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.

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.

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.

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.

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

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.

Magnetic resonance imaging correlates of bee sting induced multiple organ dysfunction syndrome: A case report

Occasionally systemic complications with high risk of death,such as multiple organ dysfunction syndrome(MODS),can occur following multiple bee stings.This case study reports a patient who presented with MODS,i.e.,acute kidney injury,hepatic and cardiac dysfunc-tion,after multiple bee stings.The standard clinical findings were then correlated with magnetic resonance imaging(MRI)findings,which demonstrates that MRI may be utilized as a simpler tool to use than other mul-tiple diagnostics.

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.

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.

Animal model of non-bacterial multiple organ dysfunction syndrome in the elderly

Objective To establish a model of multiple organ dysfunction syndrome in the elderly (MODSE) by intraperitoneal injection of different doses of zymosan, and to compare the multiple organ dysfunction syndrome (MODS) in adult and in the elderly rats. Methods Adult and senile rats, injected with different doses of zymosan intraperitoneally were examined for the changes in the function and morphology of the vital organs, including heart, liver, brain, lungs, and kidneys using blood gas and biochemistry analysis and histopathological examination methods. Results Compared with the normal controls of the adult and the elderly rats, the blood gas and blood biochemistry changed in different degrees in the different dosed zymosan groups. Pathological changes were also found in the vital organs including lungs, heart, liver, brain, kidneys, erc in the experimental groups. Under the same concentrations of zymosan, the reductions in respiratory, cardiac and renal functions in the senile groups were much more severe than those in the corresponding adult group. In the similar degree of model duplication, the senile rats had the tendency to die later than the adult rats. Conclusions Zymosan can be used in both elderly and adult rats to induce MODS model, and the best dosage for MODSE was 0.Sg/kg injected peritoneally. The model would hopefully be used in the study of mechanisms and the therapeutics on MODSE.

Application of bedside continuous blood purification in patients with multiple organ dysfunction syndromes

BACKGROUND:The complications of systemic inflammatory response syndrome(SIRS)include acute lung injury,acute kidney injury,shock,and multiple organ dysfunction syndrome(MODS).In recent years,how to clear inflammatory mediators has become a hot topic in critical care medicine.Researchers hypothesize that continuous blood purification(CBP) can effectively eliminate a variety of inflammatory mediators which participate in the occurrence of MODS and adjust the immune imbalance.This study aimed to observe the effects of CBP in MODS patients.METHODS:In this retrospective clinical study,a total of 38 MODS patients,18 males and 20 females,were enrolled.After conventional therapy,all the patients received CBP.Biochemistry,blood gas analysis,oxygenation index,mean arterial blood pressure(MAP),acute physiology and chronic health evaluation(APACHE) II scores were monitored.RESULTS:After CBP,the vital signs of patients were rapidly stable,and electrolyte disorders and acid-base imbalance were corrected.Renal function,blood gas,oxygenation index were all improved.MAP was increased,and APACHE II score was significantly decreased.All patients had good tolerance,stable hemodynamics,and no obvious adverse reaction on CBP compared with pre-CBP.CONCLUSION:CBP can effectively clean toxins,correct electrolyte acid-base balance,and improve systemic inflammatory response syndrome and the organ function of MODS patients.

Development of multiple soft computing models for estimating organic and inorganic constituents in coal

The distribution of the various organic and inorganic constituents and their influences on the combustion of coal has been comprehensively studied.However,the combustion characteristics of pulverized coal depend not only on rank but also on the composition,distribution,and combination of the macerals.Unlike the proximate and ultimate analyses,determining the macerals in coal involves the use of sophisticated microscopic instrumentation and expertise.In this study,an attempt was made to predict the amount of macerals(vitrinite,inertinite,and liptinite)and total mineral matter from the Witbank Coalfields samples using the multiple input single output white-box artificial neural network(MISOWB-ANN),gene expression programming(GEP),multiple linear regression(MLR),and multiple nonlinear regression(MNLR).The predictive models obtained from the multiple soft computing models adopted are contrasted with one another using difference,efficiency,and composite statistical indicators to examine the appropriateness of the models.The MISOWB-ANN provides a more reliable predictive model than the other three models with the lowest difference and highest efficiency and composite statistical indicators.

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.

Blood hemoperfusion with resin adsorption combined continuous veno-venous hemofiltration for patients with multiple organ dysfunction syndrome

