Single-cell transcriptomics reveal the microenvironment landscape of perfluorooctane sulfonate-induced liver injury in female mice.

Epidemic and animal studies have reported that perfluoroalkyl and polyfluoroalkyl substances (PFASs) are strongly associated with liver injury; however, to date, the effects of PFASs on the hepatic microenvironment remain largely unknown. In this study, we established perfluorooctane sulfonic acid (PFOS)-induced liver injury models by providing male and female C57BL/6 mice with water containing PFOS at varying doses for 4 weeks. Hematoxylin and eosin staining revealed that PFOS induced liver injury in both sexes. Elevated levels of serum aminotransferases including those of alanine aminotransferase and aspartate transaminase were detected in the serum of mice treated with PFOS. Female mice exhibited more severe liver injury than male mice. We collected the livers from female mice and performed single-cell RNA sequencing. In total, 36,529 cells were included and grouped into 10 major cell types: B cells, granulocytes, T cells, NK cells, monocytes, dendritic cells, macrophages, endothelial cells, fibroblasts, and hepatocytes. Osteoclast differentiation was upregulated and the T cell receptor signaling pathway was significantly downregulated in PFOS-treated livers. Further analyses revealed that among immune cell clusters in PFOS-treated livers, Tcf7+CD4+T cells were predominantly downregulated, whereas conventional dendritic cells and macrophages were upregulated. Among the fibroblast subpopulations, hepatic stellate cells were significantly enriched in PFOS-treated female mice. CellphoneDB analysis suggested that fibroblasts interact closely with endothelial cells. The major ligand-receptor pairs between fibroblasts and endothelial cells in PFOS-treated livers were Dpp4_Cxcl12, Ackr3_Cxcl12, and Flt1_complex_Vegfa. These genes are associated with directing cell migration and angiogenesis. Our study provides a general framework for understanding the microenvironment in the livers of female mice exposed to PFOS at the single-cell level.

Animal-derived food allergen: A review on the available crystal structure and new insights into structural epitope.

Immunoglobulin E (IgE)-mediated food allergy is a rapidly growing public health problem. The interaction between allergens and IgE is at the core of the allergic response. One of the best ways to understand this interaction is through structural characterization. This review focuses on animal-derived food allergens, overviews allergen structures determined by X-ray crystallography, presents an update on IgE conformational epitopes, and explores the structural features of these epitopes. The structural determinants of allergenicity and cross-reactivity are also discussed. Animal-derived food allergens are classified into limited protein families according to structural features, with the calcium-binding protein and actin-binding protein families dominating. Progress in epitope characterization has provided useful information on the structural properties of the IgE recognition region. The data reveals that epitopes are located in relatively protruding areas with negative surface electrostatic potential. Ligand binding and disulfide bonds are two intrinsic characteristics that influence protein structure and impact allergenicity. Shared structures, local motifs, and shared epitopes are factors that lead to cross-reactivity. The structural properties of epitope regions and structural determinants of allergenicity and cross-reactivity may provide directions for the prevention, diagnosis, and treatment of food allergies. Experimentally determined structure, especially that of antigen-antibody complexes, remains limited, and the identification of epitopes continues to be a bottleneck in the study of animal-derived food allergens. A combination of traditional immunological techniques and emerging bioinformatics technology will revolutionize how protein interactions are characterized.

Comparative analysis of tropomyosin allergenicity in three different species of molluscs: insights into the role of amino acid composition in IgE epitopes.

