DOI QR코드

DOI QR Code

의사에게 요구되는 인간이해를 통합한 질병발생모델의 제안

Human Understanding is Expected of the Physician: Proposing a Model of Disease Development

  • 박상흠 (순천향대학교 의과대학 순천향대학교 천안병원 소화기내과) ;
  • 박삼엘 (순천향대학교 의과대학 순천향대학교 천안병원 신장내과) ;
  • 김진영 (순천향대학교 의과대학 순천향대학교 천안병원 호흡기알레르기내과) ;
  • 이현아 (순천향대학교 의과대학 순천향대학교 천안병원 정신건강의학과) ;
  • 이상미 (순천향대학교 의과대학 순천향대학교 천안병원 핵의학과) ;
  • 이태훈 (순천향대학교 의과대학 순천향대학교 천안병원 소화기내과) ;
  • 배상병 (순천향대학교 의과대학 순천향대학교 천안병원 종양혈액내과) ;
  • 장성혜 (순천향대학교 의과대학 순천향대학교 천안병원 관절류마티스내과) ;
  • 장시형 (순천향대학교 의과대학 순천향대학교 천안병원 병리과) ;
  • 전성완 (순천향대학교 의과대학 순천향대학교 천안병원 내분비대사내과) ;
  • 문종호 (순천향대학교 의과대학 순천향대학교 부천병원 소화기내과)
  • Sang-Heum Park (Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicien) ;
  • Samel Park (Division of Nephrology, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicien) ;
  • Jin Young Kim (Division of Respiratory Allergy and Critical Care Medicine, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicien) ;
  • Hyeon Ah Lee (Department of Psychiatry, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicien) ;
  • Sang Mi Lee (Department of Nuclear Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicien) ;
  • Tae Hoon Lee (Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicien) ;
  • Sang Byung Bae (Division of Oncology and Hematology, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicien) ;
  • Sung Hae Chang (Division of Rheumatology, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicien) ;
  • Si Hyong Jang (Department of Pathology, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicien) ;
  • Sung Wan Chun (Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicien) ;
  • Jong Ho Moon (Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine)
  • 투고 : 2023.10.05
  • 심사 : 2023.11.22
  • 발행 : 2024.04.01

초록

In Harrison's Principles of Internal Medicine, human understanding is emphasized as one of three necessary characteristics that a physician must have. Inflammation, which is caused by inflammatory inducers (inf-ids), is a fundamental feature of disease at the cellular and molecular levels. Inflammation protects the body, but excessive or prolonged inflammation can be damaging and can cause disease. Humans are repeatedly exposed to external and internal environmental factors that generate inf-ids throughout their lives. External environmental factors include microbial and non-microbial inf-ids, as well as stressors that inevitably arise during social interactions. Internal environmental factors include the adaptive physiological response that is present from birth. Inf-ids may also be produced by the four-step habit loop, which consists of a cue (e.g., stressor), emotions, routine act (adaptive response), and a reward. Immune cells in the circulatory system and in tissues may have positive and negative effects in inflammatory responses. However, low-grade inflammation may be difficult to detect. We propose a model of disease development that integrates external and internal environmental factors from the perspective of human understanding.

키워드

과제정보

The authors would like to thank Shi Nae Yu, M.D., Division of Infectious Diseases, Department of Internal Medicine, Sae Hwan Lee, M.D., Division of Gastroenterology, Department of Internal Medicine, Young Sin Cho, M.D., Division of Gastroenterology, Department of Internal Medicine, and Jin Myoung Seok, M.D., Department of Neurology, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea, for recommending references.

참고문헌

  1. Nathan C, Ding A. Nonresolving inflammation. Cell 2010;140:871-882. https://doi.org/10.1016/j.cell.2010.02.029
  2. Medzhitov R. Inflammation 2010: new adventures of an old flame. Cell 2010;140:771-776. https://doi.org/10.1016/j.cell.2010.03.006
  3. Tian R, Hou G, Li D, Yuan TF. A possible change process of inflammatory cytokines in the prolonged chronic stress and its ultimate implications for health. ScientificWorldJournal 2014;2014:780616.
