Single-nucleus transcriptomic profiling of multiple organs in a rhesus macaque model of SARS-CoV-2 infection

Infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) causes diverse clinical manifestations and tissue injuries in multiple organs.However, cellular and molecular understanding of SARS-CoV-2 infection-associated pathology and immune defense features in different organs remains incomplete. Here, we profiled approximately 77 000single-nucleus transcriptomes of the lung, liver,kidney, and cerebral cortex in rhesus macaques(Macaca mulatta) infected with SARS-CoV-2 and healthy controls. Integrated analysis of the multiorgan dataset suggested that the liver harbored the strongest global transcriptional alterations. We observed prominent impairment in lung epithelial cells, especially in AT2 and ciliated cells, and evident signs of fibrosis in fibroblasts. These lung injury characteristics are similar to those reported in patients with coronavirus disease 2019(COVID-19).Furthermore, we found suppressed MHC class I/II molecular activity in the lung, inflammatory response in the liver, and activation of the kynurenine pathway,which induced the development of an immunosuppressive microenvironment. Analysis of the kidney dataset highlighted tropism of tubule cells to SARS-CoV-2, and we found membranous nephropathy(an autoimmune disease) caused by podocyte dysregulation. In addition, we identified the pathological states of astrocytes and oligodendrocytes in the cerebral cortex, providing molecular insights into COVID-19-related neurological implications. Overall, our multi-organ single-nucleus transcriptomic survey of SARS-CoV-2-infected rhesus macaques broadens our understanding of disease features and antiviral immune defects caused by SARS-CoV-2 infection,which may facilitate the development of therapeutic interventions for COVID-19.

Developmental toxicity and programming alterations of multiple organs in offspring induced by medication during pregnancy

Medication during pregnancy is widespread,but there are few reports on its fetal safety.Recent studies suggest that medication during pregnancy can affect fetal morphological and functional development through multiple pathways,multiple organs,and multiple targets.Its mechanisms involve direct ways such as oxidative stress,epigenetic modification,and metabolic activation,and it may also be indirectly caused by placental dysfunction.Further studies have found that medication during pregnancy may also indirectly lead to multi-organ developmental programming,functional homeostasis changes,and susceptibility to related diseases in offspring by inducing fetal intrauterine exposure to too high or too low levels of maternal-derived glucocorticoids.The organ developmental toxicity and programming alterations caused by medication during pregnancy may also have gender differences and multi-generational genetic effects mediated by abnormal epigenetic modification.Combined with the latest research results of our laboratory,this paper reviews the latest research progress on the developmental toxicity and functional programming alterations of multiple organs in offspring induced by medication during pregnancy,which can provide a theoretical and experimental basis for rational medication during pregnancy and effective prevention and treatment of drug-related multiple fetal-originated diseases.

Fatal multiple acyl-CoA dehydrogenase deficiency caused by ETFDH gene mutation:A case report

BACKGROUND Multiple acyl-CoA dehydrogenase deficiency(MADD)is a disease of rare autosomal recessive disorder.There are three types of MADD.Type I is a neonatalonset form with congenital anomalies.Type II is a neonatal-onset form without congenital anomalies.Type III is considered to a milder form and usually responds to riboflavin.However,late-onset form could also be fatal and not responsive to treatments.CASE SUMMARY We report a severe case of a young man with onset type III MADD induced by drugs and strenuous exercise characterized by rhabdomyolysis and liver dysfunction.Urine analysis indicated 12 out of 70 kinds of organic acids like glutaric acid-2 were detected.Serum analysis in genetic metabolic diseases revealed 24 out of 43 tested items were abnormal,revealing the elevation of several acylcarnitines and the reduction of carnitine in the patient.By next generation sequencing technology for gene sequencing related to fatty acid oxidation and carnitine cycle defects,a rare ETFDH gene variant was identified:NM_004453:4:C.1448C>T(p.Pro483 Leu).The patient was diagnosed with lateonset GAII.He was not responsive to riboflavin and progressively worsened into multiple organ failure that finally led to death.CONCLUSION Type III MADD can also be fatal and not responsive to treatments.

