<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04455061</url>
  </required_header>
  <id_info>
    <org_study_id>2020-01-01</org_study_id>
    <nct_id>NCT04455061</nct_id>
  </id_info>
  <brief_title>Intestinal Flora Research Plan for Critically Ill Patients</brief_title>
  <official_title>Intestinal Flora Research Plan for Critically Ill Patients-- Study on the Relationship Between Microbial Disorder and Disease Severity, Prognosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chinese Medical Association</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chinese Medical Association</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      More and more critically ill patients have improved early survival, they have been suffering&#xD;
      from organ damage and inflammation for a long time, which is called chronic critical illness&#xD;
      (CCI). Among CCI, persistent inflammatory response-immunosuppression-catabolic syndrome&#xD;
      (PICS) is a special type of chronic severe disease, and immune paralysis is its main feature.&#xD;
      The clinical manifestations are repeated nosocomial infections, malnutrition, muscle loss,&#xD;
      and difficulty in wound healing and require long-term emergency medical support, which&#xD;
      ultimately leads to patients Repeated nosocomial infections, prolonged hospitalization, and&#xD;
      increased mortality.&#xD;
&#xD;
      The gut provides the microbiome with habitat and the nutrients it needs, down-regulates the&#xD;
      immune response to form immune tolerance, and promotes its colonization in the&#xD;
      intestine.Under physiological conditions, the mutually beneficial symbiosis of the intestine&#xD;
      and microorganisms promotes the body's homeostasis. The composition and biodiversity of the&#xD;
      microbial community are highly susceptible to various factors, including diet, environment,&#xD;
      drugs, infections, inflammation, etc. Especially for acute stress, severe stress, the use of&#xD;
      broad-spectrum antibiotics, vasoconstrictors and opioids, intestinal ischemia/reperfusion&#xD;
      injury, epithelial cell apoptosis, barrier integrity destruction, gastrointestinal Changes in&#xD;
      the motility of the tract, lack of nutrients in the intestinal cavity, etc. All those can&#xD;
      lead to rapid changes in the intestinal flora, and this change can last for a long time;&#xD;
      manifested by the loss of the richness and diversity of the intestinal microflora (especially&#xD;
      the symbiotic flora), The ratio of Bacteroidetes/thickwalled bacteria is severely unbalanced,&#xD;
      and a single flora (often a potential pathogen) overgrows, that is, bacterial flora imbalance&#xD;
      or microecological disturbance.&#xD;
&#xD;
      At present, for critically ill patients, there are few relevant studies, and currently&#xD;
      limited to small-scale, single cross-sectional studies. These studies have uncovered the&#xD;
      changes and impacts of intestinal microbiota in critically ill patients in ICU, but they are&#xD;
      still in the stage of touching the image of blind people. The relevant mechanisms and dynamic&#xD;
      changes and their significance are unclear, requiring large-scale, dynamic, continuous and&#xD;
      comprehensive In order to accurately grasp the role of intestinal flora in the development&#xD;
      and prognosis of the disease, we hope to accurately control the intestinal flora and achieve&#xD;
      effective treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      With the improvement and development of medical technology and concepts, the types,&#xD;
      progression, and outcomes of critically ill patients have changed dramatically. More and more&#xD;
      critically ill patients can successfully escape from the early critical state, and the&#xD;
      outbreak of multiple organ failure has been alleviated. However, due to the residual organ&#xD;
      dysfunction, the number of cases staying in the intensive care department for a long time is&#xD;
      increasing. Both severe trauma and sepsis undergo similar transformations. Although these&#xD;
      patients have improved early survival, they have been suffering from organ damage and&#xD;
      inflammation for a long time, which is called chronic critical illness (CCI). The definition&#xD;
      of CCI includes the number of days of ICU hospitalization greater than or equal to 14 days,&#xD;
      evidence of persistent organ dysfunction, and can be measured using components of the 14-day&#xD;
      Sequential Organ Failure Assessment (SOFA) score. Even nearly 40% of sepsis patients will&#xD;
      develop CCI. These critical survivors continue to recover and support treatment even after&#xD;