  4. Kumar V, Abbas AK, Aster JC. Inflammation and repair. In: Kumar V, Abbas AK, Aster JC, eds. Robbins & Cotran pathologic basis of disease. 10th ed. Philadelphia: Elsevier, 2021:71-113.
  5. Hotamisligil GS. Inflammation and metabolic disorders. Nature 2006;444:860-867.
  6. Aggarwal BB, Vijayalekshmi RV, Sung B. Targeting inflammatory pathways for prevention and therapy of cancer: short-term friend, long-term foe. Clin Cancer Res 2009;15:425-430. https://doi.org/10.1158/1078-0432.CCR-08-0149
  7. Loscalzo J, Fauci A, Kasper D, Hauser S, Longo D, Jameson JL. The practice of medicine. In: Loscalzo J, Fauci A, Kasper D, Hauser S, Longo D, Jameson JL, eds. Harrison's principles of internal medicine. 21st ed. Vol. 1. New York: McGraw-Hill, 2022:1-8.
  8. Fauci AS, Braunwald E, Isselbacher KJ, et al. The practice of medicine. In: Fauci AS, Braunwald E, Isselbacher KJ, et al., eds. Harrison's principles of internal medicine. 14th ed. Vol. 1. New York: McGraw Hill, 1998:1-6.
  9. Park SH, Song HR, Lee SW, Lee TH. Wouldn't human understanding be necessary to treat patients with pancreaticobiliary disease more effectively? Korean J Pancreas Biliary Tract 2018;23:89-100. https://doi.org/10.15279/kpba.2018.23.3.89
  10. Duhigg C. The power of habit: why we do what we do in life and business. New York: Penguin Random House, 2012.
  11. McEwen BS. Protective and damaging effects of stress mediators. N Engl J Med 1998;338:171-179. https://doi.org/10.1056/NEJM199801153380307
  12. Gonzalez-Diaz SN, Arias-Cruz A, Elizondo-Villarreal B, Monge-Ortega OP. Psychoneuroimmunoendocrinology: clinical implications. World Allergy Organ J 2017;10:19.
  13. Glaser R, Kiecolt-Glaser JK. Stress-induced immune dysfunction: implications for health. Nat Rev Immunol 2005;5:243-251. https://doi.org/10.1038/nri1571
  14. Clear J. Atomic habits: an easy & proven way to build good habits & break bad ones. New York: Avery Publishing Group, 2018.
  15. Kotas ME, Medzhitov R. Homeostasis, inflammation, and disease susceptibility. Cell 2015;160:816-827. https://doi.org/10.1016/j.cell.2015.02.010
  16. Rohleder N. Stimulation of systemic low-grade inflammation by psychosocial stress. Psychosom Med 2014;76:181-189. https://doi.org/10.1097/PSY.0000000000000049
  17. Marx J. Cancer research. Inflammation and cancer: the link grows stronger. Science 2004;306:966-968. https://doi.org/10.1126/science.306.5698.966
  18. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005;352:1685-1895. https://doi.org/10.1056/NEJMra043430
  19. Medzhitov R. Origin and physiological roles of inflammation. Nature 2008;454:428-435. https://doi.org/10.1038/nature07201
  20. McCusker K. Mechanisms of respiratory tissue injury from cigarette smoking. Am J Med 1992;93:18S-21S. https://doi.org/10.1016/0002-9343(92)90622-I
  21. Pope CA 3rd, Ezzati M, Dockery DW. Fine-particulate air pollution and life expectancy in the United States. N Engl J Med 2009;360:376-386. https://doi.org/10.1056/NEJMsa0805646
  22. Steenland K, Stayner L. Silica, asbestos, man-made mineral fibers, and cancer. Cancer Causes Control 1997;8:491-503. https://doi.org/10.1023/A:1018469607938
  23. Fujiki H. Gist of Dr. Katsusaburo Yamagiwa's papers entitled "Experimental study on the pathogenesis of epithelial tumors" (I to VI reports). Cancer Sci 2014;105:143-149. https://doi.org/10.1111/cas.12333
  24. Seok SJ, Gil HW, Jeong DS, Yang JO, Lee EY, Hong SY. Paraquat intoxication in subjects who attempt suicide: why they chose paraquat. Korean J Intern Med 2009;24:247-251. https://doi.org/10.3904/kjim.2009.24.3.247
