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53. Role of Extrapancreatic Necrosis Volume in Assessing the Severity and Predicting the Outcomes of Severe Acute Pancreatitis

Author

Fu,Bao, Feng,Hui, Gao,Fei, and Fu,Xiaoyun

Subjects
CTSI, acute pancreatitis, Ranson score, International Journal of General Medicine, General Medicine, acute necrotic collection, Original Research
Abstract

Bao Fu,1,2,&ast; Hui Feng,1,3,&ast; Fei Gao,1,2 Xiaoyun Fu1,2 1Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi City, Guizhou Province, People’s Republic of China; 2Severe Acute Pancreatitis Diagnosis and Treatment Center of Guizhou Province, Zunyi City, Guizhou Province, People’s Republic of China; 3Department of Critical Care Medicine, Renhuai People’s Hospital, Renhuai City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyun FuDepartment of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Dalian Road149, Zunyi City, Guizhou Province, People’s Republic of ChinaTel +8618108522207Fax +8685128608615Email zyyxyfxy@163.comObjective: To observe the relationship between the extrapancreatic necrosis volume and outcomes in patients with severe acute pancreatitis (SAP).Methods: We retrospectively analyzed 125 patients with SAP admitted to Severe Acute Pancreatitis Treatment Center of Guizhou Province from August 2013 to August 2018. All patients had extrapancreatic necrosis. The general clinical data of patients, C-reactive protein (CRP) value within 72 hours of onset, Ranson score, organ failure within 3 days after onset, complications, outcomes, CT severity index (CTSI), extrapancreatic necrosis volume and other information were collected. The correlation between extrapancreatic necrosis volume and hospitalization time, ICU stay, hospitalization cost, and CRP value was analyzed. The incidence of complications was obtained from the electronic medical record system.Results: The mean extrapancreatic necrosis volume was 680 ± 473 mL. The median length of hospital stay was 18.2 (3– 76) days, and the ICU stay was 13.5 (3– 66) days. The extrapancreatic necrosis volume was positively correlated with hospitalization time, ICU stay time, cost of hospitalization and CRP (P < 0.05). The extrapancreatic necrosis volume in organ failure group was significantly higher than that in non-organ failure group (P < 0.05). The extrapancreatic necrosis volume in patients with death was also higher than that in survival (P < 0.05). With the increase of extrapancreatic necrosis volume, the incidence of complications increased significantly. On the basis of extrapancreatic necrosis volume, the ROC curves yielded an AUC of 0.92 (95% CI: 0.83, 0.99) in predicting the mortality, which was higher than Ranson score (0.90, 95% CI 0.82– 0.96) and CTSI (0.85, 0 95% CI 0.77– 0.91).Conclusion: With the increase of extrapancreatic necrosis volume, the incidence of complications increased significantly. The extrapancreatic necrosis volume has the potential to be used as a valuable tool to predict the poor outcome of acute pancreatitis.Keywords: acute pancreatitis, acute necrotic collection, CTSI, Ranson score

Published
2021

56. Deuterated Linoleic Acid Attenuates the RBC Storage Lesion in a Mouse Model of Poor RBC Storage

Author

Kim, Christopher Y., primary, Johnson, Hannah, additional, Peltier, Sandy, additional, Spitalnik, Steven L., additional, Hod, Eldad A., additional, Francis, Richard O., additional, Hudson, Krystalyn E., additional, Stone, Elizabeth F., additional, Gordy, Dominique E., additional, Fu, Xiaoyun, additional, Zimring, James C., additional, Amireault, Pascal, additional, Buehler, Paul W., additional, Wilson, Robert B., additional, D’Alessandro, Angelo, additional, Shchepinov, Mikhail S., additional, and Thomas, Tiffany, additional

Published
2022
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63. Anticoagulation targeting membrane-bound anionic phospholipids improves outcomes of traumatic brain injury in mice

Author

Dong, Xinlong, primary, Liu, Wei, additional, Shen, Yu, additional, Houck, Katie, additional, Yang, Mengchen, additional, Zhou, Yuan, additional, Zhao, Zilong, additional, Wu, Xiaoping, additional, Blevins, Teri, additional, Koehne, Amanda L., additional, Wun, Tze-Chein, additional, Fu, Xiaoyun, additional, Li, Min, additional, Zhang, Jianning, additional, and Dong, Jing-fei, additional