BACKGROUND:Blood hemoperfusion with resin adsorption can clean larger molecules that exceed the molecular weight cutoff of combined continuous veno-venous hemofiltration(CWH).Hence blood hemoperfusion with resin adsorption combined CWH(HP+CWH) has higher ability of mediator clearance,and can improve clinical outcomes in theory.This study aimed to investigate the effect of blood hemoperfusion with resin adsorption combined continuous veno-venous hemofiltration(HP+CWH) on plasm cytokines like TNF-α,IL-1β,IL-6,cellular immunity and prognosis in patients with multiple organ dysfunction syndrome(MODS).METHODS:This was a prospective,randomized clinical trial.A total of 30 patients who had been diagnosed with MODS were enrolled in this study.Patients were randomly allocated to routine treatment+HP+CWH group(treatment group) and routine treatment+only CWH group(control group).In the treatment group,patients received blood hemoperfusion with resin adsorption for 2hours,and then received CWH for 10 hours every day.In the control group,patients received CWH for 12 hours only every day.The patients in the two groups received blood purification therapy for three days.The plasma of patients in the treatment group was obtained at 0,2,12,24,26,36,48,50,60 hours,5th day,7th day and 10 th day,respectively.The plasma of patients in the control group was obtained at 0,12,24,36,48,60 hours,5th day,7th day and 10 th day,respectively.APACHE Ⅱscore,T-lymphocytes subpopulations,blood lactate acid concentration,heart rate,breathing rate,and oxygenation index were observed.RESULTS:Plasma cytokines like TNF-α,IL-1β,IL-6 decreased markedly after HP(P<0.01);T-lymphocytes subpopulations CD3+,CD4+,CD8+,CD4+/CD8+ increased after HP+CWH or only CWH.The plasma concentrations of TNF-α,IL-1β and IL-6 in the two groups were not markedly different at 12,36,and 50 hours.But on the 5th day,the plasma concentrations of TNF-α,IL-1β and IL-6 in the treatment group were lower than those in the control group(P<0.05).On the 28 th day,5patients died in the treatment group,and 6 patients in the control group.CONCLUSIONS:Both HP+CWH and CWH can clean plasma cytokines like TNF-α,IL-1β,and IL-6,and improve cellular immunity and clinical symptoms and signs of patients.Compared with only CWH,the plasma concentrations of TNF-α,IL-1β and IL-6 were lower on the 5th day,and patients have an increased survival rate on the 28 day in the HP+CWH group.

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.

Prolonged intestinal mucosal acidosis is associated with multiple organ failure in human acute pancreatitis: Gastric tonometry revisited

AIM： To evaluate whether multiple determinations of intramucosal pH （pHi） in acute pancreatitis （AP） patients could provide additional information of the disease severity during early hospitalization. METHODS： Twenty-one patients suffering from acute pancreatitis were monitored by gastric tonometry in the first 72 h after hospital admission. RESULTS： In the survivor group （n = 15） the initially low phi values returned to normal level （pHi ≥ 7.32） within 48 h （median pHi： d 1： 7.21; d 2： 7.32; d 3： 7.33）. In contrast, pHi values in the non-survivor group n = 6） were persistently either below or in the low normal range （median pHi 7.12; 7.12; 7.07 respectively）, but pHi differences between the two groups reached significance only after 24 h （P 〈 0.01）. Mucosal acidosis detected at any time during the monitored period was associated with the emergence of single or multiple organ dysfunction （P 〈 0.01）. CONCLUSION： Prolonged gastric mucosal acidosis was associated with remote organ dysfunction and failure in Acute Pancreatitis, however, correlation with the fatal outcome became significant only 24 h after admission. Due to its non-invasive nature gastric tonometry may supplement the pro-inflammatory markers to achieve a multi-faceted monitoring of the disease.

Low driving voltage in an organic light-emitting diode using MoO_3/NPB multiple quantum well structure in a hole transport layer

The driving voltage of an organic light-emitting diode（OLED） is lowered by employing molybdenum trioxide（MoO3）/N,N＇-bis（naphthalene-1-yl）-N,N＇-bis（phe-nyl）-benzidine（NPB） multiple quantum well（MQW） structure in the hole transport layer.For the device with double quantum well（DQW） structure of ITO/[MoO3（2.5 nm）/NPB（20 nm）]2/Alq3（50 nm）/LiF（0.8 nm）/Al（120 nm）],the turn-on voltage is reduced to 2.8 V,which is lowered by 0.4 V compared with that of the control device（without MQW structures）,and the driving voltage is 5.6 V,which is reduced by 1 V compared with that of the control device at the 1000 cd/m2.In this work,the enhancement of the injection and transport ability for holes could reduce the driving voltage for the device with MQW structure,which is attributed not only to the reduced energy barrier between ITO and NPB,but also to the forming charge transfer complex between MoO3 and NPB induced by the interfacial doping effect of MoO3.

Adult-onset Still's disease evolving with multiple organ failure and death:A case report and review of the literature

BACKGROUND Adult-onset Still’s disease(AOSD)is a rare systemic inflammatory disease,which is characterized by daily fever and arthritis,with an evanescent rash and neutrophilic leukocytosis.To date,there has been no definite laboratory or imaging test available for diagnosing AOSD;the diagnosis is one of exclusion,which can be very challenging.In particular,AOSD patients may experience different complications affecting their clinical picture,management,and prognosis.The treatment of AOSD remains largely empirical and involves therapeutic agents.CASE SUMMARY We report the case of a 36-year-old woman who presented with fever,red rash,arthralgia,and sore throat.Her serum ferritin level and white blood cell count were markedly elevated,and the first diagnosis 22 years prior was"juvenile rheumatoid arthritis of systemic type".The patient was treated with prednisone,sulfasalazine,methotrexate,and leflunomide.After remission of her symptoms,the patient stopped taking the medications,and the disease recurred.Ultimately,the patient was diagnosed with adult-onset Still's disease.Relapse occurred several times due to self-medication withdrawal,and an interleukin-6 antagonist(tocilizumab/Actemra)was administered to control the disease.Recently,she was hospitalized because an incision did not heal,and the patient suddenly developed high fever and diarrhea during hospitalization.The patient's disease progressed violently and quickly developed into macrophage activation syndrome,disseminated intravascular coagulation,shock,and multiple organ failure.The patient had sudden cardiac arrest,and she died despite emergency rescue efforts.CONCLUSION AOSD patients need regular follow-up in the long-term treatment process,and must press formulary standard medication,and do not voluntarily withdraw or reduce the dose.Otherwise it may cause disease back-and-forth or serious lifethreatening complications.Meanwhile,strict management of trauma,infections,tumors,and other diseases may contribute to improved outcomes in patients with complications.