  25. Steenland K, Fletcher T, Savitz DA. Epidemiologic evidence on the health effects of perfluorooctanoic acid (PFOA). Environ Health Perspect 2010;118:1100-1108. https://doi.org/10.1289/ehp.0901827
  26. Hoffman RS, Burns MM, Gosselin S. Ingestion of caustic substances. N Engl J Med 2020;382:1739-1748. https://doi.org/10.1056/NEJMra1810769
  27. Kang HK, Dalager NA, Needham LL, et al. Health status of Army Chemical Corps Vietnam veterans who sprayed defoliant in Vietnam. Am J Ind Med 2006;49:875-884. https://doi.org/10.1002/ajim.20385
  28. Marfella R, Prattichizzo F, Sardu C, et al. Microplastics and nanoplastics in atheromas and cardiovascular events. N Engl J Med 2024;390:900-910. https://doi.org/10.1056/NEJMoa2309822
  29. de Vries MA, Klop B, Janssen HW, Njo TL, Westerman EM, Cabezas MC. Postprandial inflammation: targeting glucose and lipids. Adv Exp Med Biol 2014;824:161-170. https://doi.org/10.1007/978-3-319-07320-0_12
  30. Perez-Ruiz F, Castillo E, Chinchilla SP, Herrero-Beites AM. Clinical manifestations and diagnosis of gout. Rheum Dis Clin North Am 2014;40:193-206. https://doi.org/10.1016/j.rdc.2014.01.003
  31. Gao B, Bataller R. Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology 2011;141:1572-1585. https://doi.org/10.1053/j.gastro.2011.09.002
  32. Dunn W, Shah VH. Pathogenesis of alcoholic liver disease. Clin Liver Dis 2016;20:445-456. https://doi.org/10.1016/j.cld.2016.02.004
  33. Erridge C, Attina T, Spickett CM, Webb DJ. A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation. Am J Clin Nutr 2007;86:1286-1292. https://doi.org/10.1093/ajcn/86.5.1286
  34. Ghanim H, Abuaysheh S, Sia CL, et al. Increase in plasma endotoxin concentrations and the expression of Toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal: implications for insulin resistance. Diabetes Care 2009;32:2281-2287. https://doi.org/10.2337/dc09-0979
  35. Laugerette F, Vors C, Geloen A, et al. Emulsified lipids increase endotoxemia: possible role in early postprandial low-grade inflammation. J Nutr Biochem 2011;22:53-59. https://doi.org/10.1016/j.jnutbio.2009.11.011
  36. Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Annu Rev Immunol 2011;29:415-445. https://doi.org/10.1146/annurev-immunol-031210-101322
  37. Drake I, Sonestedt E, Ericson U, Wallstrom P, Orho-Melander M. A Western dietary pattern is prospectively associated with cardio-metabolic traits and incidence of the metabolic syndrome. Br J Nutr 2018;119:1168-1176. https://doi.org/10.1017/S000711451800079X
  38. Balistreri CR, Caruso C, Candore G. The role of adipose tissue and adipokines in obesity-related inflammatory diseases. Mediators Inflamm 2010;2010:802078.
  39. Schelbert KB. Comorbidities of obesity. Prim Care 2009;36:271-285. https://doi.org/10.1016/j.pop.2009.01.009
  40. Pavlov VA, Tracey KJ. The vagus nerve and the inflammatory reflex--linking immunity and metabolism. Nat Rev Endocrinol 2012;8:743-754. https://doi.org/10.1038/nrendo.2012.189
  41. Chrousos GP. The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N Engl J Med 1995;332:1351-1362. https://doi.org/10.1056/NEJM199505183322008
  42. Reiche EM, Nunes SO, Morimoto HK. Stress, depression, the immune system, and cancer. Lancet Oncol 2004;5:617-625. https://doi.org/10.1016/S1470-2045(04)01597-9
  43. Downing JE, Miyan JA. Neural immunoregulation: emerging roles for nerves in immune homeostasis and disease. Immunol Today 2000;21:281-289.