Limited research has been conducted on the differences in allergenicity among Alectryonella plicatula tropomyosin (ATM), Haliotis discus hannai tropomyosin (HTM), and Mimachlamys nobilis tropomyosin (MTM) in molluscs. Our study aimed to comprehensively analyze and compare their immunoreactivity, sensitization, and allergenicity while simultaneously elucidating the underlying molecular mechanisms involved. We assessed the immune binding activity of TM utilizing 86 sera from allergic patients and evaluated sensitization and allergenicity through two different types of mouse models. The dot-blot and basophil activation test assays revealed strong immunoreactivity for HTM, ATM, and MTM, with HTM exhibiting significantly lower levels compared to ATM. In the BALB/c mouse sensitization model, all TM groups stimulated the production of specific antibodies, elicited IgE-mediated immediate hypersensitivity responses, and caused an imbalance in the IL-4/IFN-γ ratio. Similarly, in the BALB/c mouse model of food allergy, all TM variants induced IgE-mediated type I hypersensitivity responses, leading to the development of food allergies characterized by clinical symptoms and an imbalance in the IL-4/IFN-γ ratio. The stimulation ability of sensitization and the severity of food allergies consistently ranked as ATM > MTM > HTM. Through an in-depth analysis of non-polar amino acid frequency and polar hydrogen bonds, HTM exhibited higher frequencies of non-polar amino acids in its amino acid sequence and IgE epitopes, in comparison with ATM and MTM. Furthermore, HTM demonstrated a lower number of polar hydrogen bonds in IgE epitopes. Overall, HTM exhibited the lowest allergenic potential in both allergic patients and mouse models, likely due to its lower polarity in the amino acid sequence and IgE epitopes.

Immunoglobulin E Epitope Mapping and Structure-Allergenicity Relationship Analysis of Crab Allergen Scy p 9.

Filamin C is an allergen of Scylla paramamosain (Scy p 9), and six IgE linear epitopes of the allergenic predominant region had previously been validated. However, the IgE epitope and structure-allergenicity relationship of Scy p 9 are unclear. In this study, a hydrophobic bond was found to be an important factor of conformation maintaining. The critical amino acids in the six predicted conformational epitopes were mutated, and the IgE-binding capacity and surface hydrophobicity of four mutants (E216A, T270A, Y699A, and V704A) were reduced compared to Scy p 9. Ten linear epitopes were verified with synthetic peptides, among which L-AA187-205 had the strongest IgE-binding capacity. In addition, IgE epitopes were mapped in the protruding surface of the tertiary structure, which were conducive to binding with IgE and exhibited high conservation among filamin genes. Overall, these data provided a basis for IgE epitope mapping and structure-allergenicity relationship of Scy p 9.

Effects of carrimycin on biomarkers of inflammation and immune function in tumor patients with sepsis: A multicenter double-blind randomized controlled trial.

Carrimycin is a potential immune-regulating agent for sepsis in patients with tumors. In this study, we investigated its effects on inflammation and immune function in tumor patients with sepsis. In total, 120 participants were randomized to receive either carrimycin treatment (400 mg/day) (n = 62) or placebo (n = 58) for 7 days. The primary outcomes were immune-related indicators. Subsequently, patients were stratified into two subgroups (CD4 < 38.25% and CD8 < 25.195%). Ninety-nine participants were analyzed: 47 and 52 in the carrimycin and placebo groups, respectively. HLA-DR levels were rapidly increased in the carrimycin group; however, the placebo group initially experienced a decline in HLA-DR level at 1 day after administration. In the subgroup with CD4 < 38.25%, the carrimycin group exhibited significantly higher HLA-DR levels than the placebo group (2.270, P = 0.023) 1 day after administration and the degree of increase in HLA-DR in the carrimycin group was higher than that in the placebo group (2.057, P = 0.040). In the CD8 < 25.195% subgroup, the carrimycin group demonstrated significantly higher levels of CD8+ T cells than the placebo group at 3 (2.300,P = 0.027) and 5 (2.106, P = 0.035) days after administration. Carrimycin intervention led to significant reductions in the SOFA, APACHE II, PCT, and CRP levels. No adverse events were observed. In tumor patients with sepsis, particularly in those experiencing immunological suppression, carrimycin effectively regulates immune responses by increasing HLA-DR and CD8+ T cell levels and plays an anti-infective role, reducing disease severity. (Chictr.org.cn, ID Number: ChiCTR2000032339).

