doi:10.1016/j.antiviral.2006.04.014, Hofer, C. C., Woods, P. S., and Davis, I. C. (2015). The imbalance of fluid metabolism, pulmonary fluid clearance (PFC) and rich-protein fluid entrance, may be a key reason for the acute exacerbation of pulmonary edema in COVID-19 patients. Improving the blood circulation can advance the oxygen supply for organs, accelerate the absorption of fluid and eventually improve pulmonary edema. doi:10.1165/ajrcmb.20.5.3382, Pascarella, G., Strumia, A., Piliego, C., Bruno, F., Del Buono, R., Costa, F., et al. Pharmacol. doi:10.1161/01.cir.37.1.45, Cai, J., Li, H., Zhang, C., Chen, Z., Liu, H., Lei, F., et al. Copyright 2021 Cui, Chen, Zhou, Gong, Zhu, Lv, Guo, Duan, Zhou, Marcon and Ma. Currently, these symptoms are the primary consequences of pulmonary virus infection. Chemical Composition and Pharmacological Mechanism of Qingfei Paidu Decoction and Ma Xing Shi Gan Decoction against Coronavirus Disease 2019 (COVID-19): In Silico and Experimental Study. Reaffirms recommendation for Janssen COVID-19 Vaccine. Rev. Allergy Clin. doi:10.1056/NEJMoa2028836, Tang, Y., Liu, J., Zhang, D., Xu, Z., Ji, J., and Wen, C. (2020). Crit. Moreover, other drugs which can regulate immune system like hydroxychloroquine and azithromycin may also show effects in treating SARS-COV-2-induced pulmonary edema and their effectiveness in treating SARS-COV-2 infections should be further investigated. (2018). Rev. Infection, pulmonary edema, lung cancer, aspiration, and pulmonary hemorrhage are some of the diseases that can cause consolidation. J. Physiol. Currently, only icatibant has been approved as bradykinin antagonist for clinical treatment, and relevant studies have revealed that cefepime, cefpirome, imatinib, raloxifene, sildenafil, ponatinib, abemaciclib and entrectinib may also act as prospective non-selective bradykinin antagonists and have potential for treatment of COVID-19 (Rasaeifar et al., 2020). When there, the virus itself and virus-mediated protein-protein interactions lead to the lung inflammatory storm responsible for the observed increasing vascular permeability in lung and pulmonary edema (Tang et al., 2020). A., Hsieh, C.-L., Abiona, O., et al. Is Amiloride a Promising Cardiovascular Medication to Persist in the COVID-19 Crisis?. doi:10.1152/ajplung.00376.2005, Li, C., Wang, P., Li, M., Zheng, R., Chen, S., Liu, S., et al. Negative-feedback Loop Attenuates Hydrostatic Lung Edema via a cGMP-dependent Regulation of Transient Receptor Potential Vanilloid 4. He had no cough, expectoration, nasal discharge or sore throat. Multiple TCMs have been already clinical applied for COVID-19 in China and achieved high recovery rate. Res. Nat. 2, 1019. (2020). 308 (7), L628L638. (2014). Additionally, other major ADRs were potentially linked to the BNT162b2 mRNA COVID-19 vaccine, including central nervous system thrombosis, deep vein thrombosis, and pulmonary embolism [3-5]. Am. Biophys. 16 (10), 17081717. Infection and replication process of SARS-CoV-2. FIGURE 4. Vaccines (Basel). Cause of COVID-19 pulmonary edema. Heart Circ. (2020). Like all medicines, the coronavirus (COVID-19) vaccines can cause side effects. J. Investig. Inhibiting these TRPs may benefit the treatment of pulmonary edema. J. Physiology-Lung Cell Mol. (2020). However, palpable lymphadenopathy commonly involving the axilla as an immune response to vaccination may present a clinical diagnostic dilemma especially in persons with . In addition, natural compounds and TCMs which generally have multiple targets should also be investigated, both in terms of their efficacy and safety. 