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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Multiple organ dysfunction and rhabdomyolysis associated with moonwort poisoning: Report of four cases

BACKGROUND Moonwort is a widely used Chinese herbal medicine. It has various pharmacological effects, such as relieving cough and preventing asthma. To date,multiple organ dysfunction and rhabdomyolysis caused by moonwort poisoning have not been reported.CASE SUMMARY Here we report four cases of moonwort poisoning that presented with multiple organ dysfunction and rhabdomyolysis accompanied by vomiting, fatigue, and muscle aches. One patient was an adult male, two were adult females, and one was a boy, with an age range of 7–64 years. The adults were treated with hemoperfusion and symptomatic therapies, while the child was treated with plasma exchange and symptomatic therapies. All four patients recovered.CONCLUSION Blood purification combined with symptomatic treatment may be an effective method for managing multiple organ dysfunction and rhabdomyolysis caused by acute moonwort poisoning.

Multiple-Organ Extracorporeal Support Therapies in Critically Ill Patients

The critically ill patient is capable of presenting a multiple organ dysfunction syndrome (MODS) caused by different diseases, which can be infectious (sepsis, septic shock) as well as non-infectious (pancreatitis, large surgeries, traumatic injuries, burn patients and brain injuries), this syndrome is characterized by global hemodynamic and organ perfusion alterations accompanied by an uncontrolled and marked inflammatory response unresponsive to pharmacological treatment due to which extracorporeal organ support can be a viable option. Acute renal lesion can occur in up to 60% of patients receiving intensive care, and close to 10% - 20% require renal replacement therapy (RRT) globally this can be provided as peritoneal dialysis (PD) or intermittent hemodialysis (IHD), continuous renal replacement therapy (CRRT), hybrid therapies known as sustained slow efficiency dialysis (SLED), which combines the benefits IHD and CRRT, slow continuous ultrafiltration (SCUF). Extracorporeal membrane oxygenation (ECMO) and extracorporeal elimination of CO2, have been used more frequently lately, these are temporal artificial support used for respiratory and/or cardiac insufficiency that is refractory to conventional treatment. Acute liver failure in adults has a mortality rate close to 50% furthermore one-third of patients hospitalized for cirrhosis are likely to progress to acute liver failure which will drastically increase its mortality. Based on concepts of albumin dialysis, one of its most known is the following: Molecular Adsorbent Recirculating System (MARS), Fractionated Plasma Separation and Absorption—FPSA (Prometheus®) and also, hemoperfusion with different cartridges used in different extracorporeal therapies, used in liver failure, rhabdomyolysis, cytokine release syndrome and more in the context of the pandemic covid19. The objective of this review is to know the different extracorporeal therapies and the therapeutic utility in critical patients.

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.

Effects of Qingwen Baidu decoction on coagulation and multiple organ injury in rat models of sepsis

Background:Sepsis-induced coagulopathy and multiple organ dysfunction syndromes are the leading causes of death in patients with sepsis.Qingwen Baidu decoction(QWBD)can effectively improve the clinical manifestations of sepsis and ease inflammation,but its effects on coagulation functions and multiple organ injuries remain unclear.Methods:100 healthy,male Sprague-Dawley rats were randomly divided into the sham group,the cecal ligation and puncture(CLP)group,the low-dose QWBD group,and the high-dose QWBD group,with 25 rats in each group.The sepsis model was established using CLP.Blood was collected to measure platelet count,serum creatinine(Cr),blood urea nitrogen(BUN),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)levels,as well as coagulation function.The total protein in bronchoalveolar lavage fluid(BALF)was determined in each group of rats.The lung,liver,and kidney tissues were harvested,and statistics were calculated on the wet-to-dry(W/D)weight ratio.Changes in histopathology and thrombin level were evaluated in each group.The remaining ten rats in each group were observed daily to record the number of surviving rats.Such observation was made consecutively for 7 days to calculate survival rates.Results:After model establishment,ALT,AST,Cr,and BUN levels were significantly elevated(P<0.01).The BALF protein content and lung W/D weight ratio were significantly increased(P<0.01).Furthermore,the survival rate of rats was significantly reduced in the CLP group compared with the sham group.After the treatment,rats in the high-dose QWBD group had lower ALT(P<0.05),AST(P<0.01),Cr(P<0.05),BUN(P<0.01)levels,lower BALF protein content(P<0.05)and lower lung W/D weight ratio(P<0.01)than the CLP group.However,rats in the high-dose QWBD group had significantly better pathological changes in the lung,liver,and kidney compared to the sham group.After the treatment,the platelet level in the peripheral blood was elevated(P<0.05)and both activated partial thromboplastin time and prothrombin time were significantly shortened(P<0.01).The fibrinogen level was significantly increased(P<0.01).Finally,thrombin positive expression areas in the lung,liver,and kidney were significantly decreased in the high-dose QWBD group.Conclusion:QWBD can improve coagulation disorders caused by sepsis and has a protective effect on multiple organ injuries in rats.