      being discharged from the hospital, often failing to recover and eventually die. Among them,&#xD;
      persistent inflammatory response-immunosuppression-catabolic syndrome (PICS) is a special&#xD;
      type of chronic severe disease, and immune paralysis is its main feature. These patients also&#xD;
      face several challenges such as persistent inflammatory response, acquired immunosuppression,&#xD;
      and high catabolism. The clinical manifestations are repeated nosocomial infections,&#xD;
      malnutrition, muscle loss, and difficulty in wound healing and require long-term emergency&#xD;
      medical support, which ultimately leads to patients Repeated nosocomial infections, prolonged&#xD;
      hospitalization, and increased mortality.&#xD;
&#xD;
      Due to the decline in organ function reserve of elderly patients, chronic diseases of basic&#xD;
      heart, lung, kidney and other systems are often combined. After suffering trauma and severe&#xD;
      infection, organ function disorders or failures are prone to occur and stay in the ICU ward.&#xD;
      With the advent of an aging population, such patients are increasing year by year. It is a&#xD;
      heavy burden on society and a huge challenge for the future development and progress of ICU.&#xD;
&#xD;
      The gut flora is involved in a wide range of functions, food digestion, hormone production,&#xD;
      and the development and maturation of the immune system. After more than a billion years of&#xD;
      co-evolution, a stable symbiotic relationship has been formed between mammals including&#xD;
      humans and the gut microbiota. The gut provides the microbiome with habitat and the nutrients&#xD;
      it needs, down-regulates the immune response to form immune tolerance, and promotes its&#xD;
      colonization in the intestine; accordingly, the gut symbiotic microbiota promotes the health&#xD;
      of the body in various ways to form symbiosis Mode: (1) Inhibiting the colonization of&#xD;
      pathogenic bacteria by competing for niche and nutrients, producing virulence factors, and&#xD;
      secreting bacteriocins, preventing their overgrowth, and protecting the body from pathogen&#xD;
      infection, called colonization resistance; (2 ) Promote the proliferation of epithelial&#xD;
      cells, secrete antimicrobial peptides and mucus to maintain the integrity of the intestinal&#xD;
      barrier; (3) Indirectly regulate the differentiation of innate and adaptive immune cells&#xD;
      located in the intestinal epithelial barrier and the whole body, promote the development and&#xD;
      maturation of the immune system, and strengthen immune cells Function; (4) Induce&#xD;
      extravascular tissue factor-protease activated receptor 1 (TF-PAR1) signal transduction,&#xD;
      promote small intestine angiogenesis; (5) participate in hormone signal transduction,&#xD;
      regulate intestinal endocrine function; (6) participate in intestinal origin Serotonin (5-HT)&#xD;
      metabolism and intestinal neuro-immune cooperation, regulate gastrointestinal motility; (7)&#xD;
      produce short-chain fatty acids (SCFAs) by fermenting dietary fiber, improve glucose&#xD;
      homeostasis and insulin sensitivity, participate in anti-inflammatory, Promote intestinal&#xD;
      motility; (8) Synthesize essential vitamins and neurotransmitters and metabolize bile salts;&#xD;
      (9) Participate in body drug metabolism and poison removal. This shows that under&#xD;
      physiological conditions, the mutually beneficial symbiosis of the intestine and&#xD;
      microorganisms promotes the body's homeostasis. The composition and biodiversity of the&#xD;
      microbial community are highly susceptible to various factors, including diet, environment,&#xD;
      drugs, infections, inflammation, etc. Especially for acute stress, severe stress, the use of&#xD;
      broad-spectrum antibiotics, vasoconstrictors and opioids, intestinal ischemia/reperfusion&#xD;
      injury, epithelial cell apoptosis, barrier integrity destruction, gastrointestinal Changes in&#xD;
      the motility of the tract, lack of nutrients in the intestinal cavity, etc. lead to rapid&#xD;
      changes in the intestinal flora, and this change can last for a long time; manifested by the&#xD;
      loss of the richness and diversity of the intestinal microflora (especially the symbiotic&#xD;
      flora), The ratio of Bacteroidetes/thickwalled bacteria is severely unbalanced, and a single&#xD;
      flora (often a potential pathogen) overgrows, that is, bacterial flora imbalance or&#xD;
      microecological disturbance.&#xD;
&#xD;
      The local immune inflammatory storm in the intestine is an important cause of the imbalance&#xD;
      of the systemic immune inflammatory response, and the hypothalamic metabolism center is an&#xD;