2021 May 7;8:644678. doi: 10.3389/fmed.2021.644678. (2020). As reported, large-conductance calcium-activated potassium channels (BKCa) in alveoli can reduce alveoli opening during hypoxia, detect O2 variation, and adjust ion transport and fluid clearance (Jovanovi et al., 2003). Mil. 288, 198114. doi:10.1016/j.virusres.2020.198114, Krlicka, A. L., Kruczkowska, A., Krajewska, M., and Kusztal, M. A. Proteoglycan Involvement during Development of Lesional Pulmonary Edema. Meanwhile, the number of patients in the treatment group presenting improved PaO2/FiO2 and ROX index was higher than that of the control group (95.2% vs. 68.4% and 73.7%). It not only can induce de novo synthesis of ENaC and affect ENaC regulatory pathway, but also has an impact on cytokines. As the activation of AT1 receptor promotes the pulmonary edema, AT1 receptor blockers (ARBs) like losartan, valsartan may be effective in decreasing pulmonary edema. (2009). doi:10.1152/ajplung.00244.2017, Looney, M. R., Sartori, C., Chakraborty, S., James, P. F., Lingrel, J. Here, we provide a perspective on abnormal lung humoral metabolism of pulmonary edema in COVID-19 patients, review the mechanisms by which pulmonary edema may be induced in COVID-19 patients, and propose putative drug targets that may be of use in treating COVID-19. Quantitative mRNA Expression Profiling of ACE 2, a Novel Homologue of Angiotensin Converting Enzyme. Emodin, an anthraquinone compound from genus Rheum and Polygonum, can markedly prevent the binding of S protein and ACE2 in the study of SARS-CoV (Ho et al., 2007). J. Endocrinol. Federal government websites often end in .gov or .mil. Fedratinib, an FDA approved JAK2 inhibitor, may be used to reduce the mortality associated with hyperinflammation by suppressing the production of several Th17 cytokines (i.e., IL1b and TNF-alpha, IL21, IL22, IL17) and the formation of pulmonary edema in combination with anti-viral drugs (Yang et al., 2020e). 276 (22), 1865718664. Respir. Endocrinology in the Time of COVID-19: Management of Diabetes Insipidus and Hyponatraemia. MeSH Cepharanthine: a Review of the Antiviral Potential of a Japanese-approved Alopecia Drug in COVID-19. In COVID-19 patients, pulmonary edema is diagnosed by lung ultrasound and a computerized tomography (CT) scan (Udugama et al., 2020). B., and Matthay, M. A. Am. Nonetheless, little attention has been paid to CD44 in COVID-19 treatment. 157, 104882. doi:10.1016/j.phrs.2020.104882, Zhang, H., and Baker, A. doi:10.1002/jcp.28602, Otulakowski, G., Rafii, B., Bremner, H. R., and O'Brodovich, H. (1999). Sci. Studies showed that ENaC activators or stimulators can regulate ENaC-dependent fluid absorption in alveolar and pulmonary edema (Fronius, 2013). With treatment, most people with this type of pulmonary edema recover in about 24 hours. 2, 26372646. Inhalation or infusion of salbutamol, a 2-adrenergic agonist, reduced the incidences of pulmonary edema (Sartori et al., 2002) and was found to be beneficial in ARDS patients (Perkins et al., 2006). The Lancet 395 (10223), 497506. XC analyzed and reviewed the research articles as well as drafting the manuscript. Ursodeoxycholic Acid Stimulates Alveolar Fluid Clearance in LPSinduced Pulmonary Edema via ALX/cAMP/PI3K Pathway. 388 (4), 421436. Mechanism of BK inducing pulmonary edema and potential drugs. Aldosterone-induced Sgk1 Relieves Dot1a-Af9-Mediated Transcriptional Repression of Epithelial Na+ Channel . J. Clin. COVID-19, an infectious disease caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a global reach. Gut 69 (6), 10101018. Clinical Course and Outcomes of Critically Ill Patients with SARS-CoV-2 Pneumonia in Wuhan, China: a Single-Centered, Retrospective, Observational Study. Thromb. Circuits between Infected Macrophages and T Cells in SARS-CoV-2 Pneumonia. 108 (6), 11851194. Chem. (2020). Antiviral Res. Phytomedicine 85, 153242. doi:10.1016/j.phymed.2020.153242, Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., et al. J. Physiology-Lung Cell Mol. In the meantime, we urgently need potent reduction in fatality of COVID-19. (2020). Clin. doi:10.1073/pnas.160041997, Leroy, C., Priv, A., Bourret, J.