (0.88 v 0.52, P < 0.001), a lower frequency of postoperative severe arrythmias (12% v 26%, P = 0.036), a higher postoperative stroke volume (65 v 59 ml, P = 0.011) and a higher cardiac output (6.0 v 4.9 L/min, P = 0.007) as evaluated by echocardiography, fewer transfusions and shorter ICU stays (both P < 0.05). The two groups had similar inotrope usage and similar incidences of low cardiac output, morbidities and mortality. Subgroup analysis showed that when the aortic clamping time was greater than 120 min, the advantages of DN were weakened. CONCLUSIONS: DN can be safely applied to complex valve surgery, and it has a similar myocardial protection effect as HTK. Further prospective studies are required to verify these retrospective findings. Trial registration retrospectively registered.

CT-Guided Microcoil Localization of Small Peripheral Pulmonary Nodules to Direct Video-Assisted Thoracoscopic Resection without the Aid of Intraoperative Fluoroscopy

Objective@#To evaluate the feasibility, safety, and effectiveness of CT-guided microcoil localization of solitary pulmonary nodules (SPNs) for guiding video-assisted thoracoscopic surgery (VATS). @*Materials and Methods@#Between June 2016 and October 2019, 454 consecutive patients with 501 SPNs who received CTguided microcoil localization before VATS in our institution were enrolled. The diameter of the nodules was 0.93 ± 0.49 cm, and the shortest distance from the nodules to the pleura was 1.41 ± 0.95 cm. The distal end of the microcoil was placed less than 1 cm away from the nodule, and the proximal end was placed outside the visceral pleura. VATS was performed under the guidance of implanted microcoils without the aid of intraoperative fluoroscopy. @*Results@#All 501 nodules were marked with microcoils. The time required for microcoil localization was 12.8 ± 5.2 minutes. Microcoil localization-related complications occurred in 179 cases (39.4%). None of the complications required treatment. A total of 463 nodules were successfully resected under the guidance of implanted microcoils. VATS revealed 38 patients with dislocated microcoils, of which 28 underwent wedge resection (21 cases under the guidance of the bleeding points of pleural puncture, 7 cases through palpation), 5 underwent direct lobectomy, and the remaining 5 underwent a conversion to thoracotomy. In 4 cases, a portion of the microcoil remained in the lung parenchyma. @*Conclusion@#CT-guided microcoil localization of SPNs is safe and reliable. Marking the nodule and pleura simultaneously with microcoils can effectively guide the resection of SPNs using VATS without the aid of intraoperative fluoroscopy.

Critical quality attribute assessment of big brand traditional Chinese medicine: study on NIR field detection method of chemical properties of moisture in Tongren Niuhuang Qingxin Pills / 中国中药杂志

For the field detection problems of critical quality attribute(CQA) of moisture content in traditional Chinese medicine(TCM) manufacturing process, big brand TCM Tongren Niuhuang Qingxin Pills were used as the carrier, to establish a moisture content NIR field detection model with or without cellophane in real world production with use of near infrared(NIR) spectroscopy combined with stoichiometry. With the moisture content determined by drying method as reference value, the partial least square method(PLS) was used to analyze the correlation between the spectrum and the moisture reference value. Then the spectral pretreatment methods were screened and optimized to further improve the accuracy and stability of the model. The results showed that the best quantitative model was developed by the spectral data pretreatment of standard normal variate(SNV) with the latent variable factor number of 2 and 7 of Tongren Niuhuang Qingxin Pills with or without cellophane samples. The prediction coefficient of determination(R_(pre)~2) and standard deviation of prediction(RMSEP) of the model with cellophane samples were 0.765 7 and 0.157 2%; R_(pre)~2 and RMSEP of the model without cellophane samples were 0.772 2 and 0.207 8%. The NIR quantitative models of moisture content of Tongren Niuhuang Qingxin Pills with and without cellophane both showed good predictive performance to realize the rapid, accurate and non-destructive quantitative analysis of moisture content in such pills, and provide a method for the field quality control of the critical chemical attributes of moisture in the manufacturing of big brand TCM.