Effects of dexamethasone and Salvia miltiorrhiza on multiple organs in rats with severe acute pancreatitis

Objective:To investigate the protective effects and mechanisms of action of dexamethasone and Salvia miltiorrhiza on multiple organs in rats with severe acute pancreatitis (SAP). Methods:The rats were divided into sham-operated, model control, dexamethasone treated, and Salvia miltiorrhiza treated groups. At 3, 6, and 12 h after operation, the mortality rate of different groups, pathological changes, Bcl-2-associated X protein (Bax) and nuclear factor-κB (NF-κB) protein expression levels in multiple organs (the pancreas, liver, kidneys, and lungs), toll-like receptor 4 (TLR-4) protein levels (only in the liver), intercellular adhesion molecule 1 (ICAM-1) protein levels (only in the lung), and terminal deoxynucleotidy transferase mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) staining expression levels, as well as the serum contents of amylase, glutamate-pyruvate transaminase (GPT), glutamic-oxaloacetic transaminase (GOT), blood urea nitrogen (BUN), and creatinine (CREA) were observed. Results:The mortality rate of the dexamethasone treated group was significantly lower than that of the model control group (P<0.05). The pathological changes in multiple organs in the two treated groups were relieved to different degrees (P<0.05 and P<0.01, respectively), the expression levels of Bax and NF-κB proteins, and apoptotic indexes of multiple organs were reduced (P<0.05 and P<0.01, respectively). The contents of amylase, GPT, GOT, BUN, and CREA in the two treated groups were significantly lower than those in model control groups (P<0.05 and P<0.01, respectively). The expression level of ICAM-1 protein in the lungs (at 3 and 12 h) in the dexamethasone treated group was significantly lower than that in the Salvia miltiorrhiza treated group (P<0.05). The serum contents of CREA (at 12 h) and BUN (at 6 h) of the Salvia miltiorrhiza treated group were significantly lower than those in the dexamethasone treated group (P<0.05). Conclusions:Both dexamethasone and Salvia miltiorrhiza can reduce the inflammatory reaction, regulate apoptosis, and thus protect multiple organs of rats with SAP.

Protective Effects of Radix Astragali Injection on Multiple Organs of Rats with Obstructive Jaundice

Objective： To investigate the protective effects and mechanisms of Radix Astragali Injection on multiple organs of rats with obstructive jaundice（OJ）. Methods： A total of 180 rats were randomly divided into the sham-operated, model control and treated groups（60 in each group）. On 7, 14, 21 and 28 days after operation, the serum contents of alanine aminotransferase（ALT）, aspartate aminotransferase（AST）, r-glutamyl transpeptidase（r-GT）, total bilirubin（TBil）, direct bilirubin（DBil）, blood urine nitrogen（BUN）, and creatinine（CREA） were determined. And the pathological changes of livers, kidneys and lungs, and protein expressions of toll-like receptor-4（TLR-4） of livers, intercellular adhesion molecule-1（ICAM-1） of lungs, Bax and nuclear factor-kappa B（NF-κB）, as well as apoptotic indexes of multiple organs were observed, respectively. Results： The pathological severity scores of multiple organs（including livers on 7, 14, 21 and 28 days, kidneys on 14 and 28 days, and lungs on 14 days）, serum contents of ALT（14 and 21 days）, AST（14 days）, TBil（7, 14, 21 and 28 days）, DBil（14 and 21 days）, BUN（28 days）, protein expressions of TLR-4（in livers, 28 days）, Bax（in livers and kidneys, 21 days）, and apoptotic indexes in livers（7 and 21 days） in the treated group were significantly lower than those in the model control group（P〈0.05 or P〈0.01）. Conclusion： Radix Astragali Injection exerts protective effects on multiple organs of OJ rats by improving the pathological changes of lung, liver and kidney, decreasing the serum index of hepatic and renal function as well as inhibiting the protein expression of TLR-4 and Bax in the livers and Bax in the kidneys.