  44. Black PH. The inflammatory response is an integral part of the stress response: implications for atherosclerosis, insulin resistance, type II diabetes and metabolic syndrome X. Brain Behav Immun 2003;17:350-364. https://doi.org/10.1016/S0889-1591(03)00048-5
  45. Oberbeck R. Catecholamines: physiological immunomodulators during health and illness. Curr Med Chem 2006;13:1979-1989. https://doi.org/10.2174/092986706777584997
  46. Chen GY, Nunez G. Sterile inflammation: sensing and reacting to damage. Nat Rev Immunol 2010;10:826-837. https://doi.org/10.1038/nri2873
  47. Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 2009;30:1073-1081. https://doi.org/10.1093/carcin/bgp127
  48. Coussens LM, Werb Z. Inflammation and cancer. Nature 2002;420:860-867.
  49. Arneth B. Tumor microenvironment. Medicina (Kaunas) 2019;56:15.
  50. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008;454:436-444. https://doi.org/10.1038/nature07205
  51. Greten FR, Grivennikov SI. Inflammation and cancer: triggers, mechanisms, and consequences. Immunity 2019;51:27-41. https://doi.org/10.1016/j.immuni.2019.06.025
  52. de Freitas Saito R, Rangel MC, Chandler M, Beasock D, Afonin KA, Chammas R. Cancer therapy-induced inflammation and its consequences. In: de Araujo DR, Carneiro-Ramos M, eds. Biotechnology applied to inflammatory diseases: cellular mechanisms and nanomedicine. Berlin: Springer, 2023:49-75.
  53. Hall JE, Hall ME. Guyton and Hall textbook of medical physiology. 14th ed. Amsterdam: Elsevier, 2020.
  54. Barbera M, Fitzgerald RC. Cellular mechanisms of Barrett's esophagus development. Surg Oncol Clin N Am 2009;18:393-410. https://doi.org/10.1016/j.soc.2009.03.001
  55. Vaezi MF, Richter JE. Role of acid and duodenogastroesophageal reflux in gastroesophageal reflux disease. Gastroenterology 1996;111:1192-1199. https://doi.org/10.1053/gast.1996.v111.pm8898632
  56. Kamisawa T, Takuma K, Anjiki H, et al. Pancreaticobiliary maljunction. Clin Gastroenterol Hepatol 2009;7 Suppl 11:S84-S88. https://doi.org/10.1016/j.cgh.2009.08.024
  57. Langell JT, Mulvihill SJ. Gastrointestinal perforation and the acute abdomen. Med Clin North Am 2008;92:599-625, viii-ix. https://doi.org/10.1016/j.mcna.2007.12.004
  58. Soreide K, Thorsen K, Harrison EM, et al. Perforated peptic ulcer. Lancet 2015;386:1288-1298. https://doi.org/10.1016/S0140-6736(15)00276-7
  59. Sherman S, Lehman GA. Sphincter of Oddi dysfunction: diagnosis and treatment. JOP 2001;2:382-400.
  60. Brites D. The evolving landscape of neurotoxicity by unconjugated bilirubin: role of glial cells and inflammation. Front Pharmacol 2012;3:88.
  61. Pavlidis ET, Pavlidis TE. Pathophysiological consequences of obstructive jaundice and perioperative management. Hepatobiliary Pancreat Dis Int 2018;17:17-21. https://doi.org/10.1016/j.hbpd.2018.01.008
  62. Guarnieri G, Biolo G, Zanetti M, Barazzoni R. Chronic systemic inflammation in uremia: potential therapeutic approaches. Semin Nephrol 2004;24:441-445. https://doi.org/10.1016/j.semnephrol.2004.06.007
  63. Cantarin MPM, Whitaker-Menezes D, Lin Z, Falkner B. Uremia induces adipose tissue inflammation and muscle mitochondrial dysfunction. Nephrol Dial Transplant 2017;32:943-951. https://doi.org/10.1093/ndt/gfx050
  64. Franceschi C, Capri M, Monti D, et al. Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 2007;128:92-105. https://doi.org/10.1016/j.mad.2006.11.016
  65. Goldman L. Too much of a good thing: how four key survival traits are now killing us. New York: Little, Brown Spark, 2015.