IgE Epitope Analysis and Hypo-Immunoreactivity Derivative of Arginine Kinase in Mantis Shrimp (Oratosquilla oratoria).

As the main allergenic food, shrimp can trigger allergic reactions in various degrees. In this study, arginine kinase (AK) was identified as an allergen in Oratosquilla oratoria by LC-MS/MS. The open reading frame of AK was obtained, which included 356 amino acids, and recombinant AK (rAK) was expressed in Escherichia coli. The results of immunological analysis and circular dichroism showed that rAK displayed similar IgG-/IgE-binding activity and structure as native AK. Besides, five IgE linear epitopes of AK were verified by serological analysis, on the basis of which an epitope-deleted derivative was obtained and named as mAK-L. It has been shown that mAK-L displayed hypo-immunoreactivity compared to rAK, and the contents of secondary structures were different. In conclusion, these discoveries enrich the overall understanding of crustacean allergens and epitopes and set the foundations for food allergy diagnosis and immunotherapy.

Effects of three processing technologies on the structure and immunoreactivity of α-tropomyosin from Haliotis discus hannai.

The subunit of tropomyosin (α-TM) from Haliotis discus hannai is an important allergen. The methods to reduce the immunoreactivity of α-TM are worth investigating. Thus, this study confirmed the reacted conditions of α-TM with transglutaminase (TG)-catalyzed cross-linking reaction, TG-catalyzed glycosylation, and glycation. Three processing technologies reduced significantly the contents of α-helix and hydrophobic force of α-TM and increased the surface hydrophobicity. A serological experiment confirmed that the glycated α-TM with xylose showed the lowest IgG/IgE-binding capacity. The inhabitation dot blot displayed that five epitope peptides could bind with the site-specific IgE prepared by the glycated α-TM. Three in nine glycated sites (M68, N202, and N203) were verified to modify-two epitopes (L-HTM-3 and L-HTM-7) of α-TM, which affected the immunoreactivity of α-TM during glycation. These results indicated that glycation would be desired for developing hypo-allergenic abalone products.

The Effects of Temperature Management on Brain Microcirculation, Oxygenation and Metabolism.

PURPOSE: Target temperature management (TTM) is often used in patients after cardiac arrest, but the effects of cooling on cerebral microcirculation, oxygenation and metabolism are poorly understood. We studied the time course of these variables in a healthy swine model. METHODS: Fifteen invasively monitored, mechanically ventilated pigs were allocated to sham procedure (normothermia, NT; n = 5), cooling (hypothermia, HT, n = 5) or cooling with controlled oxygenation (HT-Oxy, n = 5). Cooling was induced by cold intravenous saline infusion, ice packs and nasal cooling to achieve a body temperature of 33-35 °C. After 6 h, animals were rewarmed to baseline temperature (within 5 h). The cerebral microvascular network was evaluated (at baseline and 2, 7 and 12 h thereafter) using sidestream dark-field (SDF) video-microscopy. Cerebral blood flow (laser Doppler MNP100XP, Oxyflow, Oxford Optronix, Oxford, UK), oxygenation (PbtO2, Licox catheter, Integra Lifesciences, USA) and lactate/pyruvate ratio (LPR) using brain microdialysis (CMA, Stockholm, Sweden) were measured hourly. RESULTS: In HT animals, cerebral functional capillary density (FCD) and proportion of small-perfused vessels (PSPV) significantly decreased over time during the cooling phase; concomitantly, PbtO2 increased and LPR decreased. After rewarming, all microcirculatory variables returned to normal values, except LPR, which increased during the rewarming phase in the two groups subjected to HT when compared to the group maintained at normothermia. CONCLUSIONS: In healthy animals, TTM can be associated with alterations in cerebral microcirculation during cooling and altered metabolism at rewarming.

Identification of linear epitopes and their major role in the immunoglobulin E-binding capacity of tropomyosin from Alectryonella plicatula.