Full neurological recovery from severe nonexertional heat stroke with multiple organ dysfunction:A case report

BACKGROUND We report a rare case of full neurological recovery from severe nonexertional heat stroke in a 67-year-old woman with an initial Glasgow Coma Scale of 3.This report raises awareness among doctors that when heatstroke is diagnosed,comprehensive treatment should be implemented as soon as possible.Moreover,targeted temperature management,combination therapy with hemodialysis and hemoperfusion,and hyperbaric oxygen therapy may alleviate multiorgan failure and prevent neurological sequelae caused by heatstroke.CASE SUMMARY A previously healthy 67-year-old woman with an initial Glasgow Coma Scale of 3 was found lying prone on the road at noon on a summer day.Laboratory tests revealed multiorgan failure.As soon as heatstroke was diagnosed,comprehensive treatment was implemented.On hospital Day 3,the patient was extubated.Her initial Sequential Organ Failure Assessment score at hospitalization was 14 and decreased to 2 on hospital Day 4.On the seventh day following hospital admission,as the patient’s general condition improved,the levels of laboratory test findings decreased rapidly.Finally,the patient gradually recovered with no other neurological symptoms(the Glasgow Coma Scale at discharge was 15,and her ability to walk independently was restored).CONCLUSION This case demonstrated that targeted temperature management,combination therapy with hemodialysis and hemoperfusion,and hyperbaric oxygen therapy may alleviate multiorgan failure and prevent neurological sequelae caused by heatstroke.

Treatment of a patient with severe lactic acidosis and multiple organ failure due to mitochondrial myopathy:A case report

BACKGROUND Mitochondrial myopathy is a rare genetic disease with maternal inheritance that may involve multiple organ systems.Due to the lack of typical characteristics,its clinical diagnosis is difficult,and it is often misdiagnosed or even missed.CASE SUMMARY The patient was a young college student.When he presented at the hospital,he had severe lactic acidosis,respiratory failure,and shock with multiple organ dysfunction syndrome(MODS).He was treated by mechanical ventilation,venoarterial extracorporeal membrane oxygenation,and other organ support.However,his condition continued to worsen.After a thorough and detailed medical and family history was taken,a mitochondrial crisis was suspected.A muscle biopsy was taken.Further genetic testing confirmed a mitochondrial gene mutation(TRNL13243A>G).The final diagnosis of mitochondrial myopathy was made.Although there is no known specific treatment,intravenous methylprednisone and intravenous immunoglobulin were started.The patient’s shock eventually improved.The further course was complicated by severe infection in multiple sites,severe muscle weakness,and recurrent MODS.After 2 mo of multidisciplinary management and intensive rehabilitation,the patient could walk with assistance 4 mo after admission and walk independently 6 mo after admission.CONCLUSION More attention should be paid to mitochondrial myopathy to avoid missed diagnosis and misdiagnosis.

Preparation method of an ideal model of multiple organ injury of rat with severe acute pancreatitis

AIM： To establish an ideal model of multiple organ injury of rats with severe acute pancreatitis （SAP）.METHODS： SAP models were induced by retrograde injection of 0.1 mL/100 g 3.5% sodium taurocholate into the biliopancreatic duct of Sprague-Dawley rats. The plasma and samples of multiple organ tissues of rats were collected at 3, 6 and 12 h after modeling. The ascites volume, ascites/body weight ratio, and contents of amylase, endotoxin, endothelin-1 （ET-1）, nitrogen monoxidum （NO）, phospholipase A2 （PLA2）, tumor necrosis factor-α （TNF-α）, interleukin-6 （IL-6） in plasma were determined. The histological changes of multiple organs were observed under light microscope.RESULTS： The ascites volume, ascites/body weight ratio, and contents of various inflammatory mediators in blood were higher in the model group than in the sham operation group at all time points [2.38 （1.10）, 2.58 （0.70）, 2.54 （0.71） vs 0.20 （0.04）, 0.30 （0.30）, 0.22 （0.10） at 3, 6 and 12 h in ascites/body weight ratio; 1582 （284）, 1769 （362）, 1618 （302） （U/L） vs 5303 （1373）, 6276 （1029）, 7538 （2934） （U/L） at 3, 6 and 12 h in Amylase; 0.016 （0.005）, 0.016 （0.010）, 0.014 （0.015） （EU/mL） vs 0,053 （0.029）, 0.059 （0.037）, 0.060 （0.022） （EU/mL） at 3, 6 and 12 h in Endotoxin; 3.900 （3.200）, 4.000 （1.700）, 5.300 （3.000） （ng/L） vs 41.438 （37.721）, 92.151 （23.119）, 65.016 （26.806） （ng/L） at 3, 6 and 12 h in TNF-α, all P 〈 0.01]. Visible congestion, edema and lamellar necrosis and massive leukocytic infiltration were found in the pancreas of rats of model group. There were also pathological changes of lung, liver, kidney, ileum, lymphonode, thymus, myocardium and brain.CONCLUSION： This rat model features reliability, convenience and a high achievement ratio. Complicated with multiple organ injury, it is an ideal animal model of SAR