  66. Kim YK, Maes M. The role of the cytokine network in psychological stress. Acta Neuropsychiatr 2003;15:148-155. https://doi.org/10.1034/j.1601-5215.2003.00026.x
  67. Sorrells SF, Caso JR, Munhoz CD, Sapolsky RM. The stressed CNS: when glucocorticoids aggravate inflammation. Neuron 2009;64:33-39. https://doi.org/10.1016/j.neuron.2009.09.032
  68. Maniam J, Morris MJ. The link between stress and feeding behaviour. Neuropharmacology 2012;63:97-110. https://doi.org/10.1016/j.neuropharm.2012.04.017
  69. Simonton OC, Creighton J, Simonton SM, Matthews S, Creighton JL. Getting well again: the bestselling classic about the Simontons' revolutionary lifesaving self-awareness techniques. New York: Bantam Books, 1992.
  70. Cannon WB. The emergency function of the adrenal medulla in pain and the major emotions. Am J Physiol 1914;33:356-372. https://doi.org/10.1152/ajplegacy.1914.33.2.356
  71. Varki A. Nothing in medicine makes sense, except in the light of evolution. J Mol Med (Berl) 2012;90:481-494. https://doi.org/10.1007/s00109-012-0900-5
  72. Segerstrom SC, Miller GE. Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychol Bull 2004;130:601-630. https://doi.org/10.1037/0033-2909.130.4.601
  73. Mawdsley JE, Rampton DS. Psychological stress in IBD: new insights into pathogenic and therapeutic implications. Gut 2005;54:1481-1491. https://doi.org/10.1136/gut.2005.064261
  74. Holmes TH, Rahe RH. The social readjustment rating scale. J Psychosom Res 1967;11:213-218. https://doi.org/10.1016/0022-3999(67)90010-4
  75. Szabo S, Tache Y, Somogyi A. The legacy of Hans Selye and the origins of stress research: a retrospective 75 years after his landmark brief "letter" to the editor#  of Nature. Stress 2012;15:472-478. https://doi.org/10.3109/10253890.2012.710919
  76. Ekman P. Emotions revealed: recognizing faces and feelings to improve communication and emotional life. 2nd ed. New York: St. Martin's Press, 2007.
  77. Zeelenberg M, Nelissen RMA, Breugelmans SM, Pieters R. On emotion specificity in decision making: why feeling is for doing. Judgm Decis Mak 2008;3:18-27. https://doi.org/10.1017/S1930297500000139
  78. Phelps EA, Lempert KM, Sokol-Hessner P. Emotion and decision making: multiple modulatory neural circuits. Annu Rev Neurosci 2014;37:263-287. https://doi.org/10.1146/annurev-neuro-071013-014119
  79. Lerner JS, Li Y, Valdesolo P, Kassam KS. Emotion and decision making. Annu Rev Psychol 2015;66:799-823. https://doi.org/10.1146/annurev-psych-010213-115043
  80. Ulrich-Lai YM, Fulton S, Wilson M, Petrovich G, Rinaman L. Stress exposure, food intake and emotional state. Stress 2015;18:381-399.
  81. Macht M. How emotions affect eating: a five-way model. Appetite 2008;50:1-11. https://doi.org/10.1016/j.appet.2007.07.002
  82. Evers C, Dingemans A, Junghans AF, Boeve A. Feeling bad or feeling good, does emotion affect your consumption of food? A meta-analysis of the experimental evidence. Neurosci Biobehav Rev 2018;92:195-208. https://doi.org/10.1016/j.neubiorev.2018.05.028
  83. Pereira-Miranda E, Costa PRF, Queiroz VAO, Pereira-Santos M, Santana MLP. Overweight and obesity associated with higher depression prevalence in adults: a systematic review and meta-analysis. J Am Coll Nutr 2017;36:223-233. https://doi.org/10.1080/07315724.2016.1261053
  84. Wills TA. Stress and coping in early adolescence: relationships to substance use in urban school samples. Health Psychol 1986;5:503-529. https://doi.org/10.1037/0278-6133.5.6.503
  85. Leventhal H, Cleary PD. The smoking problem: a review of the research and theory in behavioral risk modification. Psychol Bull 1980;88:370-405. https://doi.org/10.1037/0033-2909.88.2.370
  86. Russell JA, Mehrabian A. The mediating role of emotions in alcohol use. J Stud Alcohol 1975;36:1508-1536. https://doi.org/10.15288/jsa.1975.36.1508
  87. Lasser K, Boyd JW, Woolhandler S, Himmelstein DU, McCormick D, Bor DH. Smoking and mental illness: a population-based prevalence study. JAMA 2000;284:2606-2610. https://doi.org/10.1001/jama.284.20.2606
  88. Sayette MA. The effects of alcohol on emotion in social drinkers. Behav Res Ther 2017;88:76-89. https://doi.org/10.1016/j.brat.2016.06.005
  89. Black PH, Garbutt LD. Stress, inflammation and cardiovascular disease. J Psychosom Res 2002;52:1-23. https://doi.org/10.1016/S0022-3999(01)00302-6
  90. Szalay J. What is inflammation [Internet]. New York (NY): Live Science, c2018 [cited 2018 Oct 19]. Available from: http://www.livescience.com/52344-inflammation.html.