      important target for regulating the body's continuous catabolism. In PICS, immunosuppression,&#xD;
      inflammation, and catabolism are mutually causal, forming a vicious circle. So what is the&#xD;
      reason for severe patients with different primary diseases to have the same PICS after the&#xD;
      acute phase? Are there common pathological changes induced by PICS in severe patients? If&#xD;
      further studies can be made to clarify the initiating factors of PICS and the path of&#xD;
      occurrence and development of PICS, it is undoubtedly a new breakthrough in the treatment of&#xD;
      PICS and the &quot;fundamental&quot; way to reduce the mortality of PICS patients. Combining our&#xD;
      previous research results, applicants speculate as follows:&#xD;
&#xD;
      1. The intestinal tract is the &quot;promoting point&quot; for the occurrence of PICS in severely ill&#xD;
      patients, and it is also the &quot;central organ&quot; that promotes the development of the disease; 2.&#xD;
      The disturbance of the micro-ecology of the intestinal tract is an important reason for&#xD;
      causing PICS in the body (and may even be the decisive factor) ; 3. Correction of intestinal&#xD;
      microecological disturbances can effectively block the path of PICS development.&#xD;
&#xD;
      For the above ideas, specific explanations are as follows:&#xD;
&#xD;
        1. The intestine may be the &quot;promoting point&quot; for PICS in critically ill patients, and it&#xD;
           is also the &quot;central organ&quot; that promotes the development of the disease. The reasons&#xD;
           are as follows:&#xD;
&#xD;
             -  Our previous studies showed that acute gastrointestinal dysfunction is common in&#xD;
                severe patients. Whether it is local simple abdominal exposure injury or systemic&#xD;
                ischemia-reperfusion injury, it can cause acute gastrointestinal dysfunction; ②The&#xD;
                intestine is not only the main organ of digestion and absorption, but also the&#xD;
                body's largest immune organ (adult). When the intestine is acutely damaged, the&#xD;
                intestine can affect the nutritional metabolism center of the hypothalamus through&#xD;
                Grelin and other hormones, leading to refractory catabolism and exogenous&#xD;
                nutrition. At the same time, the local inflammatory reaction of the intestinal&#xD;
                tract can also cause an imbalance of the body's immune inflammatory response. In&#xD;
                addition, changes in central metabolism in critically ill patients are related to&#xD;
                hypothalamic inflammation (indicating that the intestine is &quot;capable&quot; to become the&#xD;
                central organ that promotes the occurrence and development of PICS).&#xD;
&#xD;
      Intestinal microecological disturbance is an important cause of PICS Under normal&#xD;
      physiological conditions, the intestine has powerful barrier functions, such as physical&#xD;
      barrier, chemical barrier, immune barrier, and biological barrier. Especially its biological&#xD;
      barrier function plays an important role in the body's metabolism and immunity. There is a&#xD;
      stable symbiotic relationship between the human body and the intestinal microbiota. The&#xD;
      intestine provides the microbiome with habitat and the nutrients it needs to downregulate the&#xD;
      immune response to form immune tolerance and promote its colonization in the intestine;&#xD;
      accordingly, the physiological state Next, the gut symbiotic microbiota also maintains the&#xD;
      body's health in various ways [2]. The intestine and microorganisms are symbiotic and promote&#xD;
      the body's homeostasis. However, the composition and biodiversity of the microbial community&#xD;
      are highly susceptible to various factors, including diet, environment, drugs, infections,&#xD;
      inflammation, etc.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 1, 2020</start_date>
  <completion_date type="Anticipated">December 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2022</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>1 Month</target_duration>
  <primary_outcome>
    <measure>28-day mortality</measure>
    <time_frame>up to 28 days after hospitalized.</time_frame>
    <description>The patient's 28-day mortality rate is the survival rate from the onset to the disease at 28 days, compared with the total number of illnesses, to assess the severity of the disease</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>the duration of intensive care unit</measure>
    <time_frame>Up to 8 weeks</time_frame>
    <description>time for patients treatment in intensive care unit is patient total treated days in intensive care unit.</description>