Pathological changes at early stage of multiple organ injury in a rat model of severe acute pancreatitis

BACKGROUND: Severe acute pancreatitis (SAP) is a commonly seen acute abdominal syndrome characterized by sudden onset, rapid progression and high mortality rate. The damage in peripheral organs may be more severe than that in the pancreas, and can even lead to multiple organ dysfunction. It is critical to recognize early pathological changes in multiple organs. This study aimed to assess the early pathological features of damaged organs in a rat model of SAP. METHODS: Thirty clean grade healthy male Sprague-Dawley rats weighing 250-300 g were randomly divided into a model control group (n=15) and a sham-operated group (n=15). The SAP rat model was induced by sodium taurocholate. Samples of blood and from multiple organs were collected 3 hours after operation. We assessed the levels of IL-6, TNF-alpha, PLA2, NO, ET-1, MDA, amylases and endotoxin in blood and observed the early pathological changes in multiple damaged organs. RESULTS: Levels of IL-6, TNF-alpha, PLA2, NO, ET-1 and MDA in serum and of amylase and endotoxin in plasma of the model control group rats were significantly higher than those of the sham-operated group (P<0.01). Different degrees of pathological change were observed in multiple damaged organs. CONCLUSION: Multiple organ injury may occur at the early stage of SAP in rats.

Protective effects of Ligustrazine,Kakonein and Panax Notoginsenoside on the small intestine and immune organs of rats with severe acute pancreatitis

BACKGROUND:Severe acute pancreatitis (SAP) is characterized by fatal pathogenic conditions and a high mortality.It is important to study SAP complicated with multiple organ injury.In this study we compared the protective effects of three traditional Chinese medicines (Ligustrazine,Kakonein and Panax Notoginsenoside) on the small intestine and immune organs (thymus,spleen and lymph nodes) of rats with SAP and explored their mechanism of action.METHODS:One hundred forty-four rats with SAP were randomly divided into model control,Ligustrazine-treated,Kakonein-treated,and Panax Notoginsenoside-treated groups (n=36 per group).Another 36 normal rats comprised the sham-operated group.According to the different time points after operation,the experimental rats in each group were subdivided into 3-,6-and 12-hour subgroups (n=12).At various time points after operation,the mortality rate of rats and pathological changes in the small intestine and immune organs were recorded and the serum amylase levels were measured.RESULTS:Compared to the model control groups,the mortality rates in all treated groups declined and the pathological changes in the small intestine and immune tissues were relieved to different degrees.The serum amylase levels in the three treated groups were significantly lower than those in the model control group at 12 hours.The pathological severity scores for the small intestinal mucosa,thymus and spleen (at 3 and 12 hours) in the Ligustrazine-treated group,for the thymus (at 3 and 12 hours) and spleen (at 3 and 6 hours) in the Kakonein-treated group,and for the thymus (at 3 hours)and spleen (at 3 hours) in the Panax Notoginsenoside-treated group were significantly lower than those in the model control group.The pathological severity scores of the small intestinal mucosa (at 6 and 12 hours) and thymus (at 6 hours) in the Ligustrazine-treated group were significantly lower than those in the Kakonein-and Panax Notoginsenoside-treated groups.CONCLUSIONS:All the three traditional Chinese drugs significantly alleviated the pathological changes in the small intestine and immune organs of SAP rats.Ligustrazine was the most effective one among them.