Tropomyosin (TM) is an important allergen in molluscans. However, there was a lack of information about TM as an allergen in oysters. TM was purified and identified from Alectryonella plicatula (ATM), and its primary sequence was cloned and encoded with 284 amino acids (AAs). Chemical denaturants were used to destroy the structure to confirm that linear epitopes played a major role in the immunoglobulin E-binding capacity of ATM. Subsequently, nine linear epitopes were identified using a serological test. The peptide with AA27-41 was regarded as the key epitope because it could be recognized strongly by most sera of oyster-sensitive individuals in comparison to other epitope peptides. Finally, the epitopes and the primary sequence of TM among shellfish were aligned to find the two conserved epitopes (AA117-132 and AA164-178) in oyster, octopus, abalone, scallop, clam, shrimp, and crab. Overall, these data provide a foundation for the allergenicity and cross-reactivity of TM.

Penpulimab, an Fc-Engineered IgG1 Anti-PD-1 Antibody, With Improved Efficacy and Low Incidence of Immune-Related Adverse Events.

Background: IgG4 anbibodies are deficient in stability and may contribute to tumor-associated escape from immune surveillance. We developed an IgG1 backbone anti-programmed cell death protein-1 (PD-1) antibody, penpulimab, which is designed to remove crystallizable fragment (Fc) gamma receptor (FcγR) binding that mediates antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and proinflammatory cytokine release. Methods: Aggregation of different anti-PD-1 antibodies was tested by size exclusion chromatography, and melting temperature midpoint (Tm) and aggregation temperature onset (Tagg) were also determined. The affinity constants of penpulimab for PD-1 and human FcγRs were measured by surface plasmon resonance and biolayer interferometry. ADCC and ADCP were determined in cellular assays and antibody-dependent cytokine release (ADCR) from human macrophages was detected by ELISA. Binding kinetics of penpulimab to human PD-1 was determined by Biacore, and epitope/paratope mapping of PD-1/penpulimab was investigated using x-ray crystallography. Additionally, patients from six ongoing trials were included for analysis of immune-related adverse events (irAEs). Results: Penpulimab demonstrated better stability and a lower level of host-cell protein residue compared with IgG4 backbone anti-PD-1 antibodies. As expected, penpulimab exhibited no apparent binding to FcγRIa, FcγRIIa_H131, FcγRIIIa_V158 and FcγRIIIa_F158, elicited no apparent ADCC and ADCP activities, and induced no remarkable IL-6 and IL-8 release by activated macrophages in vitro. Penpulimab was shown in the co-crystal study to bind to human PD-1 N-glycosylation site at N58 and had a slower off-rate from PD-1 versus nivolumab or pembrolizumab. Four hundred sixty-five patients were analyzed for irAEs. Fifteen (3.2%) patients had grade 3 or above irAEs. No death from irAEs was reported. Conclusions: IgG1 backbone anti-PD1 antibody penpulimab has a good stability and reduced host cell protein residue, as well as potent binding to the antigen. Fc engineering has eliminated Fc-mediated effector functions of penpulimab including ADCC, ADCP and reduced ADCR, which may contribute to its more favorable safety profile. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: AK105-101: NCT03352531, AK105-201: NCT03722147, AK105-301: NCT03866980, AK105-202:NCT03866967, AK105-203: NCT04172571, AK105-204: NCT04172506.

Diagnostic Value of Coronary Computed Tomography Angiography Image under Automatic Segmentation Algorithm for Restenosis after Coronary Stenting.