Published
2021
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69. The lysophospholipid-binding molecule CD1D is not required for the alloimmunization response to fresh or stored RBCs in mice despite RBC storage driving alterations in lysophospholipids

Author

Medved, Jelena, Knott, Brittney M., Tarrah, Soraya N., Li, Andria N., Shah, Neha, Moscovich, Tamara C., Boscia, Alexis R., Salazar, Juan E., Santhanakrishnan, Manjula, Hendrickson, Jeanne E., Fu, Xiaoyun, Zimring, James C., and Luckey, Chance John

Subjects
Male, Isoantigens, Erythrocytes, Ovalbumin, chemical and pharmacologic phenomena, Mice, Inbred Strains, Mice, Transgenic, Receptors, Cell Surface, Article, Mass Spectrometry, Mice, Antibody Specificity, Isoantibodies, Alarmins, Animals, Blood Transfusion, Mice, Knockout, Transfusion Reaction, hemic and immune systems, Immunoglobulin M, Blood Preservation, Immunoglobulin G, lipids (amino acids, peptides, and proteins), Female, Immunization, Muramidase, Antigens, CD1d, Lysophospholipids, Duffy Blood-Group System
Abstract

BACKGROUND: Despite the significant adverse clinical consequences of RBC alloimmunization, our understanding of the signals that induce immune responses to transfused RBCs remains incomplete. Though RBC storage has been shown to enhance alloimmunization in the hen egg lysozyme, ovalbumin, and human Duffy (HOD) RBC alloantigen mouse model, the molecular signals leading to immune activation in this system remain unclear. Given that the nonclassical major histocompatibility complex (MHC) Class I molecule CD1D can bind to multiple different lysophospholipids and direct immune activation, we hypothesized that storage of RBCs increases lysophospholipids known to bind CD1D, and further that recipient CD1D recognition of these altered lipids mediates storage-induced alloimmunization responses. STUDY DESIGN AND METHODS: We used a mass spectrometry-based approach to analyze the changes in lysophospholipids that are induced during storage of mouse RBCs. CD1D knockout (CD1D-KO) and wild-type (WT) control mice were transfused with stored HOD RBCs to measure the impact of CD1D deficiency on RBC alloimmunization. RESULTS: RBC storage results in alterations in multiple lysophospholipid species known to bind to CD1D and activate the immune system. Prior to transfusion, CD1D-deficient mice had lower baseline levels of polyclonal immunoglobulin (IgG) relative to WT mice. In response to stored RBC transfusion, CD1D-deficient mice generated similar levels of anti-HOD IgM and anti-HOD IgG. CONCLUSION: Although storage of RBCs leads to alteration of several lysophospholipids known to be capable of binding CD1D, storage-induced RBC alloimmunization responses are not impacted by recipient CD1D deficiency.

Published
2021

70. Prediction of infected pancreatic necrosis in acute necrotizing pancreatitis by the modified pancreatitis activity scoring system

Author

Mao, Wenjian, Li, Kang, Zhou, Jing, Chen, Miao, Ye, Bo, Li, Gang, Singh, Vikesh, Buxbaum, James, Fu, Xiaoyun, Tong, Zhihui, Liu, Yuxiu, Windsor, John, Li, Weiqin, and Ke, Lu

Abstract

Infected pancreatic necrosis (IPN) is a significant complication of acute necrotizing pancreatitis (ANP). Early identification of patients at high risk of IPN would enable appropriate treatment, but there is a lack of valid tools. This study aimed to assess the performance of the Pancreatitis Activity Scoring System (PASS) and its modifications (by removing or reducing the weight of opioid usage) in predicting IPN in a cohort of predicted severe ANP patients. Data was prospectively collected in the TRACE trial (2017–2020) involving 16 sites across China. The predictive performance of PASS, modified PASS (mPASS), and conventional indices were assessed by the area under the receiver operating characteristic curve (AUC), Hosmer‐Lemeshow Ĉ‐test, Brier score, and Fagan's nomogram. Multivariate logistic regression analysis (MLRA) was used to define the relationship between the best‐performing PASS/mPASS model and IPN. A total of 508 subjects were enrolled (median age, 43 years; 62.8% males) in the original trial, and 122 developed IPN (24%) within 90 days after randomization. Compared with non‐IPN patients, the scores of PASS and its modified models were significantly higher in the IPN patients (all p< 0.001). Among the PASS and its modifications, mPASS‐4 had the largest AUC, the lowest Brier score, and good calibration. The mPASS‐4 model demonstrated an AUC of 0.752 in predicting IPN (the optimal cut‐off for the mPASS‐4 was 292.5) and outperformed the conventional indices. The MLRA results showed that mPASS‐4 >292.5 was an independent risk factor of IPN (OR: 3.6, 95% CI: 2.1–6.3). The PASS and its modifications during the first week of ANP onset predict the development of IPN, with mPASS‐4 performing best. The mPASS‐4 model simplifies the original PASS, increasing the likelihood of clinical implementation.