  </secondary_outcome>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Gut Microbiota, PICS</condition>
  <eligibility>
    <study_pop>
      <textblock>
        In order to further understand and grasp the relationship between the intestinal microflora&#xD;
        in critically ill patients, the relationship with the progression of critical illness, the&#xD;
        outcome of the disease and the final prognosis, it is now planned to analyze the dynamic&#xD;
        intestinal microflora changes in critically ill patients through 16SrRNA technology.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18-75 years old&#xD;
&#xD;
          2. Expect to stay in the ICU for more than 7 days after enrollment;&#xD;
&#xD;
          3. Initial disease, not receiving ICU special treatment;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Does not meet the inclusion criteria;&#xD;
&#xD;
          2. Complicated with perianal infection, intestinal fistula, short bowel syndrome, chronic&#xD;
             severe gastrointestinal disease;&#xD;
&#xD;
          3. Patients with malignant tumors undergoing chemotherapy and radiotherapy;&#xD;
&#xD;
          4. Taking probiotic preparations within the past 3 months, etc. Intestinal flora&#xD;
             regulator.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>The Affliated Drum Tower Hospital, Medical School of Nanjing University</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <zip>210008</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wenkui Yu</last_name>
      <phone>02568182222</phone>
      <phone_ext>60506</phone_ext>
      <email>yudrnj@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>June 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 2, 2020</study_first_posted>
  <last_update_submitted>June 29, 2020</last_update_submitted>
  <last_update_submitted_qc>June 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Critical Illness</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04455061
org study id: 2020-01-01
nct id: NCT04455061
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
More and more critically ill patients have improved early survival, they have been suffering
      from organ damage and inflammation for a long time, which is called chronic critical illness
      (CCI). Among CCI, persistent inflammatory response-immunosuppression-catabolic syndrome
      (PICS) is a special type of chronic severe disease, and immune paralysis is its main feature.
      The clinical manifestations are repeated nosocomial infections, malnutrition, muscle loss,
      and difficulty in wound healing and require long-term emergency medical support, which
      ultimately leads to patients Repeated nosocomial infections, prolonged hospitalization, and
      increased mortality.

      The gut provides the microbiome with habitat and the nutrients it needs, down-regulates the
      immune response to form immune tolerance, and promotes its colonization in the
      intestine.Under physiological conditions, the mutually beneficial symbiosis of the intestine
      and microorganisms promotes the body's homeostasis. The composition and biodiversity of the
      microbial community are highly susceptible to various factors, including diet, environment,
      drugs, infections, inflammation, etc. Especially for acute stress, severe stress, the use of
      broad-spectrum antibiotics, vasoconstrictors and opioids, intestinal ischemia/reperfusion
      injury, epithelial cell apoptosis, barrier integrity destruction, gastrointestinal Changes in
      the motility of the tract, lack of nutrients in the intestinal cavity, etc. All those can
      lead to rapid changes in the intestinal flora, and this change can last for a long time;
      manifested by the loss of the richness and diversity of the intestinal microflora (especially
      the symbiotic flora), The ratio of Bacteroidetes/thickwalled bacteria is severely unbalanced,
      and a single flora (often a potential pathogen) overgrows, that is, bacterial flora imbalance
      or microecological disturbance.

      At present, for critically ill patients, there are few relevant studies, and currently
      limited to small-scale, single cross-sectional studies. These studies have uncovered the
      changes and impacts of intestinal microbiota in critically ill patients in ICU, but they are
      still in the stage of touching the image of blind people. The relevant mechanisms and dynamic
      changes and their significance are unclear, requiring large-scale, dynamic, continuous and
      comprehensive In order to accurately grasp the role of intestinal flora in the development
      and prognosis of the disease, we hope to accurately control the intestinal flora and achieve
      effective treatment.
