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Role of epigenetic abnormalities and intervention in obstructive sleep apnea target organs

Chinese Medical Journal 2023年第6期136卷 631-644页

作者： Yanru Ou Dandan Zong Ruoyun Ouyang Department of Pulmonary and Critical Care Medicine The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China Research Unit of Respiratory Disease Central South UniversityChangshaHunan 410011China Diagnosis and Treatment Center of Respiratory Disease Central South UniversityChangshaHunan 410011China

Obstructive sleep apnea(OSA)is a common condition that has considerable impacts on human health.Epigenetics has become a rapidly developing and exciting area in biology,and it is defined as heritable alterations in gene expression and has regulatory effects on disease progression.However,the published literature that is integrating both of them is not sufficient.The purpose of this article is to explore the relationship between OSA and epigenetics and to offer better diagnostic methods and treatment options.Epigenetic modifications mainly manifest as post-translational modifications in DNA and histone proteins and regulation of non-coding RNAs.Chronic intermittent hypoxia-mediated epigenetic alterations are involved in the progression of OSA and diverse multiorgan injuries,including cardiovascular disease,metabolic disorders,pulmonary hypertension,neural dysfunction,and even tumors.This article provides deeper insights into the disease mechanism of OSA and potential applications of targeted diagnosis,treatment,and prognosis in OSA complications.

关键词： Complications Epigenetics Intermittent hypoxia multiorgan Obstructive sleep apnea

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multiorgan chronic inflammatory hepatobiliary pancreatic murine model deficient in tumor necrosis factor receptors 1 and 2

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World Journal of Gastroenterology 2016年第21期22卷 4988-4998页

作者： Helieh S Oz Department of Physiology and Internal Medicine College of Medicine University of Kentucky Medical Center

AIM: To provoke persistent/chronic multiorgan inflammatory response and to contribute to stones formation followed by fibrosis in hepatobiliary and pancreatic tissues. METHODS: Tumor necrosis factor receptors 1 and 2(TNFR1/R2) deficient mice reared in-house were given dibutyltin dichloride(DBTC) twice within 10 d by oral gavage delivery. Sham control animals received vehicle treatment and na?ve animals remained untreated throughout the study. Animals were monitored daily for symptoms of pain and discomfort. The abdominal and hindpaw hypersensitivity were assessed with von Frey microfilaments. Exploratory behaviors were recorded at the baseline, after initiation of treatment, and before study termination. Histopathological changes were examined postmortem in tissues. Collagen accumulation and fibrosis were confirmed with Sirius Red staining. RESULTS: Animals lost weight after oral administration of DBTC and developed persistent inflammatory abdominal and hindpaw hypersensitivity compared to sham-treated controls(P < 0.0001). These pain related secondary mechanical hypersensitivity responses increased more than 2-fold in DBTC-treated animals. The drastically diminished rearing and grooming rates persisted after DBTC administration throughout the study. Gross as well as micropathology at one month confirmed that animals treated with DBTC developed chronic hepatobiliary injuries evidenced with activation of stellate cells, multifocal necrosis, fatty degeneration of hepatocytes, periportal infiltration of inflammatory cells, and prominent biliary ductal dilation. The severity of hepatitis was scored 3.7 ± 0.2(severe) in DBTC-treated animals vs score 0(normal) in shamtreated animals. Fibrotic thickening was extensive around portal ducts, in hepatic parenchyma as well as in lobular pancreatic structures and confirmed with Sirius Red histopathology. In addition, pancreatic microarchitecture was presented with distortion of islets, and parenchyma, infiltration of inflammatory cells, degeneration, vacuolization, and necros

关键词： Inflammatory pain multiorgan Hepatitis Pancreatitis Calculi formation Gall bladder Hepatobiliary inf

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Therapeutic plasma exchange and continuous renal replacement therapy for severe hyperthyroidism and multi-organ failure:A case report

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World Journal of Clinical Cases 2019年第4期7卷 500-507页

作者： Jun-Hui Ba Ben-Quan Wu Yan-Hong Wang Yun-Feng Shi Department of Medical Intensive Unit the Third Affiliated Hospital of Sun Yat-Sen University

BACKGROUND Severe hyperthyroidism is a life-threatening exacerbation of thyrotoxicosis,characterized by high fever and multiorgan failure. The most common medical treatments are administration of antithyroid drugs and radioactive iodine, and thyroidectomy. In some patients, antithyroid therapy is limited due to serious adverse effects or failure to control disease progression. In some extreme cases,such as thyroid storm, conventional therapy alone does not yield effective and rapid improvement before the development of multiorgan failure.CASE SUMMARY This report describes a Chinese patient with severe hyperthyroidism accompanied by multiorgan failure, who was transferred to the medical intensive care unit of our hospital. The patient presented with palpitations, vomiting,diarrhea, and shortness of breath for a week. Laboratory tests showed elevation of thyroid hormones. Hepatic failure occurred with high aminotransferase levels and jaundice. Given her abnormal liver function and medication history, we could not exclude diagnosis of propylthiouracil-induced hepatic failure.Moreover, she also suffered from heart failure. Therapeutic plasma exchange(commonly known as TPE) and continuous renal replacement therapy(commonly known as CRRT) were used as life-saving therapy, which resulted in notable improvement of clinical symptoms and laboratory tests.CONCLUSION Combined TPE and CRRT are safe and effective for patients with hyperthyroidism and multiorgan failure.

关键词： Severe hyperthyroidism Propylthiouracil-induced hepatotoxicity multiorgan

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Multiple Organ Dysfunction Syndrome (MODS): Is It Preventable or Inevitable?

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International Journal of Clinical Medicine 2012年第7期3卷 722-730页

作者： Ayman El-Menyar Hassan Al Thani El Rasheid Zakaria Ahmad Zarour Mazin Tuma Husham AbdulRahman Ashok Parchani Ruben Peralta Rifat Latifi Clinical Medicine Weill Cornell Medical School Doha Qatar Medical Research Center Hamad Medical Corporation (HMC) Doha Qatar The Clinical Research Trauma Surgery Hamad Medical Corporation (HMC) Doha Qatar Trauma surgery Hamad Medical Corporation (HMC) Doha Qatar

Multiple organ dysfunction syndrome (MODS) is a systemic, dysfunctional inflammatory response that requires long intensive care unit (ICU) stay. It is characterized with high mortality rate depending on the number of organs involved. It has been recognized that organ failure does not occur as an all-or-none rule, but rather a range of organ dysfunction exists resulting in clinical organ failure. In the absence of a gold standard scoring or tool for early diagnosis or prediction of MODS, a novel bio-clinical scoring is mandatory. Moreover, understanding the pathophysiology of MODS in medical, surgical and trauma, ICUs should take a priority to achieve a favorable outcome. Herein we reviewed the literatures published in English language through the research engines (MEDLINE, Scopus, and EBASE) from 1982 to 2011 using key words: “multiorgan dysfunction”, “organ failure”, “intensive care units” to highlight the definition, mechanism, diagnosis and prediction of MODS particularly at its earliest stages. Bring up new bio-clinical scoring to a stage where it is ready for field trials will pave the way for implementing new risk-stratification strategy in the intensive care to reduce the morbidity and mortality and save resources. Prospective studies are needed to answer our question and to shift MODS from an inevitable to a preventable disorder.

关键词： multiorgan Dysfunction Failure Intensive Care Units

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