Published
2023
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74. Synthesis and biological evaluation of novel disulfides incorporating 1,3,4-thiadiazole scaffold as promising antitumor agents

Author

Fu Xiaoyun, Fen Jing, Bao-Quan Chen, Hai-Xin Wang, Sha Li, Shi Yanping, Hai-Ying Liu, and Cai-Wen Li

Subjects
A549 cell, Scaffold, 010405 organic chemistry, Cell growth, Chemistry, Organic Chemistry, 01 natural sciences, Combinatorial chemistry, In vitro, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, Thiadiazoles, Bioassay, Potency, General Pharmacology, Toxicology and Pharmaceutics, IC50
Abstract

In the present study, fourteen 2,5-disubstituted 1,3,4-thiadiazole derivatives containing disulfide group were prepared. The resulting compounds 7a–7n were identified by IR, NMR, MS, and elemental analysis. Their antiproliferative properties in vitro were studied employing standard CCK-8 assay against SMMC-7721, MCF-7, and A549 lines. Bioassay indicated that some compounds showed stronger antitumor effects than reference drugs PX-12 and 5-fluorouracil. Among these screened compounds, compound 7h showed excellent biological activities in inhibiting SMMC-7721 cell proliferation with IC50 at 1.93 ± 0.08 μM. Compounds 7k and 7i manifested highly effective growth inhibitory activity versus MCF-7 cells, with IC50 at 3.04 ± 0.09 and 3.54 ± 0.17 μM, respectively. For A549 cells, compound 7m was found to have the highest antitumor potency with IC50 at 3.67 ± 0.13 μM.

Published
2019

76. The lysophospholipid‐binding molecule CD1D is not required for the alloimmunization response to fresh or stored RBCs in mice despite RBC storage driving alterations in lysophospholipids

Author

Medved, Jelena, primary, Knott, Brittney M., additional, Tarrah, Soraya N., additional, Li, Andria N., additional, Shah, Neha, additional, Moscovich, Tamara C., additional, Boscia, Alexis R., additional, Salazar, Juan E., additional, Santhanakrishnan, Manjula, additional, Hendrickson, Jeanne E., additional, Fu, Xiaoyun, additional, Zimring, James C., additional, and Luckey, Chance John, additional

Published
2021
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77. Hematologic and systemic metabolic alterations due to Mediterranean class II G6PD deficiency in mice

Author

D’Alessandro, Angelo, primary, Howie, Heather L., additional, Hay, Ariel M., additional, Dziewulska, Karolina H., additional, Brown, Benjamin C., additional, Wither, Matthew J., additional, Karafin, Matthew, additional, Stone, Elizabeth F., additional, Spitalnik, Steven L., additional, Hod, Eldad A., additional, Francis, Richard O., additional, Fu, Xiaoyun, additional, Thomas, Tiffany, additional, and Zimring, James C., additional

Published
2021
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78. Hematologic and systemic metabolic alterations due to Mediterranean type II G6PD deficiency in mice

Author

D’Alessandro, Angelo, primary, Howie, Heather L, additional, Hay, Ariel M., additional, Dziewulska, Karolina H., additional, Brown, Benjamin, additional, Wither, Matthew J, additional, Karafin, Matthew, additional, Stone, Elizabeth F., additional, Spitalnik, Steven L, additional, Hod, Eldad A, additional, Francis, Richard O, additional, Fu, Xiaoyun, additional, Thomas, Tiffany, additional, and Zimring, James C, additional

Published
2021
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79. Arterial Platelet Adhesion in Atherosclerosis‐Prone Arteries of Obese, Insulin‐Resistant Nonhuman Primates

Author

Brown, Eran, primary, Ozawa, Koya, additional, Moccetti, Federico, additional, Vinson, Amanda, additional, Hodovan, James, additional, Nguyen, The Anh, additional, Bader, Lindsay, additional, López, José A., additional, Kievit, Paul, additional, Shaw, Gray D., additional, Chung, Dominic W., additional, Osborn, Warren, additional, Fu, Xiaoyun, additional, Chen, Junmei, additional, and Lindner, Jonathan R., additional

Published
2021
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80. The biological activity of FasL in human and mouse lungs is determined by the structure of its stalk region

Author

Herrero, Raquel, Kajikawa, Osamu, Matute-Bello, Gustavo, Wang, Yi, Hagimoto, Naoki, Mongovin, Steve, Wong, Venus, Park, David R., Brot, Nathan, Heinecke, Jay W., Rosen, Henry, Goodman, Richard B., Fu, Xiaoyun, and Martin, Thomas R.