With the improvement and development of medical technology and concepts, the types,
      progression, and outcomes of critically ill patients have changed dramatically. More and more
      critically ill patients can successfully escape from the early critical state, and the
      outbreak of multiple organ failure has been alleviated. However, due to the residual organ
      dysfunction, the number of cases staying in the intensive care department for a long time is
      increasing. Both severe trauma and sepsis undergo similar transformations. Although these
      patients have improved early survival, they have been suffering from organ damage and
      inflammation for a long time, which is called chronic critical illness (CCI). The definition
      of CCI includes the number of days of ICU hospitalization greater than or equal to 14 days,
      evidence of persistent organ dysfunction, and can be measured using components of the 14-day
      Sequential Organ Failure Assessment (SOFA) score. Even nearly 40% of sepsis patients will
      develop CCI. These critical survivors continue to recover and support treatment even after
      being discharged from the hospital, often failing to recover and eventually die. Among them,
      persistent inflammatory response-immunosuppression-catabolic syndrome (PICS) is a special
      type of chronic severe disease, and immune paralysis is its main feature. These patients also
      face several challenges such as persistent inflammatory response, acquired immunosuppression,
      and high catabolism. The clinical manifestations are repeated nosocomial infections,
      malnutrition, muscle loss, and difficulty in wound healing and require long-term emergency
      medical support, which ultimately leads to patients Repeated nosocomial infections, prolonged
      hospitalization, and increased mortality.

      Due to the decline in organ function reserve of elderly patients, chronic diseases of basic
      heart, lung, kidney and other systems are often combined. After suffering trauma and severe
      infection, organ function disorders or failures are prone to occur and stay in the ICU ward.
      With the advent of an aging population, such patients are increasing year by year. It is a
      heavy burden on society and a huge challenge for the future development and progress of ICU.

      The gut flora is involved in a wide range of functions, food digestion, hormone production,
      and the development and maturation of the immune system. After more than a billion years of
      co-evolution, a stable symbiotic relationship has been formed between mammals including
      humans and the gut microbiota. The gut provides the microbiome with habitat and the nutrients
      it needs, down-regulates the immune response to form immune tolerance, and promotes its
      colonization in the intestine; accordingly, the gut symbiotic microbiota promotes the health
      of the body in various ways to form symbiosis Mode: (1) Inhibiting the colonization of
      pathogenic bacteria by competing for niche and nutrients, producing virulence factors, and
      secreting bacteriocins, preventing their overgrowth, and protecting the body from pathogen
      infection, called colonization resistance; (2 ) Promote the proliferation of epithelial
      cells, secrete antimicrobial peptides and mucus to maintain the integrity of the intestinal
      barrier; (3) Indirectly regulate the differentiation of innate and adaptive immune cells
      located in the intestinal epithelial barrier and the whole body, promote the development and
      maturation of the immune system, and strengthen immune cells Function; (4) Induce
      extravascular tissue factor-protease activated receptor 1 (TF-PAR1) signal transduction,
      promote small intestine angiogenesis; (5) participate in hormone signal transduction,
      regulate intestinal endocrine function; (6) participate in intestinal origin Serotonin (5-HT)
      metabolism and intestinal neuro-immune cooperation, regulate gastrointestinal motility; (7)
      produce short-chain fatty acids (SCFAs) by fermenting dietary fiber, improve glucose
      homeostasis and insulin sensitivity, participate in anti-inflammatory, Promote intestinal
      motility; (8) Synthesize essential vitamins and neurotransmitters and metabolize bile salts;
      (9) Participate in body drug metabolism and poison removal. This shows that under
      physiological conditions, the mutually beneficial symbiosis of the intestine and
      microorganisms promotes the body's homeostasis. The composition and biodiversity of the
      microbial community are highly susceptible to various factors, including diet, environment,
      drugs, infections, inflammation, etc. Especially for acute stress, severe stress, the use of
      broad-spectrum antibiotics, vasoconstrictors and opioids, intestinal ischemia/reperfusion
      injury, epithelial cell apoptosis, barrier integrity destruction, gastrointestinal Changes in
      the motility of the tract, lack of nutrients in the intestinal cavity, etc. lead to rapid
      changes in the intestinal flora, and this change can last for a long time; manifested by the
      loss of the richness and diversity of the intestinal microflora (especially the symbiotic
      flora), The ratio of Bacteroidetes/thickwalled bacteria is severely unbalanced, and a single
      flora (often a potential pathogen) overgrows, that is, bacterial flora imbalance or
      microecological disturbance.