CT-Guided Microcoil Localization of Small Peripheral Pulmonary Nodules to Direct Video-Assisted Thoracoscopic Resection without the Aid of Intraoperative Fluoroscopy

Objective@#To evaluate the feasibility, safety, and effectiveness of CT-guided microcoil localization of solitary pulmonary nodules (SPNs) for guiding video-assisted thoracoscopic surgery (VATS). @*Materials and Methods@#Between June 2016 and October 2019, 454 consecutive patients with 501 SPNs who received CTguided microcoil localization before VATS in our institution were enrolled. The diameter of the nodules was 0.93 ± 0.49 cm, and the shortest distance from the nodules to the pleura was 1.41 ± 0.95 cm. The distal end of the microcoil was placed less than 1 cm away from the nodule, and the proximal end was placed outside the visceral pleura. VATS was performed under the guidance of implanted microcoils without the aid of intraoperative fluoroscopy. @*Results@#All 501 nodules were marked with microcoils. The time required for microcoil localization was 12.8 ± 5.2 minutes. Microcoil localization-related complications occurred in 179 cases (39.4%). None of the complications required treatment. A total of 463 nodules were successfully resected under the guidance of implanted microcoils. VATS revealed 38 patients with dislocated microcoils, of which 28 underwent wedge resection (21 cases under the guidance of the bleeding points of pleural puncture, 7 cases through palpation), 5 underwent direct lobectomy, and the remaining 5 underwent a conversion to thoracotomy. In 4 cases, a portion of the microcoil remained in the lung parenchyma. @*Conclusion@#CT-guided microcoil localization of SPNs is safe and reliable. Marking the nodule and pleura simultaneously with microcoils can effectively guide the resection of SPNs using VATS without the aid of intraoperative fluoroscopy.

Diagnostic value of artificial intelligence-assisted diagnostic system for pulmonary cancer based on CT images: A systematic review and meta-analysis of 4 771 patients / 中国胸心血管外科临床杂志

@#Objective    To evaluate the diagnostic value of artificial intelligence (AI)-assisted diagnostic system for pulmonary cancer based on CT images. Methods    Databases including PubMed, The Cochrane Library, EMbase, CNKI, WanFang Data and Chinese BioMedical Literature Database (CBM) were electronically searched to collect relevant studies on AI-assisted diagnostic system in the diagnosis of pulmonary cancer from 2010 to 2019. The eligible studies were selected according to inclusion and exclusion criteria, and the quality of included studies was assessed and the special information was identified. Then, meta-analysis was performed using RevMan 5.3, Stata 12.0 and SAS 9.4 softwares. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were pooled and the summary receiver operating characteristic (SROC) curve was drawn. Meta-regression analysis was used to explore the sources of heterogeneity. Results    Totally 18 studies were included with 4 771 patients. Random effect model was used for the analysis due to the heterogeneity among studies. The results of meta-analysis showed that the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnosis odds ratio and area under the SROC curve were   0.87 [95%CI (0.84, 0.90)], 0.89 [95%CI (0.84, 0.92)], 7.70 [95%CI (5.32, 11.15)], 0.14 [95%CI (0.11, 0.19)], 53.54 [95%CI (30.68, 93.42)] and 0.94 [95%CI (0.91, 0.95)], respectively. Conclusion    AI-assisted diagnostic system based on CT images has high diagnostic value for pulmonary cancer, and thus it is worthy of clinical application. However, due to the limited quality and quantity of included studies, above results should be validated by more studies.

Preoperative autologous platelet pheresis reduces allogeneic platelet use and improves the postoperative PaO2/FiO2 ratio in complex aortic surgery: a retrospective analysis.

OBJECTIVES: An autologous platelet-rich plasma pheresis (aPP) strategy can harvest partial whole blood that is separated into erythrocytes, plasma and platelets, and can reduce blood loss and transfusion during cardiovascular surgery using cardiopulmonary bypass (CPB). However, the blood and organ conservation effects of this technique have not been confirmed in the context of complex aortic surgery. METHODS: Perioperative records of 147 adult patients who underwent complex aortic surgery were analysed retrospectively. RESULTS: All patients received regular blood conservation treatment, and 57 patients received aPP. Whether or not the participants were propensity matched, decreased platelet and cryoprecipitate transfusions were found in the aPP group (both P < 0.001), but there were non-significant differences in erythrocyte transfusion, Sequential Organ Failure Assessment scores and other outcomes when compared with the same parameters in the non-aPP group. The aPP group had a higher arterial oxygen partial pressure to inhaled oxygen concentration ratio on postoperative days 1, 2 and 7 than the non-aPP group (P < 0.001, P < 0.001 and P = 0.048, respectively). CONCLUSIONS: The utilization of aPP was associated with a reduction in allogeneic platelet and cryoprecipitate transfusions as well as minor lung-protective effects during complex aortic surgery using CPB.