  91. Harris NB. The deepest well: healing the long-term effects of childhood adversity. Boston: Houghton Mifflin Harcourt, 2018.
  92. Schulkin J, McEwen BS, Gold PW. Allostasis, amygdala, and anticipatory angst. Neurosci Biobehav Rev 1994;18:385-396. https://doi.org/10.1016/0149-7634(94)90051-5
  93. Schulz P, Kirschbaum C, Prussner J, Hellhammer D. Increased free cortisol secretion after awakening in chronically stressed individuals due to work overload. Stress Med 1998;14:91-97. https://doi.org/10.1002/(SICI)1099-1700(199804)14:2<91::AID-SMI765>3.0.CO;2-S
  94. Gantt WH. Principles of nervous breakdown-schizokinesis and autokinesis. Ann N Y Acad Sci 1953;56:143-163. https://doi.org/10.1111/j.1749-6632.1953.tb30213.x
  95. Kandel ER. In search of memory: the emergence of a new science of mind. 1st ed. New York: W. W. Norton & Company, 2007.
  96. Lown B. The lost art of healing: practicing compassion in medicine. New York: Ballantine Books, 1999.
  97. Pavlov PI. Conditioned reflexes: an investigation of the physiological activity of the cerebral cortex. Ann Neurosci 2010;17:136-141. https://doi.org/10.5214/ans.0972-7531.1017309
  98. Chaplin TM, Niehaus C, Goncalves SF. Stress reactivity and the developmental psychopathology of adolescent substance use. Neurobiol Stress 2018;9:133-139. https://doi.org/10.1016/j.ynstr.2018.09.002
  99. Felitti VJ, Anda RF, Nordenberg D, et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The adverse childhood experiences (ACE) study. Am J Prev Med 1998;14:245-258. https://doi.org/10.1016/S0749-3797(98)00017-8
  100. National Scientific Council. Excessive stress disrupts the development of brain architecture. J Child Serv 2014;9:143-153. https://doi.org/10.1108/JCS-01-2014-0006
  101. Teicher MH, Samson JA. Annual research review: enduring neurobiological effects of childhood abuse and neglect. J Child Psychol Psychiatry 2016;57:241-266. https://doi.org/10.1111/jcpp.12507
  102. Koss KJ, Gunnar MR. Annual research review: early adversity, the hypothalamic-pituitary-adrenocortical axis, and child psychopathology. J Child Psychol Psychiatry 2018;59:327-346. https://doi.org/10.1111/jcpp.12784
  103. Grasso DJ, Ford JD, Briggs-Gowan MJ. Early life trauma exposure and stress sensitivity in young children. J Pediatr Psychol 2013;38:94-103. https://doi.org/10.1093/jpepsy/jss101
  104. Danese A, Lewis SJ. Psychoneuroimmunology of early-life stress: the hidden wounds of childhood trauma? Neuropsychopharmacology 2017;42:99-114. https://doi.org/10.1038/npp.2016.198
  105. Schwandt ML, Heilig M, Hommer DW, George DT, Ramchandani VA. Childhood trauma exposure and alcohol dependence severity in adulthood: mediation by emotional abuse severity and neuroticism. Alcohol Clin Exp Res 2013;37:984-992. https://doi.org/10.1111/acer.12053
  106. Ekman P. Are there basic emotions? Psychol Rev 1992;99:550-553. https://doi.org/10.1037/0033-295X.99.3.550
  107. Chrousos GP, Gold PW. The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. JAMA 1992;267:1244-1252. https://doi.org/10.1001/jama.1992.03480090092034
  108. Wright HL, Moots RJ, Bucknall RC, Edwards SW. Neutrophil function in inflammation and inflammatory diseases. Rheumatology (Oxford) 2010;49:1618-1631. https://doi.org/10.1093/rheumatology/keq045
  109. Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest 2012;122:787-795. https://doi.org/10.1172/JCI59643
  110. Bromberg-Martin ES, Matsumoto M, Hikosaka O. Dopamine in motivational control: rewarding, aversive, and alerting. Neuron 2010;68:815-834. https://doi.org/10.1016/j.neuron.2010.11.022