-C., Berthiaume, Y., Ferraro, P., and Brochiero, E. (2006). Physiol. Rev. AQP-5 plays a significant role in pulmonary edema and decreased expression of AQP-5 has been observed during the disease process. Direct Vascular Effects of Furosemide in Humans. 532 (1), 4. doi:10.1016/s0014-5793(02)03640-2, Heald-Sargent, T., and Gallagher, T. (2012). J. Med. (2020). Potassium channels up-regulate ENaC expression via activating KvLQT1 pathway so as to control AFC (Bardou et al., 2012). FIGURE 2. J. Physiology-Lung Cell Mol. People with pneumonia, lung cancer, or heart disease may experience chest pain or wheezing. (2001). Clin. Traditional Chinese Medicine for COVID-19 Treatment. doi:10.1111/nyas.14472, Adil, M. S., Narayanan, S. P., and Somanath, P. R. (2020). Am. 308 (11), L1178L1188. [Effect of Astragali Radix in Improving Early Renal Damage in Metabolic Syndrome Rats through ACE2/Mas Pathway]. Virol. J. Ethnopharmacology 265, 113301. doi:10.1016/j.jep.2020.113301, Li, F. (2016). Potassium channels are usually involved in maintaining the reabsorption of Na+ and the steady state of electrochemical gradient, ions and body fluids in airway epithelial cells specifically. Infection of Mice with Influenza A/WSN/33 (H1N1) Virus Alters Alveolar Type II Cell Phenotype. KCa3.1 (1-EBIO) and KATP (minoxidil) channel openers can greatly recover AFC in mice intratracheally administrated verapamil, which is the first generation of the phenylalkylamine class of calcium channel antagonists (Fleckenstein, 1977; Nayler and Dillon, 1986), suggesting that K+ channel openers might be potential drugs for treating pulmonary edema (Han et al., 2010). doi:10.1530/EJE-20-0338, Clapham, D. E., Runnels, L. W., and Strbing, C. (2001). Urgent reconsideration of lung edema as a preventable outcome in COVID-19: inhibition of TRPV4 represents a promising and feasible approach. Chin. SN Compr. Authors JAMA 249 (2), 237241. J. Cel Physiol 235 (12), 95109523. Alveolar macrophage dysfunction and cytokine storm in the pathogenesis of two severe COVID-19 patients. The Pfizer study defined their primary endpoint as cases of symptomatic, confirmed COVID-19 occurring at least seven days after the second injection, while Moderna counted symptomatic, confirmed COVID-19 cases occurring at least 14 days after the second injection. During the infection of SARS-CoV-2, RAS, BK and hyaluronic acid (HA) are all involved in the regulation of AFC and the formation of pulmonary edema (Garvin et al., 2020). doi:10.1074/jbc.M608358200, Harmer, D., Gilbert, M., and Borman, R. (2002). (2018). Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized with COVID-19 in the New York City Area. It has been reported that infection with a respiratory-associated virus can significantly increase the expression and activity of TRPV1 (Abdullah et al., 2014). Sci. 2023 Feb 15;12(4):1542. doi: 10.3390/jcm12041542. Moreover, the peripheral blood mononuclear lymphocyte of COVID-19 patients was also greatly improved, from 0.91 0.54 to 1.24 0.67 after being treated for a week, while there was no obvious change in control group (Hu et al., 2020). FIGURE 3. Calcium Antagonists and Their Mode of Action: an Historical Overview. TRPs in Tox: Involvement of Transient Receptor Potential-Channels in Chemical-Induced Organ Toxicity-A Structured Review. Treatment of 5 Critically Ill Patients with COVID-19 with Convalescent Plasma. medRxiv. Bookshelf A recent review has summarized the effects of TRPs in pulmonary chemical injuries, which includes the representative TRPA1, TRPV1 and TRPV4 antagonists which have participated in preclinical and clinical studies (Achanta and Jordt, 2020) (Supplementary Tables S1S3). Epub 2020 May 13. Pharmacol. doi:10.1038/s41418-020-0530-3, Shi, Z., Ye, W., Zhang, J., Zhang, F., Yu, D., Yu, H., et