Impact of interleukin 6 levels on acute lung injury risk and disease severity in critically ill sepsis patients

BACKGROUND Sepsis is a life-threatening condition characterized by a dysregulation of the host response to infection that can lead to acute lung injury(ALI)and multiple organ dysfunction syndrome(MODS).Interleukin 6(IL-6)is a pro-inflammatory cytokine that plays a crucial role in the pathogenesis of sepsis and its complications.AIM To investigate the relationship among plasma IL-6 levels,risk of ALI,and disease severity in critically ill patients with sepsis.METHODS This prospective and observational study was conducted in the intensive care unit of a tertiary care hospital between January 2021 and December 2022.A total of 83 septic patients were enrolled.Plasma IL-6 levels were measured upon admission using an enzyme-linked immunosorbent assay.The development of ALI and MODS was monitored during hospitalization.Disease severity was evaluated by Acute Physiology and Chronic Health Evaluation II(APACHE II)and Sequential Organ Failure Assessment(SOFA)scores.RESULTS Among the 83 patients with sepsis,38(45.8%)developed ALI and 29(34.9%)developed MODS.Plasma IL-6 levels were significantly higher in patients who developed ALI than in those without ALI(median:125.6 pg/mL vs 48.3 pg/mL;P<0.001).Similarly,patients with MODS had higher IL-6 levels than those without MODS(median:142.9 pg/mL vs 58.7 pg/mL;P<0.001).Plasma IL-6 levels were strongly and positively correlated with APACHE II(r=0.72;P<0.001)and SOFA scores(r=0.68;P<0.001).CONCLUSIONElevated plasma IL-6 levels in critically ill patients with sepsis were associated with an increased risk of ALI andMODS.Higher IL-6 levels were correlated with greater disease severity,as reflected by higher APACHE II andSOFA scores.These findings suggest that IL-6 may serve as a biomarker for predicting the development of ALI anddisease severity in patients with sepsis.

Vascular endothelium,a promising target for effectively treating fulminant diquat intoxication?

Following the withdrawal of paraquat,diquat(DQ)has emerged as the predominant herbicide.When people come into contact with or ingest DQ,may lead to poisoning and potentially fatal outcomes.Reports suggest that the mortality of DQ poisoning can be as high as 50%.DQ poisoning can be categorized as mild,moderate to severe or fulminant.In cases of fulminant poisoning,victims often succumb to multiple organ failure within 48 h.This presents a significant challenge in the clinical management.Scholars have discovered that oxidative stress,inflammatory injury,and cell apoptosis play crucial roles in the DQ poisoning.However,the underlying connection of the extensive organ damage remains unknown.The abnormal function and activity of endothelial cells(EC)should play a crucial role in tissue damage caused by DQ due to rich microcirculation and high sensitivity to perfusion in the vulnerable organs.However,reports on DQ-induced EC injury is rare.We made a preliminary discovery-the presence of severe vascular endothelial damage in the kidneys and lungs affected by DQ.Therefore,we hypothesize that DQ poisoning may be attributed to EC damage,ultimately resulting in multiple organ failure.

Exertional heat stroke with pronounced presentation of microangiopathic hemolytic anemia:A case report

BACKGROUND Exertional heat stroke(EHS)is a critical condition arising from prolonged physical exertion in high temperatures that typically presents with normal hemoglobin levels.However,atypical presentations can also occur,leading to significant complications such as hemolytic anemia and organ dysfunction.CASE SUMMARY This case report describes a male patient who experienced moderate-to-severe anemia that was difficult to correct,with a confirmed diagnosis of microangiopathic hemolytic anemia accompanying multiple organ dysfunction syndrome,indicative of critical EHS.Despite intensive resuscitation efforts,the patient’s condition deteriorated,necessitating admission to the intensive care unit for advanced management.CONCLUSION This case highlights the importance of recognizing atypical presentations of EHS,particularly that with significant hemolytic anemia and concurrent organ failure.Clinicians should maintain a high level of suspicion for these complications in patients displaying symptoms of heat-related illness,especially when caused by strenuous activity,as early diagnosis and intervention are crucial to improve patient outcomes.