The diagnostic efficacy of coronary computed tomography angiography (CTA) images of coronary arteries in restenosis after coronary stenting based on the combination of the convolutional neural network (CNN) algorithm and the automatic segmentation algorithm for region growth of vascular similarity features was explored to provide a more effective diagnostic method for patients. 130 patients with coronary artery disease were randomly selected as the research objects, and they were averagely classified into the control group (conventional coronary CTA image diagnosis) and the observation group (coronary CTA image diagnosis based on an improved automatic segmentation algorithm). Based on the diagnostic criteria of coronary angiography (CAG), the efficacy of two kinds of coronary CTA images on the postoperative subsequent visit of coronary heart disease (CHD) stenting was evaluated. The results showed that the accuracy of the CNN algorithm was 87.89%, and the average voxel error of the improved algorithm was signally lower than that of the traditional algorithm (1.8921 HU/voxel vs. 7.10091 HU/voxel) (p < 0.05). The average score of the coronary CTA image in the observation group was higher than that in the control group (2.89 ± 0.11 points vs. 2.01 ± 0.73 points) (p < 0.05). The diagnostic sensitivity (91.43%), specificity (86.76%), positive predictive value (88.89%), negative predictive value (89.66%), and accuracy (89.23%) of the observation group were higher than those of the control group (p < 0.05). In conclusion, the region growth algorithm under the CNN algorithm and vascular similarity features had an accurate segmentation effect, which was helpful for the diagnosis of CTA image in restenosis after coronary stenting.

Effects of Reversal of Hypotension on Cerebral Microcirculation and Metabolism in Experimental Sepsis.

The effects of reversal of hypotension on the cerebral microcirculation, oxygenation, and metabolism in septic shock remain unclear. In 12 sheep, peritonitis was induced by injection of feces into the abdominal cavity. At the onset of septic shock (mean arterial pressure (MAP) < 65 mmHg, unresponsive to fluid challenge), a norepinephrine infusion was titrated in eight sheep to restore a MAP ≥ 75 mmHg; the other four sheep were kept hypotensive. The microcirculation of the cerebral cortex was evaluated using side-stream dark-field video-microscopy. Brain partial pressure of oxygen (PbtO2) was measured, and cerebral metabolism was assessed using microdialysis. All animals developed septic shock after a median of 15 (14−19) h. When MAP was raised using norepinephrine, the PbtO2 increased significantly (from 41 ± 4 to 55 ± 5 mmHg), and the cerebral lactate/pyruvate ratio decreased (from 47 ± 13 to 28 ± 4) compared with values at shock onset. Changes in the microcirculation were unchanged with restoration of MAP and the glutamate increased further (from 17 ± 11 to 23 ± 16 µM), as it did in the untreated animals. In septic shock, the correction of hypotension with vasopressors may improve cerebral oxygenation but does not reverse the alterations in brain microcirculation or cerebral metabolism.

Crystal Structure Analysis and IgE Epitope Mapping of Allergic Predominant Region in Scylla paramamosain Filamin C, Scy p 9.

Filamin C (FLN c) is a novel allergen in shellfish. In this study, FLN c from Scylla paramamosain was divided into three regions for recombinant expression based on the number of domains and amino acids. Using dot blot and basophil activation tests, the allergic predominant region of FLN c was determined to be 336-531 amino acid positions (named FLN c-M). It was confirmed that by X-ray diffraction, the crystal structure of FLN c-M with immunoglobulin-like folding at a resolution of 1.7 Å was obtained. The monomer was a barrel structure composed of 16 ß-strands and 2 α-helices. Three conformational epitopes were predicted, six linear epitopes were verified by serological test, and they were positioned on the crystal structure of FLN c-M. For the first time, the crystal structure of the allergic predominant region of FLN c was determined, and it provided an accurate template for the localization of IgE epitopes.

Two allergens from Scylla paramamosain share common epitopes showed different allergenic potential in Balb/c mice.