Subjects
Lung diseases -- Diagnosis -- Care and treatment -- Research, Body fluids -- Physiological aspects -- Research -- Health aspects, Bronchoalveolar lavage -- Health aspects -- Physiological aspects -- Research, Health care industry
Abstract

Acute lung injury (ALI) is a life-threatening condition in critically ill patients. Injury to the alveolar epithelium is a critical event in ALI, and accumulating evidence suggests that it is linked to proapoptotic Fas/FasL signals. Active soluble FasL (sFasL) is detectable in the bronchoalveolar lavage (BAL) fluid of patients with ALI, but the mechanisms controlling its bioactivity are unclear. We therefore investigated how the structure of sFasL influences cellular activation in human and mouse lungs and the role of oxidants and proteases in modifying sFasL activity. The sFasL in BAL fluid from patients with ALI was bioactive and present in high molecular weight multimers and aggregates. Oxidants generated from neutrophil myeloperoxidase in BAL fluid promoted aggregation of sFasL in vitro and in vivo. Oxidation increased the biological activity of sFasL at low concentrations but degraded sFasL at high concentrations. The amino-terminal extracellular stalk region of human sFasL was required to induce lung injury in mice, and proteolytic cleavage of the stalk region by MMP-7 reduced the bioactivity of sFasL in human cells in vitro. The sFasL recovered from the lungs of patients with ALI contained both oxidized methionine residues and the stalk region. These data provide what we believe to be new insights into the structural determinants of sFasL bioactivity in the lungs of patients with ALI., Introduction Acute lung injury (ALI), including its more severe form, acute respiratory distress syndrome (ARDS), is common in critically ill patients and carries an overall mortality of 40% or higher [...]

Published
2011
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81. Methionine oxidation contributes to bacterial killing by the myeloperoxidase system of neutrophils

Author

Rosena, Henry, Klebanoff, Seymour J., Wang, Yi, Brot, Nathan, Heinecke, Jay W., and Fu, Xiaoyun

Subjects
Methionine -- Properties, Peroxidase -- Properties, Neutrophils -- Properties, Anti-infective agents -- Composition, Immunological research -- Methods, Science and technology
Abstract

Reactive oxygen intermediates generated by neutrophils kill bacteria and are implicated in inflammatory tissue injury, but precise molecular targets are undefined. We demonstrate that neutrophils use myeloperoxidase (MPO) to convert methionine residues of ingested Escherichia coli to methionine sulfoxide in high yield. Neutrophils deficient in individual components of the MPO system (MPO, H202, chloride) exhibited impaired bactericidal activity and impaired capacity to oxidize methionine. HOCI, the principal physiologic product of the MPO system, is a highly efficient oxidant for methionine, and its microbicidal effects were found to correspond linearly with oxidation of methionine residues in bacterial cytosolic and inner membrane proteins. In contrast, outer envelope proteins were initially oxidized without associated microbicidal effect. Disruption of bacterial methionine sulfoxide repair systems rendered E. coli more susceptible to killing by HOCI, whereas over-expression of a repair enzyme, methionine sulfoxide reductase A, rendered them resistant, suggesting a direct role for methionine oxidation in bactericidal activity. Prominent among oxidized bacterial proteins were those engaged in synthesis and translocation of peptides to the cell envelope, an essential physiological function. Moreover, HOCI impaired protein translocation early in the course of bacterial killing. Together, our findings indicate that MPO-mediated methionine oxidation contributes to bacterial killing by neutrophils. The findings further suggest that protein translocation to the cell envelope is one important pathway targeted for damage. bactericidal | microbicidal www.pnas.org/cgi/doi/10.1073/pnas.0909464106