Extracorporeal organ support for critically ill patients:Overcoming the past,achieving the maximum at present,and redefining the future

Extracorporeal organ support(ECOS)has made remarkable progress over the last few years.Renal replacement therapy,introduced a few decades ago,was the first available application of ECOS.The subsequent evolution of ECOS enabled the enhanced support to many other organs,including the heart[veno-arterial extracorporeal membrane oxygenation(ECMO),slow continuous ultrafiltration],the lungs(veno-venous ECMO,extracorporeal carbon dioxide removal),and the liver(blood purification techniques for the detoxification of liver toxins).Moreover,additional indications of these methods,including the suppression of excessive inflammatory response occurring in severe disorders such as sepsis,coronavirus disease 2019,pancreatitis,and trauma(blood purification techniques for the removal of exotoxins,endotoxins,or cytokines),have arisen.Multiple organ support therapy is crucial since a vast majority of critically ill patients present not with a single but with multiple organ failure(MOF),whereas,traditional therapeutic approaches(mechanical ventilation for acute respiratory failure,antibiotics for sepsis,and inotropes for cardiac dysfunction)have reached the maximum efficacy and cannot be improved further.However,several issues remain to be clarified,such as the complexity and cost of ECOS systems,standardization of indications,therapeutic protocols and initiation time,choice of the patients who will benefit most from these interventions,while evidence from randomized controlled trials supporting their use is still limited.Nevertheless,these methods are currently a part of routine clinical practice in intensive care units.This editorial presents the past,present,and future considerations,as well as perspectives regarding these therapies.Our better understanding of these methods,the pathophysiology of MOF,the crosstalk between native organs resulting in MOF,and the crosstalk between native organs and artificial organ support systems when applied sequentially or simultaneously,will lead to the multiplication of their effects and the minimization of complications arising from their use.

Combined human growth hormone and lactulose for prevention and treatment of multiple organ dysfunction in patients with severe chronic hepatitis B

AIM: To evaluate the efficiency and safety of combined recombinant human growth hormone (rhGH) and lactulose for treatment and/or prevention of multiple organ dysfunction in patients with chronic severe hepatitis B. METHODS: Forty-eight inpatients with chronic severe hepatitis B were randomly divided into rhGH group (n = 28)and control group (n = 20). In rhGH group, 4-4.5 IU of rhGH was injected intramuscularly once daily for 2-4 wk,and 100 mL of enema containing 30 mL of lactulose, 2 g of metronidazole and 0.9% saline was administered every 2 d for 2-4 wk. Their symptoms and complications were noted. Liver and kidney functions were analyzed by an Olympus analyzer. Serum GH, IGF-1, IGFBP1 and IGFBP3 were measured by ELISA.RESULTS: Clinical symptoms of 90% of these patients in rhGH group were obviously improved. The total effectiveness in rhGH group was better than that in control group (75% vs40%, P＜0.05). After 2- and 4-wk treatment of rhGH respectively, serum albumin (26.1±4.1 vs 30.2±5.3,31.9±5.1 g/L), prealbumin (79.6±28.0 vs 106.6±54.4,108.4±55.0 g/L), cholesterol (76.3±16.7 vs 85.6±32.3,96.1±38.7 mg/dL), and IGFBP1 (56.8±47.2 vs 89.7±50.3ng/mL after 2 wk) were significantly increased compared to control group (P＜0.05). However, serum GH was decreased. The increase of serum IGF1 and IGFBP3 after rhGH treatment was also observed.CONCLUSION: rhGH in combination with lactulose may be beneficial to the prevention and treatment of multiple organ dysfunction in patients with chronic severe hepatitis.

Effect of Early Hemofiltration on Pro- and Anti-inflammatory Responses and Multiple Organ Failure in Severe Acute Pancreatitis