al. Arek Sarkissian. Naunyn-schmiedeberg's Arch. doi:10.1016/j.cell.2020.02.058, Wang, D., Hu, B., Hu, C., Zhu, F., Liu, X., Zhang, J., et al. TRPA1 Agonists Evoke Coughing in guinea Pig and Human Volunteers. The TRP Ion Channel Family. We identified pulmonary edema, pleural effusion, and pericardial effusion. Natural compounds can inhibit the binding between the virus and the ACE2 receptor of host cells. According to previous studies, activation of AT1 receptor inhibits AFC by down-regulating cAMP and dysregulating ENaC expression, leading to Ang II-dependent pulmonary edema and alveolar filling increase (Deng et al., 2012). Pulmonary edema is the disequilibrium between formation and reflux of lung tissue fluid leading to the absorption of massive tissue fluid by lung lymph and vein failure. J. Respir. 34 (4), 610618. Abnormal humoral metabolism is mainly manifested as imbalances of water and electrolytes. As the infection progresses, the immune function is impaired, causing damage to multiple organs, additional complications, and eventually death (Yang et al., 2020). Rev. 19 (5), 305306. Patients in intensive care units (ICU) have higher plasma levels of IL2, IL7, IL10, MCP1, MIP1A, GSCF, IP10, and TNF (Huang et al., 2020). doi:10.1016/s1875-5364(18)30123-7, Zhang, D., Zhang, B., Lv, J.-T., Sa, R.-N., Zhang, X.-M., and Lin, Z.-J. Chloride Transport-Driven Alveolar Fluid Secretion Is a Major Contributor to Cardiogenic Lung Edema. (2020). J. Nat. FOIA (1997). Patients receive high-flow nasal cannula (HFNC), non-invasive ventilation (NIV), mechanical ventilation or ECMO as respiratory supports (Guo et al., 2020; Pascarella et al., 2020), a crystalloid fluid to ensure body fluid equilibrium (Christ-Crain et al., 2020), and anticoagulants for restraining the thrombus formation to aid in circulatory support (Connors and Levy, 2020). Abstract Background Severe cardiogenic pulmonary edema is a . K+ Channel Openers Restore Verapamil-Inhibited Lung Fluid Resolution and Transepithelial Ion Transport. It promotes the clearance of surplus fluid in alveoli and keeps alveolar space dry (Wittekindt and Dietl, 2019). Br. Recombinant Human ACE2: Acing Out Angiotensin II in ARDS Therapy. FIGURE 5. Lipoxin A4 (LXA4) can stabilize the permeability of pulmonary microvascular endothelial cell by regulating the expression of AQP-5 and MMP-9, and reduce alveolar fluid exudation (Shi et al., 2018). The Potential Chemical Structure of antiSARSCoV2 RNAdependent RNA Polymerase. Structure and Hormone Responsiveness of the Gene Encoding the -Subunit of the Rat Amiloride-Sensitive Epithelial Sodium Channel. COVID-DSNet: A novel deep convolutional neural network for detection of coronavirus (SARS-CoV-2) cases from CT and Chest X-Ray images. Crit. It is worth mentioning that, except alveoli, which is widely known as the target tissue, cardiomyocyte can be infected as well. (2020). Tumor Necrosis Factor- Inhibits Aquaporin 5 Expression in Mouse Lung Epithelial Cells. Immunopharmacology and Immunotoxicology 36 (6), 420425. J. Physiology-Lung Cell Mol. We observed a case of a delayed local reaction in a 38-year-old woman who had received the first dose of the BNT162b2 vaccine. annals 99 (1), 1216. RNA-dependent RNA polymerase (RdRp) is a crucial protease that catalyzes RNA replication from RNA templates and is an appealing therapeutic target. 2, 26372646. Cryptotanshinone Inhibits Endothelin-1 Expression and Stimulates Nitric Oxide Production in Human Vascular Endothelial Cells. Res. Am. Transl. (2020b). The Origin, Transmission and Clinical Therapies on Coronavirus Disease 2019 (COVID-19) Outbreak - an Update on the Status. The available adenoviral vaccines appear to stimulate autoantibodies to platelet factor 4 (PF4), which . Impaired Breakdown of Bradykinin and its Metabolites as a Possible Cause for Pulmonary Edema in COVID-19 Infection. These channels are important in maintaining the optimum volume and ion constitution of bronchial periciliary fluid and alveolar lining fluid layers, which are necessary in appropriate pathogens mucociliary clearance and optimum gas exchange, respectively (Londino et al., 2017). 