The Mechanism of Extracellular Vesicles Containing Mitochondrial DNA in ARDS Lung Injury Caused by Extrapulmonary Sepsis

Study Overview
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Brief Summary
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The acute respiratory distress syndrome (ARDS) remains a common and morbid complication of critical illness. Sepsis contribute to a lot of ARDS cases, but mechanisms by which non-pulmonary insults such as extrapulmonary sepsis propagate lung injury remain unclear. Most eukaryotic cells release small anuclear membrane-bound vesicles into the extracellular environment in either physiological or pathophysiological conditions, often called extracellular vesicles (EVs) .Through their cargo containing bioactive molecules such as proteins, mRNAs, and microRNAs and their interaction with target cells, EVs are recognized as important mediators of cellular communication. Mitochondrial contents are clearly present in EVs, and mitochondrial cargo within EVs have been shown to stimulate the production of proinﬂammatory cytokines, further enhancing LPS-induced inﬂammation. Among the mitochondrial contents, mtDNA was present at higher levels in EVs.Therefore, we hypothesis, EVs containing mtDNA play an important role in the occurrence and development of ARDS caused by extrapulmonary sepsis.

Detailed Description
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Inclusion criteria: Patients with ARDS caused by abdominal infection Exclusion criteria: age <18 years old or pregnancy; death or discharge within 24 hours after admission; advanced tumor The pathological information of the patients was collected on 24h, 48h after admission including demographic data, Acute Physiology and Chronic Health Evaluation (APACHE) II score , number of organ failures included in the Sequential Organ Failure Assessment (SOFA) score. The levels of lactate and inflammatory mediators (i.e., plasma C-reactive protein and procalcitonin) were detected on 24h and 48h after admission. All patients were followed up for 28 days, and all-cause mortality was recorded. The durations of mechanical ventilation and ICU stay were also recorded. The primary outcome was mortality on Day 28. Secondary outcomes included the ventilator days and ICU length of stay. Peripheral blood samples (2 mL) were collected on 24h and 48h after admission to the ICU. EVs were isolated from the plasma, and mtDNA concentration of plasma DNA was evaluated by RT-qPCR.

Official Title
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The Mechanism of Extracellular Vesicles Containing Mitochondrial DNA in ARDS Lung Injury Caused by Extrapulmonary Sepsis

Conditions
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ARDS, Human

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with ARDS caused by abdominal infection Exclusion Criteria: age <18 years old or pregnancy; death or discharge within 24 hours after admission; advanced tumor

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28-day mortality |  | All patients were followed up for 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilator days |  | All patients were followed up for 28 days | 
| ICU stay |  | All patients were followed up for 28 days |