The effects of early hemofiltration on the serum levels of cytokines, pro- and anti-inflammatory balance and organ function in pigs with severe acute pancreatits (SAP) were studied. SAP pig model was induced by retrograde injection of artificial bile into the pancreatic duct. The pigs were randomly divided into SAP hemofiltration treatment group (HF group, n=8) and SAP non-hemofiltration treatment group (NHF group, n=8). In the HF group, the animals were subjected to high-volume and zero-balance hemofiltration therapy. The results showed that as compared with NHF group, MAP, CVP and PaO 2/FiO 2 were significantly increased (P<0.01), while HR, urinary protein content, serum ALT level, pulmonary coefficient and lung wet/dry ratio obviously decreased (P<0.05) in HF group. Under a light microscope, the pulmonary histologic scoring was lower that in HF group (P<0.01) and the lesions of renal and liver tissues were milder. However, there was no significant difference in the pancreatic histologic scoring between the two groups. Six h after establishment of the model, the serum levels of TNF-α, IL-1β were lower, while the IL-10/TNF-α ratio was higher in HF group (all P<0.05). It was suggested that early hemofiltration could effectively remove the serum cytokines TNF-α and IL-1β in SAP pigs, elevate the ratio of IL-10/TNF-α, improve hemodynamics and alleviate the lesions of lung, kidney and liver tissues.

PROTECTION OF CARBON MONOXIDE INHALATION ON LIPOPOLY-SACCHARIDE-INDUCED MULTIPLE ORGAN INJURY IN RATS

Objective To observe the protection of carbon monoxide （CO） inhalation on lipopolysaccharide （LPS）-induced rat multiple organ injury. Methods Sprague-Dawley rats with multiple organ injury induced by 5 mg/kg LPS intravenous injection were exposed to room air or 2.5 × 10 ^-4 （V/V） CO for 3 hours. The lung and intestine tissues of rats were harvested to measure the expression of heme oxygenase-1 （ HO-1 ） with reverse transcription-polymerase chain reaction, the levels of pulmonary tumor necrosis factor-or （ TNF-α）, interleukin-6 （ IL-6）, and intestinal platelet activator factor （ PAF）, intercellular adhesion molecule-1 （ICAM-1） with enzyme-linked immunosorbent assay, the content of maleic dialdehyde （MDA） and the activity of myeloperoxidase （MPO） with chemical method, the cell apoptosis rate with flow cytometry, and the pathological changes with light microscope. Results CO inhalation obviously up-regulated the expression of HO-1 in lung （5.43 ± 0. 92） and intestine （6. 29 ± 1.56） in LPS ＋ CO group compared with （ 3.08 ± 0. 82） and （ 3.97 ± 1.16 ） in LPS group （ both P 〈 0. 05 ）. The levels of TNF-ot, IL-6 in lung and PAF, ICAM-1 in intestine ofLPS ＋ CO group were 0. 91 ±0. 25,0. 64 ±0.05, 1. 19 ± 0. 52, and 1.83 ±0. 35 pg/mg, respectively, significantly lower than the corresponding values in LPS group （ 1.48 ± 0. 23, 1.16 ± 0. 26, 1.84 ± 0. 73, and 3.48 ± 0. 36 pg/mg, all P 〈 0. 05 ）. The levels of MDA, MPO, and cell apoptosis rate in lung and intestine of LPS ＋ CO group were 1.02 ± 0. 23 nmol/mg, 1.74 ± 0. 17 nmol/mg, 7.18 ± 1.62 U/mg, 6. 30 ±0. 97 U/mg, 1.60% ±0. 34%, and 30. 56% ±6. 33%, respectively, significantly lower than the corresponding values in LPS group （ 1.27 ± 0. 33 nmol/mg, 2. 75 ± 0. 39 nmol/mg, 8. 16 ± 1.49 U/mg, 7. 72 ± 1.07 U/mg, 3.18% ±0. 51%, and 41.52% -＋3.36%, all P 〈0.05）. In addition, injury of lung and intestine induced by LPS was attenuated at presence of CO inhalation. Conclusion CO inhalation protects rat lung and intestine from LPS-induced injury via anti-oxidantion, anti-inflammation, anti-apoptosis, and up-regulation of HO-1 expression.