Filamin C (FLN c) and triosephosphate isomerase (TIM) are novel allergens of crab (Scylla paramamosain) which are sharing common epitopes. This work aimed to assess their contributions to the induction and elicitation of allergenic responses. Balb/c mice were sensitized by intraperitoneal injections and challenged by intragastric gavage with purified proteins. Upon oral challenge, FLN c triggered more severe anaphylactic symptoms, higher levels of specific antibodies and histamine in serum than TIM, while TIM was a more active promotor of early specific antibody production and stimulated stronger Th2-biased responses. Combined with the results of in vitro assays, the data demonstrated that though with common epitopes, the two allergens showed a different allergenicity, TIM favored Th2 polarization in sensitization stage, while FLN c had a better ability to stimulate B cells and is highly immunogenic in oral challenge stage. The findings can help with the better understanding of allergenicity of crab allergens.

Analysis of Immunoreactivity of α/α2-Tropomyosin from Haliotis discus hannai, Based on IgE Epitopes and Structural Characteristics.

Tropomyosin (TM) was reported to be a supercoil allergen of shellfish. However, little information is available about its link between structure and allergenicity. In this study, the subunit of TM (α-TM) and supercoil of TM (α2-TM) were identified from Haliotis discus hannai. α2-TM showed higher immunoreactivity than α-TM. Meanwhile, seven linear epitopes in α-TM and α2-TM were verified, and two conformational epitopes in α2-TM were predicted. The physicochemical properties and chemical bond assays confirmed the existence of the disulfide bond in α2-TM. According to spectroscopy and hydrophobicity analysis, α-TM showed higher α-helix features and blueshift of the fluorescence intensity peak compared with those of α2-TM. The structure analysis revealed the possibility of conformational epitopes in α2-TM, which could explain the immunoreactivity differences between α-TM and α2-TM further. These results improved the understanding of Haliotis discus hannai TM, which lay the foundation for the food processing of abalone.

Anagliptin prevented interleukin 1ß (IL-1ß)-induced cellular senescence in vascular smooth muscle cells through increasing the expression of sirtuin1 (SIRT1).

Vascular smooth muscle cell senescence plays a pivotal role in the pathogenesis of atherosclerosis. Anagliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor for the treatment of hyperglycemia. Recent progress indicates that DPP-4 inhibitors show a wide range of cardiovascular benefits. We hypothesize that Anagliptin plays a role in vascular smooth muscle cell senescence and this may imply its modulation of atherosclerosis. Here, the beneficial effect of Anagliptin against interleukin 1ß (IL-1ß)-induced cell senescence in vascular smooth muscle cells was studied to learn the promising therapeutic capacity of Anagliptin on atherosclerosis. Firstly, we found that Anagliptin treatment ameliorated the elevated secretions of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and macrophage chemoattractant protein-1 (MCP-1). Secondly, our findings indicate that exposure to IL-1ß reduced telomerase activity from 26.7 IU/L to 15.8 IU/L, which was increased to 20.3 and 24.6 IU/L by 2.5 and 5 µM Anagliptin, respectively. In contrast, IL-1ß stimulation increased senescence- associated ß-galactosidase (SA-ß-gal) staining to 3.1- fold compared to the control group, it was then reduced to 2.3- and 1.6- fold by Anagliptin dose-dependently. Thirdly, Anagliptin dramatically reversed the upregulated p16, p21, and downregulated sirtuin1 (SIRT1) in IL-1ß-treated vascular smooth muscle cells. Lastly, the protective effect of Anagliptin against cellular senescence in vascular smooth muscle cells was abolished by silencing of SIRT1. In conclusion, Anagliptin protects vascular smooth muscle cells from cytokine-induced senescence, and the action of Anagliptin in vascular smooth muscle cells requires SIRT1 expression.

MicroRNA­181a promotes epithelial­mesenchymal transition in esophageal squamous cell carcinoma via the TGF­ß/Smad pathway.