  111. Tracey KJ. The inflammatory reflex. Nature 2002;420:853-859. https://doi.org/10.1038/nature01321
  112. Andersson U, Tracey KJ. Neural reflexes in inflammation and immunity. J Exp Med 2012;209:1057-1068. https://doi.org/10.1084/jem.20120571
  113. Bruunsgaard H, Pedersen BK. Age-related inflammatory cytokines and disease. Immunol Allergy Clin North Am 2003;23: 15-39. https://doi.org/10.1016/S0889-8561(02)00056-5
  114. Tkacova R. Systemic inflammation in chronic obstructive pulmonary disease: may adipose tissue play a role? Review of the literature and future perspectives. Mediators Inflamm 2010;2010:585989.
  115. Dinh QN, Drummond GR, Sobey CG, Chrissobolis S. Roles of inflammation, oxidative stress, and vascular dysfunction in hypertension. Biomed Res Int 2014;2014:406960.
  116. Danesh J. Smoldering arteries? Low-grade inflammation and coronary heart disease. JAMA 1999;282:2169-2171. https://doi.org/10.1001/jama.282.22.2169
  117. Siti HN, Kamisah Y, Kamsiah J. The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review). Vascul Pharmacol 2015;71:40-56. https://doi.org/10.1016/j.vph.2015.03.005
  118. Danesh J, Whincup P, Walker M, et al. Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses. BMJ 2000;321:199-204. https://doi.org/10.1136/bmj.321.7255.199
  119. Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 2001;286:327-334. https://doi.org/10.1001/jama.286.3.327
  120. Duncan BB, Schmidt MI, Pankow JS, et al. Low-grade systemic inflammation and the development of type 2 diabetes: the atherosclerosis risk in communities study. Diabetes 2003; 52:1799-1805. https://doi.org/10.2337/diabetes.52.7.1799
  121. Fuentes E, Fuentes F, Vilahur G, Badimon L, Palomo I. Mechanisms of chronic state of inflammation as mediators that link obese adipose tissue and metabolic syndrome. Mediators Inflamm 2013;2013:136584.
  122. Catrysse L, van Loo G. Inflammation and the metabolic syndrome: the tissue-specific functions of NF-κB. Trends Cell Biol 2017;27:417-429. https://doi.org/10.1016/j.tcb.2017.01.006
  123. Tajti G, Gesztelyi R, Pak K, et al. Positive correlation of airway resistance and serum asymmetric dimethylarginine level in COPD patients with systemic markers of low-grade inflammation. Int J Chron Obstruct Pulmon Dis 2017;12:873-884. https://doi.org/10.2147/COPD.S127373
  124. Robinson WH, Lepus CM, Wang Q, et al. Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis. Nat Rev Rheumatol 2016;12:580-592. https://doi.org/10.1038/nrrheum.2016.136
  125. von Kanel R, Hepp U, Kraemer B, et al. Evidence for low-grade systemic proinflammatory activity in patients with posttraumatic stress disorder. J Psychiatr Res 2007;41:744-752. https://doi.org/10.1016/j.jpsychires.2006.06.009
  126. Speer K, Upton D, Semple S, McKune A. Systemic low-grade inflammation in post-traumatic stress disorder: a systematic review. J Inflamm Res 2018;11:111-121. https://doi.org/10.2147/JIR.S155903
  127. Dowlati Y, Herrmann N, Swardfager W, et al. A meta-analysis of cytokines in major depression. Biol Psychiatry 2010;67:446-457. https://doi.org/10.1016/j.biopsych.2009.09.033
  128. Felger JC, Lotrich FE. Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications. Neuroscience 2013;246:199-229. https://doi.org/10.1016/j.neuroscience.2013.04.060
  129. Ronnback C, Hansson E. The importance and control of low-grade inflammation due to damage of cellular barrier systems that may lead to systemic inflammation. Front Neurol 2019;10:533.