      The local immune inflammatory storm in the intestine is an important cause of the imbalance
      of the systemic immune inflammatory response, and the hypothalamic metabolism center is an
      important target for regulating the body's continuous catabolism. In PICS, immunosuppression,
      inflammation, and catabolism are mutually causal, forming a vicious circle. So what is the
      reason for severe patients with different primary diseases to have the same PICS after the
      acute phase? Are there common pathological changes induced by PICS in severe patients? If
      further studies can be made to clarify the initiating factors of PICS and the path of
      occurrence and development of PICS, it is undoubtedly a new breakthrough in the treatment of
      PICS and the "fundamental" way to reduce the mortality of PICS patients. Combining our
      previous research results, applicants speculate as follows:

      1. The intestinal tract is the "promoting point" for the occurrence of PICS in severely ill
      patients, and it is also the "central organ" that promotes the development of the disease; 2.
      The disturbance of the micro-ecology of the intestinal tract is an important reason for
      causing PICS in the body (and may even be the decisive factor) ; 3. Correction of intestinal
      microecological disturbances can effectively block the path of PICS development.

      For the above ideas, specific explanations are as follows:

        1. The intestine may be the "promoting point" for PICS in critically ill patients, and it
           is also the "central organ" that promotes the development of the disease. The reasons
           are as follows:

             -  Our previous studies showed that acute gastrointestinal dysfunction is common in
                severe patients. Whether it is local simple abdominal exposure injury or systemic
                ischemia-reperfusion injury, it can cause acute gastrointestinal dysfunction; ②The
                intestine is not only the main organ of digestion and absorption, but also the
                body's largest immune organ (adult). When the intestine is acutely damaged, the
                intestine can affect the nutritional metabolism center of the hypothalamus through
                Grelin and other hormones, leading to refractory catabolism and exogenous
                nutrition. At the same time, the local inflammatory reaction of the intestinal
                tract can also cause an imbalance of the body's immune inflammatory response. In
                addition, changes in central metabolism in critically ill patients are related to
                hypothalamic inflammation (indicating that the intestine is "capable" to become the
                central organ that promotes the occurrence and development of PICS).

      Intestinal microecological disturbance is an important cause of PICS Under normal
      physiological conditions, the intestine has powerful barrier functions, such as physical
      barrier, chemical barrier, immune barrier, and biological barrier. Especially its biological
      barrier function plays an important role in the body's metabolism and immunity. There is a
      stable symbiotic relationship between the human body and the intestinal microbiota. The
      intestine provides the microbiome with habitat and the nutrients it needs to downregulate the
      immune response to form immune tolerance and promote its colonization in the intestine;
      accordingly, the physiological state Next, the gut symbiotic microbiota also maintains the
      body's health in various ways [2]. The intestine and microorganisms are symbiotic and promote
      the body's homeostasis. However, the composition and biodiversity of the microbial community
      are highly susceptible to various factors, including diet, environment, drugs, infections,
      inflammation, etc.
observational model: Case-Control
time perspective: Prospective
measure: 28-day mortality
time frame: up to 28 days after hospitalized.
description: The patient's 28-day mortality rate is the survival rate from the onset to the disease at 28 days, compared with the total number of illnesses, to assess the severity of the disease
measure: the duration of intensive care unit
time frame: Up to 8 weeks
description: time for patients treatment in intensive care unit is patient total treated days in intensive care unit.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Critical Illness