Role and Molecular Mechanism of Farnesoid X Receptor(FXR) and RIPK3 in the Formation of Acute Respiratory Distress Syndrome in Neonates

Study Overview
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Brief Summary
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In the clinical data, the changes of RIPK3 and FXR were monitored in the lung lavage fluid and blood from the patients. In vivo experiments to find high risk factors to induce AEC necrosis and further lead to ARDS evidence, can provide a more direct theoretical research foundation for the pathogenesis of ARDS.

Detailed Description
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Divided into 3 Arms ALI :Diagnostic criteria: 1.Acute onset；2.FiO2/ PaO2< 40.0 kPa (300mmHg, ALI); 3.Chest X-ray showed that the double lung texture increased, the increase of crude, fuzzy, visible diffuse patchy infiltration shadow with compensatory emphysema, for the most early performance; B. double lung field large sheet, asymmetric, edge fuzzy infiltration shadow, the most dense in the lung；4. Echocardiography, left atrial hypertension; 5.The gestational age >35 week, have maternal age cholestasis (severe), sepsis or meconium aspiration syndrome (MAS) understanding of history, and with the exception of the primary pulmonary surfactant (PS) lack of. ARDS :Pediatric acute respiratory distress syndrome (ARDS) is a severe lung injury caused by pneumonia, sepsis, and trauma.Diagnostic criteria: 1.Acute onset；2.FiO2/ PaO2< 26.7 kPa (200mmHg, ARDS); 3.Chest X-ray showed that the double lung transparent brightness is generally lower, the glass sample, with bronchial inflatable sign, and even double lung field common density increased, the heart shadow is not clear, a white lung, as the most important performance；4. Echocardiography, left atrial hypertension; 5.The gestational age >35 week, have maternal age cholestasis (severe), sepsis or meconium aspiration syndrome (MAS) understanding of history, and with the exception of the primary pulmonary surfactant (PS) lack of；6.Need to use a ventilator. Control group: Patients with mechanical ventilation due to external causes of the lung, no ALI-ARDS performance,FiO2/ PaO2< 40.0 kPa (300 mmHg), such as premature apnea or HIE.

Official Title
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Daping Hospital of the Third Military Medical University

Conditions
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Acute Respiratory Distress Syndrome, Acute Lung Injury, FXR, RIPK3

Intervention / Treatment
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* Other: FXR
* Other: RIPK3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:According to the diagnostic criteria, the diagnosis was ALI or ARDS； Exclusion Criteria:Severe congenital or hereditary disease of the newborn, is clearly diagnosed as NRDS, which is caused by the lack of the primary PS。

Ages Eligible for Study
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Maximum Age: 1 Week

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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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: ALI( acute lung injury)<br>Diagnostic criteria: 1.Acute onset；2.FiO2/ PaO2< 40.0 kPa (300mmHg, ALI); 3.Chest X-ray showed that the double lung texture increased, the increase of crude, fuzzy, visible diffuse patchy infiltration shadow with compensatory emphysema, for the most early performance; B. double lung field large sheet, asymmetric, edge fuzzy infiltration shadow, the most dense in the lung；4. Echocardiography, left atrial hypertension; 5.The gestational age >35 week, have maternal age cholestasis (severe), sepsis or meconium aspiration syndrome (MAS) understanding of history, and with the exception of the primary pulmonary surfactant (PS) lack of. FXR and RIPK3 were measured in neonate with ALI. | Other: FXR<br>* FXR could elevate the transcription of RIPK3, a key protein in necroptosis, and play important role in bile aicd induced alveolar epithelial cell(AEC) necroptosis. FXR were measured in neonate with ALI、ARDS and control<br>Other: RIPK3<br>* FXR(farnesoid-X-receptor) could elevate the transcription of RIPK3, a key protein in necroptosis, and play important role in bile aicd induced alveolar epithelial cell(AEC) necroptosis. RIPK3 were measured in neonate with ALI、ARDS and control.<br>|
| Other: ARDS(respiratory distress syndrome)<br>ARDS :Diagnostic criteria: 1.Acute onset；2.FiO2/ PaO2< 26.7 kPa (200mmHg, ARDS); 3.Chest X-ray showed that the double lung transparent brightness is generally lower, the glass sample, with bronchial inflatable sign, and even double lung field common density increased, the heart shadow is not clear, a white lung, as the most important performance；4. Echocardiography, left atrial hypertension; 5.The gestational age >35 week, have maternal age cholestasis (severe), sepsis or meconium aspiration syndrome (MAS) understanding of history, and with the exception of the primary pulmonary surfactant (PS) lack of；6.Need to use a ventilator. FXR and RIPK3 were measured in neonate with ALI.were measured in another group neonate with ARDS | Other: FXR<br>* FXR could elevate the transcription of RIPK3, a key protein in necroptosis, and play important role in bile aicd induced alveolar epithelial cell(AEC) necroptosis. FXR were measured in neonate with ALI、ARDS and control<br>Other: RIPK3<br>* FXR(farnesoid-X-receptor) could elevate the transcription of RIPK3, a key protein in necroptosis, and play important role in bile aicd induced alveolar epithelial cell(AEC) necroptosis. RIPK3 were measured in neonate with ALI、ARDS and control.<br>|
| Other: control<br>Control group: Patients with mechanical ventilation due to external causes of the lung, no ALI-ARDS performance,FiO2/ PaO2< 40.0 kPa (300 mmHg), such as premature apnea or HIE. FXR and RIPK3 were measured in neonate with HIE | Other: FXR<br>* FXR could elevate the transcription of RIPK3, a key protein in necroptosis, and play important role in bile aicd induced alveolar epithelial cell(AEC) necroptosis. FXR were measured in neonate with ALI、ARDS and control<br>Other: RIPK3<br>* FXR(farnesoid-X-receptor) could elevate the transcription of RIPK3, a key protein in necroptosis, and play important role in bile aicd induced alveolar epithelial cell(AEC) necroptosis. RIPK3 were measured in neonate with ALI、ARDS and control.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FXR |  | 6 hours later | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| chest-X-ray |  | 1 hours later | 
| RIPK3 |  | 6 hours later | 
| blood gas |  | 1 hours later | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FXR, RIPK3, Neonates, Acute Respiratory Distress Syndrome, Acute Lung Injury