Esophageal squamous cell carcinoma (ESCC) is one of the most debilitating and invasive tumors. Although previous reports have demonstrated the critical role microRNA­181a (miR­181a) serves in the progression of ESCC, how miR­181a induces epithelial­mesenchymal transition (EMT) remains to be elucidated. In the present study, the expression profiles of TGF­ß1 and Smad4 proteins in 88 patients with ESCC and 21 adjacent non­cancerous tissues were analyzed using immunohistochemistry. The expression of miR­181a in ESCC cells (ECA109 and TE­1) and HEEC was analyzed using reverse transcription­quantitative polymerase chain reaction (RT­qPCR). The role of miR­181a in ESCC was analyzed using miR­181a mimics and inhibitor in the same system. Migration, proliferation and apoptosis of cells were assessed using wound­healing assays and cell proliferation assays and flow cytometry, respectively. The expression levels of TGF­ß1 and Smad4 in ESCC cell lines transfected with miR­181a mimics and inhibitor were measured using RT­qPCR and western blotting. The expression of E­cadherin and vimentin was also assessed following transfection. The findings demonstrated that expression of TGF­ß1 was upregulated, in contrast to Smad4 expression which was downregulated. Expression levels of Smad4 affected the prognosis of patients with ESCC. Higher expression of miR­181a promoted migration and proliferation but inhibited apoptosis of ESCC cells. miR­181a promoted EMT by modulating Smad4 expression in ESCC cells. Overall, these findings revealed that miR­181a induced EMT in ESCC via the TGF­ß/Smad pathway in ESCC. Consequently, miR­181a is a potential novel target against ESCC.

Tracheal stent placement provides opportunity for subsequent anti-cancer therapy for cancer patients with malignant respiratory complications.

BACKGROUND: Critically ill patients with severe acute dyspnea due to malignant tracheal stenosis or tracheoesophageal fistula often need advanced respiratory support. Tracheal stenting is an important palliative treatment of such patients. This study retrospectively analyzes the efficacy and outcomes of airway stenting in patients with tracheal stenosis or tracheoesophageal fistula. METHODS: Patients underwent stenting from 2005 to 2018 in a single center were reviewed. Ninety-seven patients with malignant tracheal stenosis and/or tracheoesophageal fistula who underwent stenting were analyzed, all these patients had poor respiratory status. RESULTS: The median survival time of patients after stent placement was 119 days. Forty-five patients were treated with anti-tumor therapy after placing the stent. Discharged intensive care unit (ICU) within 3 days and postoperative antitumor treatment were independent predictors for the survival time after tracheal stenting (P<0.05). CONCLUSIONS: Tracheal stent implantation played an important role for additional anti-cancer treatment.

Serum suPAR associated with disease severity and mortality in elderly patients with community-acquired pneumonia.

Severe community-acquired pneumonia (SCAP) in elderly has more atypical clinical presentation compared to younger patients. Timely recognition could improve clinical care. This study investigated the value of soluble urokinase-type plasminogen activator receptor (suPAR) on severity assessment and outcome prediction in elderly patients with CAP. We conducted a prospective, observational study between January 2014 and December 2016. A total of 230 patients ≥65 were enrolled in this study, of which 151 were CAP and 79 were SCAP. Serum suPAR levels were determined by ELISA essays within 24 h after hospitalization. Thirty-day and 1-year mortalities were recorded as outcomes. Serum suPAR level was significantly increased in patients with SCAP. Positive correlation was found between suPAR levels with CURB-65 and PSI score (r = 0.423 and r = 0.489; p < .001 for both). The AUC for suPAR to discriminate SCAP patients from CAP was 0.783 at a cut-off value 4.27 ng/mL. AUCs of suPAR for predicting 30-day and 1-year mortalities were 0.815 (95% CI 0.746-0.866) and 0.820 (95% CI 0.770-0.870). Regression result shows suPAR (≥8.92 ng/mL) was independent factor for 30-day mortality (HR = 2.83, 95% CI 1.04-7.69) and suPAR with cut-off value 6.18 ng/mL could predict 1-year mortality (HR = 2.44, 95% CI 1.09-5.44). suPAR was strongly associated with CAP severity and could be a prognostic indicator for 1-year survival in elderly.