99 (9), 988995. doi:10.1001/jama.2020.12839, Wittekindt, O. H., and Dietl, P. (2019). Here, we summarized several natural compounds and TCM formulas which are very likely to be potential drugs or have already shown predominant efficacy of COVID-19 patients. When SARS-COV-2 invades, vascular endothelial cells are damaged, causing insufficient arterial flow and minimal thrombus. Perplexingly, among the currently pursued therapeutic strategies against COVID-19, none is designed to directly protect the alveolo-capillary barrier. doi:10.1152/ajplung.1998.275.2.L414, Mutlu, G. M., Dumasius, V., Burhop, J., McShane, P. J., Meng, F. J., Welch, L., et al. doi:10.1016/j.jacbts.2021.01.002, Bardou, O., Priv, A., Migneault, F., Roy-Camille, K., Dagenais, A., Berthiaume, Y., et al. Hormonal Regulation and Genomic Organization of the Human Amiloride-Sensitive Epithelial Sodium Channel Subunit Gene. doi:10.1007/s00424-018-2232-y, Woods, P. S., Tazi, M. F., Chesarino, N. M., Amer, A. O., and Davis, I. C. (2015). Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19). (2020c). Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation. Dexmedetomidine Alleviates Pulmonary Edema by Upregulating AQP1 and AQP5 Expression in Rats with Acute Lung Injury Induced by Lipopolysaccharide. Diagnosing COVID-19: The Disease and Tools for Detection. Semin. As of Sunday, at least 16,183 people had filed complaints with the Centers for Disease Control and Prevention that they'd developed tinnitus, or ringing in their ears, after receiving a Covid vaccine. Symptoms that are common to all of these conditions include cough and shortness of breath. The first treatment for acute pulmonary edema is oxygen. doi:10.1101/2020.03.02.20029975, Yin, J., Hoffmann, J., Kaestle, S. M., Neye, N., Wang, L., Baeurle, J., et al. 310 (10), L928L939. Resolving D1 (Wang et al., 2014), generated from -3 fatty docosahexaenoic acids, and ursodeoxycholic acid (Niu et al., 2019) can stimulate AFC and Na-K-ATPase in LPS-induced pulmonary edema via alveolar epithelial sodium channel and ALX/cAMP/PI3K pathway, respectively. Anti-hypertensive Angiotensin II Receptor Blockers Associated to Mitigation of Disease Severity in Elderly COVID-19 Patients. It has been revealed that COVID-19 patients treated with Lian-Hua-Qing-Wen capsules for 14days resulted in a considerably higher recovery rate of 91.5%, a dramatically shorter median time to symptom recovery of 7days than the control group, which applied conventional treatment (Hu et al., 2021). Systemic Reactions. 54 (10), 774780. Xue-Bi-Jing injection may act in COVID-19 by anti-inflammatory, anticoagulation, immune regulation, vascular endothelial protection, anti-oxidative stress and other mechanisms (Li et al., 2021). IFN will continually induce inflammatory cytokines released by alveolar macrophages, promoting the activation of T cells and forming a positive feedback loop that drives persistent alveolar inflammation (Grant et al., 2021). The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphar.2021.664349/full#supplementary-material, Abdullah, H., Heaney, L. G., Cosby, S. L., and McGarvey, L. P. A. 275 (2), L414L422. -, Adil M. S., Narayanan S. P., Somanath P. R. (2020). TRPA1 distributes on C-fibers throughout the respiratory system (De Logu et al., 2016). Circulation 37 (1), 4553. doi:10.1097/CM9.0000000000000797, Ferner, R. E., and Aronson, J. K. (2020). Viruses 4 (4), 557580. (2019). Prc, N. H. C. o. t. (2020). (2020). Sci. 173 (3), 281287. There are also several natural