Published
2009

82. Fatty acid desaturase activity in mature red blood cells and implications for blood storage quality

Author

Thomas, Tiffany, primary, Cendali, Francesca, additional, Fu, Xiaoyun, additional, Gamboni, Fabia, additional, Morrison, Evan J., additional, Beirne, Jonathan, additional, Nemkov, Travis, additional, Antonelou, Marianna H., additional, Kriebardis, Anastasios, additional, Welsby, Ian, additional, Hay, Ariel, additional, Dziewulska, Karolina H., additional, Busch, Michael P., additional, Kleinman, Steven, additional, Buehler, Paul W., additional, Spitalnik, Steven L., additional, Zimring, James C., additional, and D'Alessandro, Angelo, additional

Published
2021
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85. Bi-directional evolutionary topology optimization for designing a neutrally buoyant underwater glider

Author

Tengfei Tang, Baoren Li, Gang Yang, Yi Xi, and Fu Xiaoyun

Subjects
Control and Optimization, 010505 oceanography, Computer science, Underwater glider, Applied Mathematics, Hull structure, Topology optimization, 0211 other engineering and technologies, Glider, 02 engineering and technology, Management Science and Operations Research, 01 natural sciences, Industrial and Manufacturing Engineering, Finite element method, Computer Science Applications, Neutral buoyancy, Hull, 021106 design practice & management, 0105 earth and related environmental sciences, Marine engineering
Abstract

An underwater glider is a type of autonomous profiling instrument platform used for gathering data to explore the ocean. Having a neutrally buoyant glider hull is one way to improve the glider's en...

Published
2017

92. Bcl-x(sub)L deamidation is a critical switch in the regulation of the response to DNA damage

Author

Deverman, Benjamin E., Cook, Brian L., Manson, Scott R., Niederhoff, Robert A., Langer, Ellen M., Rosova, Ivana, Kulans, Laura A., Fu, Xiaoyun, Weinberg, Justin S., Heinecke, Jay W., Roth, Kevin A., and Weintraub, Steven J.

Subjects
DNA damage -- Physiological aspects, Cancer cells -- Physiological aspects, Cell death -- Physiological aspects, Structure-activity relationships (Biochemistry) -- Analysis, Biological sciences
Abstract

Results reveal that the deamidation of two asparagines in the Bcl-x(sub)L gene renders tumor cells susceptible to apoptosis by inhibiting the gene's ability to block the proapoptotic activity of BH3 domain-only proteins leading to the DNA damage-induced apoptosis.

Published
2002

93. Generation of intramolecular and intermolecular sulfenamides, sulfinamides, and sulfonamides by hypochlorous acid: a potential pathway for oxidative cross-linking of low-density lipoprotein by myeloperoxidase

Author

Fu, Xiaoyun, Mueller, Dianne M., and Heinecke, Jay W.

Subjects
Proteins -- Crosslinking, Low density lipoproteins -- Physiological aspects, Hemoproteins -- Physiological aspects, Sulfonamides -- Physiological aspects, Atherosclerosis -- Research, Biological sciences, Chemistry
Abstract

Research shows that the myeloperoxidase heme protein generated hypochlorous acid produces intramolecular sulfenamides, sulfinamides, and sulfonamides and intermolecular sulfonamides from the low-density lipoprotein thiol and amino groups. Data indicate that myeloperoxidase mediates protein cross-linking in the artery wall during atherogenesis.

Published
2002

98. Impact of taurine on red blood cell metabolism and implications for blood storage

Author

Bertolone, Lorenzo, primary, Roy, Micaela Kalani, additional, Hay, Ariel M., additional, Morrison, Evan J., additional, Stefanoni, Davide, additional, Fu, Xiaoyun, additional, Kanias, Tamir, additional, Kleinman, Steve, additional, Dumont, Larry J., additional, Stone, Mars, additional, Nemkov, Travis, additional, Busch, Michael P., additional, Zimring, James C., additional, and D'Alessandro, Angelo, additional

Published
2020
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100. Differential Metabolomics and Lipidomics of Hypoxic/Hypocapnic Long-Term Stored Red Cells Associate with Improved 24-Hour Recovery after Transfusion

Author

Yoshida, Tatsuro, primary, D'Alessandro, Angelo, additional, Fu, Xiaoyun, additional, Nemkov, Travis, additional, Stefanoni, Davide, additional, Dioguardi, Michael, additional, Rugg, Neeta, additional, Nestheide, Shawnagay, additional, Iselin, William, additional, Dunham, Andrew, additional, Zimring, James C., additional, and Cancelas, Jose A, additional

Published
2019
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