  130. Miwa H, Oshima T, Tomita T, et al. Recent understanding of the pathophysiology of functional dyspepsia: role of the duodenum as the pathogenic center. J Gastroenterol 2019;54:305-311. https://doi.org/10.1007/s00535-019-01550-4
  131. Lubbers ER, Price MV, Mohler PJ. Arrhythmogenic substrates for atrial fibrillation in obesity. Front Physiol 2018;9:1482.
  132. Van't Klooster CC, Ridker PM, Hjortnaes J, et al. The relation between systemic inflammation and incident cancer in patients with stable cardiovascular disease: a cohort study. Eur Heart J 2019;40:3901-3909. https://doi.org/10.1093/eurheartj/ehz587
  133. Ahechu P, Zozaya G, Marti P, et al. NLRP3 inflammasome: a possible link between obesity-associated low-grade chronic inflammation and colorectal cancer development. Front Immunol 2018;9:2918.
  134. Schuckit MA. Alcohol, anxiety, and depressive disorders. Alcohol Health Res World 1996;20:81-85.
  135. Lu Y, Jin X, Feng LW, Tang C, Neo M, Ho RC. Effects of illness perception on negative emotions and fatigue in chronic rheumatic diseases: rumination as a possible mediator. World J Clin Cases 2022;10:12515-12531. https://doi.org/10.12998/wjcc.v10.i34.12515
  136. Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm Rep 2021;70:1-187. https://doi.org/10.15585/mmwr.rr7004a1
  137. Derbyshire KL, Grant JE. Compulsive sexual behavior: a review of the literature. J Behav Addict 2015;4:37-43. https://doi.org/10.1556/2006.4.2015.003
  138. Marks LR, Nolan NS, Liang SY, Durkin MJ, Weimer MB. Infectious complications of injection drug use. Med Clin North Am 2022;106:187-200. https://doi.org/10.1016/j.mcna.2021.08.006
  139. Mirin SM, Meyer RE, McNamee HB. Psychopathology and mood during heroin use: acute vs chronic effects. Arch Gen Psychiatry 1976;33:1503-1508. https://doi.org/10.1001/archpsyc.1976.01770120107011
  140. Tomaka J, Blascovich J, Kibler J, Ernst JM. Cognitive and physiological antecedents of threat and challenge appraisal. J Pers Soc Psychol 1997;73:63-72. https://doi.org/10.1037/0022-3514.73.1.63
  141. Blackburn EH, Epel ES, Lin J. Human telomere biology: a contributory and interactive factor in aging, disease risks, and protection. Science 2015;350:1193-1198. https://doi.org/10.1126/science.aab3389
  142. Wolfe RR. The underappreciated role of muscle in health and disease. Am J Clin Nutr 2006;84:475-482. https://doi.org/10.1093/ajcn/84.3.475
  143. Lacey J, Corbett J, Forni L, et al. A multidisciplinary consensus on dehydration: definitions, diagnostic methods and clinical implications. Ann Med 2019;51:232-251. https://doi.org/10.1080/07853890.2019.1628352
  144. Johnson KVA. Gut microbiome composition and diversity are related to human personality traits. Hum Microb J 2020;15:100069.
  145. Sinha R. Chronic stress, drug use, and vulnerability to addiction. Ann N Y Acad Sci 2008;1141:105-130. https://doi.org/10.1196/annals.1441.030
  146. Anand P, Kunnumakkara AB, Sundaram C, et al. Cancer is a preventable disease that requires major lifestyle changes. Pharm Res 2008;25:2097-2116. https://doi.org/10.1007/s11095-008-9661-9
  147. Blackburn E, Epel E. The telomere effect: a revolutionary approach to living younger, healthier, longer. New York: Grand Central Publishing, 2017.
  148. Sproston NR, Ashworth JJ. Role of C-reactive protein at sites of inflammation and infection. Front Immunol 2018;9:754.
  149. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000;342:836-843. https://doi.org/10.1056/NEJM200003233421202