compounds which were previously shown to have positive effects on the lung edema-associated targets described in this paper (Zhou et al., 2006; Ho et al., 2007; Ji et al., 2014; Wang et al., 2015; Qu, 2019; Fan et al., 2020; Lung et al., 2020). Am. A vision of coronavirus with the minimal set of structural proteins. The clinical manifestations and CT scans show the presence of ARDS in critical COVID-19 patients (Ai et al., 2020; Guan et al., 2020; Huang et al., 2020). Lianhuaqingwen Exerts Anti-viral and Anti-inflammatory Activity against Novel Coronavirus (SARS-CoV-2). Involvement of Lung Interstitial Proteoglycans in Development of Hydraulic- and Elastase-Induced Edema. Role of Transient Receptor Potential Vanilloid 4 in Neutrophil Activation and Acute Lung Injury. COVID-19; abnormal lung humoral metabolism; drug; pulmonary edema; syndrome coronavirus 2; traditional Chinese medicine. 8 (5), 475481. Kiener M, Roldan N, Machahua C, Sengupta A, Geiser T, Guenat OT, Funke-Chambour M, Hobi N, Kruithof-de Julio M. Front Med (Lausanne). An Orally Active TRPV4 Channel Blocker Prevents and Resolves Pulmonary Edema Induced by Heart Failure. However, among all current treatments mentioned above, little attention has been paid to the abnormal humoral metabolism and pulmonary edema, which is a key factor threatening patients lives. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies. With the presence of active basolateral Na+-K+-ATPase, inhibition of the entry of apical Na+ can generate a concentration gradient inducing the uptake of basolateral Na+ with Cl by Na+-K+-2Cl cotransporter (NKCC) and thus induce the apical secretion of Cl (Solymosi et al., 2013). includes glycoproteins, membranes and nucleic acids. Natl. J. Respir. 4 When to. Decreased expression of alveolar Na-K-ATPase, dysregulation of sodium and potassium channels, aquaporins, and renin angiotensin system, and abnormal metabolism of bradykinin and hyaluronic acid as well as cytokine inflammatory storm all lead to ARDS and pulmonary edema. Diagn Pathol. Toxicol. doi:10.1038/s12276-018-0075-4, Zwaveling, S., Gerth van Wijk, R., and Karim, F. (2020). ACIP reviews data. There are multiple potential mechanisms leading to pulmonary edema in severe Coronavirus Disease (COVID-19) patients and understanding of those mechanisms may enable proper management of this condition. Pharmacol. We also obtain PFTs in recovering COVID-19 patients with severe pulmonary involvement or COVID-19-related ARDS, which applies to many patients who required hospitalization. doi:10.1056/NEJMoa013183, Sayegh, R., Auerbach, S. D., Li, X., Loftus, R. W., Husted, R. F., Stokes, J. Unable to load your collection due to an error, Unable to load your delegates due to an error. Br. TALLAHASSEE, Fla. Florida Surgeon General Joseph Ladapo personally altered a state-driven study about Covid-19 vaccines last year to suggest that some doses pose a . Ann. Effect and Mechanism of Astragaloside A on Acute Respiratory Failure in Rats. Copyright 2021 Cui, Chen, Zhou, Gong, Zhu, Lv, Guo, Duan, Zhou, Marcon and Ma. Elevated pulmonary venous pressure leads to faster fluid infiltration into the interstitial lung than the ability of the pulmonary lymphatic vessel to drain away fluid, resulting in pulmonary edema. (2016). The toad venom injection can significantly improve the pulmonary function of COVID-19 patients by regulating PaO2/FiO2 and ROX index and thus alleviate pulmonary edema. Angiotensin II Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors Usage Is Associated with Improved Inflammatory Status and Clinical Outcomes in COVID-19 Patients with Hypertension. Invited Review: Active Fluid Clearance from the Distal Air Spaces of the Lung. 274 (53), 3783437839. doi:10.1016/s0140-6736(20)30183-5, Hui, D. S. C., and Zumla, A.
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