Morphological changes in interstitial cells of Cajal in the deep muscular plexus and enteric motor neurons of the intestine in rats with multiple organ dysfunction syndrome

BACKGROUND：Gastrointestinal motility dysfunction in multiple organ dysfunction syndrome （MODS） has been reported to be related to damage to interstitial cells of Cajal （ICC）. In the entedc nervous system, ICC and smooth muscle cells are connected in a network to form a special functional unit. Many gastrointestinal motility dysfunction diseases are associated with damage to this network.OBJECTIVE：To investigate the morphological changes of intestinal ICC, and to explore the mechanisms underlying gastrointestinal motility dysfunction in rats with MODS.DESIGN, TIME AND SE＇I-FING：The randomized, controlled, experiment was performed at the Central Laboratory of the First Affiliated Hospital of Dalian Medical University of China between June 2007 and March 2009.MATERIALS：Escherichia coli （E. colistrain O127 H6） and bovine serum albumin were purchased from Sigma, USA.METHODS：A total of 40 Wistar rats were equally and randomly divided into MODS group and control group. Suspension of E. coil strain O127 H6 containing BaSO4 and saline were sterilely injected into the abdominal cavity of rats in the MODS and control groups, respectively.MAIN OUTCOME MEASURES：Immunohistochemical double-staining and confocal laser scanning microscopy were used to observe the morphological changes in intestinal cholinergic nerves and ICC in the deep muscular plexus network. Electron microscopy was employed to evaluate the ultrastructural features of ICC in the deep muscular plexus of rats with MODS.RESULTS：Compared with the control group, the distributions and densities of cholinergic/nitrergic newes and ICC in the deep muscular plexus were significantly decreased in the MODS group （P 〈 0.01）. The enteric nerve-ICC network were disrupted.CONCLUSION：There is ultrastructural injury in the ICC in the deep muscular plexus and enteric nerves of the intestine in rats with MODS, which may be associated with the dysmotility of the gastrointestinal tract in MODS.

Mild hypothermia in improving multiple organ dysfunction after cardiac arrest

BACKGROUND： Resuscitation after cardiac arrest （CA） with a whole-body ischemia–reperfusion injury causes brain injury and multiple organ dysfunction （MODS）. This study aimed to determine whether mild systemic hypothermia could decrease multiple organ dysfunctions after resuscitation from cardiac arrest.METHODS： The patients who had been resuscitated after cardiac arrest were reviewed. During the resuscitation they had been assigned to undergo therapeutic hypothermia （target temperature, 32°C to 34°C, measured in the rectum） over a period of 24 to 36 hours or to receive standard treatment with normothermia. Markers of different organ injury were evaluated for the ？ rst 72 hours after recovery of spontaneous circulation （ROSC）.RESULTS： At 72 hours after ROSC, 23 patients in the hypothermia group for whom data were available had favorable neurologic, myocardial, hepatic and pulmonic outcomes as compared with 26 patients in the normothermia group. The values of renal function were not signi？ cantly different between the two groups. However, blood coagulation function was badly injured in the hypothermia group.CONCLUSION： In the patients who have been successfully resuscitated after cardiac arrest, therapeutic mild hypothermia can alleviate dysfunction after resuscitation from cardiac arrest.

Clinical Effects of Intensive Insulin Therapy Treating Traumatic Shock Combined with Multiple Organ Dysfunction Syndrome

The therapeutic effects of intensive insulin therapy in treatment of traumatic shock combined with multiple organ dysfunction syndrome （MODS） were investigated. A total of 114 patients with traumatic shock combined with MODS were randomly divided into two groups： control group （n=56） treated with conventional therapy, and intensive insulin therapy group （n=58） treated with conventional therapy plus continuous insulin pumping to control the blood glucose level at range of 4.4-6.1 mmol/L. White blood cells （WBC） counts, prothrombin time （PT）, serum creatinine （SCr）, alanine aminotransferase （ALT）, serum albumin and PaO2 were measured before and at the day 1, 3, 5, 7 and 14 after treatment. The incidence of gastrointestinal dysfunction, the incidence of MODS, hospital stay and the mortality were also observed and compared. After intensive insulin therapy, the WBC counts, SCr, ALT and PT were significantly reduced （P0.05）, but the level of serum albumin was significantly increased （P0.05） at the day 3, 5, 7 and 14. In the meantime, the PaO2 was significantly elevated at the day 3, 5 and 7 （P0.01） after intensive insulin therapy. The incidence of gastrointestinal dysfunction, the incidence of MODS, the length of hospital stay and the mortality were markedly decreased （P0.01）. The results suggest early treatment with intensive insulin therapy is effective for traumatic shock combined with MODS and can decrease the length of hospital stay and the mortality.