Human herpesvirus 6(HHV-6)is a common childhood infection but rarely causes severe complications.In immunocompetent children,conditions such as febrile convulsions and roseola infantum are typical,with occasional seve...Human herpesvirus 6(HHV-6)is a common childhood infection but rarely causes severe complications.In immunocompetent children,conditions such as febrile convulsions and roseola infantum are typical,with occasional severe manifestations like meningoencephalitis and myocarditis.展开更多
This paper summarizes the nursing experience of a 65-year-old elderly patient with fulminant myocarditis complicated by cardiogenic shock who received veno-arterial extracorporeal membrane oxygenation(V-A ECMO)combine...This paper summarizes the nursing experience of a 65-year-old elderly patient with fulminant myocarditis complicated by cardiogenic shock who received veno-arterial extracorporeal membrane oxygenation(V-A ECMO)combined with intra-aortic balloon pump(IABP)support therapy.The core nursing measures included:establishing a multidisciplinary collaboration team to implement daily goal management;standardized anticoagulation monitoring;refined hemodynamic management;stepped respiratory support;and early rehabilitation intervention.After 9 days of ECMO support combined with 5 days of IABP support,the patient’s cardiac and respiratory functions recovered.The patient was discharged on the 42nd day and was fully recovered during the follow-up on the 60th day.This case suggests that refined nursing care for ECMO combined with IABP is the key to the treatment of fulminant myocarditis.展开更多
BACKGROUND Fulminant type 1 diabetes mellitus(FT1DM)that occurs during pregnancy or the perinatal period is known as pregnancy-related FT1DM(PF),always without history of abnormal glucose metabolism.Here,we present fo...BACKGROUND Fulminant type 1 diabetes mellitus(FT1DM)that occurs during pregnancy or the perinatal period is known as pregnancy-related FT1DM(PF),always without history of abnormal glucose metabolism.Here,we present four patients who developed FT1DM during treatment but were first diagnosed with gestational diabetes mellitus(GDM).CASE SUMMARY The clinical data of four patients with GDM combined with FT1DM admitted to our hospital between July 2018 and April 2021 were collected,and the patients and their infants were followed up.All patients were diagnosed with GDM during the second trimester and were treated.The blood glucose level elevated suddenly during the third trimester and then were diagnosed with FT1DM.Two patients had an insulin allergy,and two had symptoms of upper respiratory tract infection before onset.One patient developed ketoacidosis,and three developed ketosis.Two patients had cesarean section deliveries,and two had vaginal deliveries.The growth and development of the infants were normal.C-peptide levels were lower than those at onset,suggesting progressive impairment of islet function.The frequencies of the DRB109:01,DQB103:03,DQA103:02,DPA101:03,DPA102:02,DPB105:01,DRB401:03,G 01:01,and G 01:04 human leukocyte antigen(HLA)-G alleles were high in the present study.CONCLUSION In comparison with pregnancy-associated FT1DM(PF),patients with GDM combined with FT1DM had an older age of onset,higher body mass index,slower onset,fewer prodromal symptoms,and less acidosis.The pathogenesis may be due to various factors affecting the already fragileβ-cells of GDM patients with genetically susceptible class II HLA genotypes.We speculate that GDM combined with FT1DM during pregnancy,referred to as“double diabetes,”is a subtype of PF with its own unique characteristics that should be investigated further.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection often leads to pulmonary complications.Cardiovascular sequelae,including myocarditis and heart failure,have also been reported.Here,the study presen...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection often leads to pulmonary complications.Cardiovascular sequelae,including myocarditis and heart failure,have also been reported.Here,the study presents two fulminant myocarditis cases infected by SARS-CoV-2 exhibiting remarkable elevation of cardiac biomarkers without significant pulmonary injury,as determined by imaging examinations.Immunohistochemical staining reveals the viral antigen within cardiomyocytes,indicating that SARSCoV-2 could directly infect the myocardium.The full viral genomes from respiratory,anal,and myocardial specimens are obtained via next-generation sequencing.Phylogenetic analyses of the whole genome and spike gene indicate that viruses in the myocardium/pericardial effusion and anal swabs are closely related and cluster together yet diverge from those in the respiratory samples.In addition,unique mutations are found in the anal/myocardial strains compared to the respiratory strains,suggesting tissue-specific virus mutation and adaptation.These findings indicate genetically distinct SARS-CoV-2 variants have infiltrated and disseminated within myocardial tissues,independent of pulmonary injury,and point to different infection routes between the myocardium and respiratory tract,with myocardial infections potentially arising from intestinal infection.These findings highlight the potential for systemic SARS-CoV-2 infection and the importance of a thorough multi-organ assessment in patients for a comprehensive understanding of thepathogenesisof COVID-19.展开更多
The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA), also called ecstasy, is a neurotoxin widely consumed among young people that has increased in recent years because it is a recreational drug, of whi...The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA), also called ecstasy, is a neurotoxin widely consumed among young people that has increased in recent years because it is a recreational drug, of which immediate effects are known such as a greater sensation of well-being, extroversion, increased sensory perception. However, its long-term effects have been described very little in the medical literature, including damage to the heart, central nervous system, kidney, etc. One of its little-known effects is hepatotoxicity, of which few cases are known associated with fulminant hepatitis, which is a rapidly deteriorating condition that is generally associated with a syndrome of multiple organ dysfunction and death. Therefore, it is very important to know this type of damage in the short and long term. The following case is of a 39-year-old man who came to our service due to jaundice syndrome and the only history of MDMA consumption, who as the days went by met the criteria for fulminant liver failure, with damage to multiple organs (organ dysfunction syndrome).展开更多
Background Adult Fulminant myocarditis(FM)is the more serious form of acute myocarditis,and extracorporeal membrane oxygenation(ECMO)is an effective adjunction that helps to maintain circulation while providing adequa...Background Adult Fulminant myocarditis(FM)is the more serious form of acute myocarditis,and extracorporeal membrane oxygenation(ECMO)is an effective adjunction that helps to maintain circulation while providing adequate treatment.The blood supply of vital organs is guaranteed,which helps patients to survive the acute attack and improves the survival rate of FM.Methods In this study,50 clinical data of adult FM patients received in our hospital from July 2018 to July 2023 were collected for retrospective analysis.According to different treatment methods,they were divided into ECMO group(n=25)and non-ECMO group(n=25).After 14 days of treatment,the level of left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),creatine kinase isoenzymes(CK-MB),cardiac troponinⅠ(cTnⅠ)and brain natriuretic peptide(BNP),and the incidence of complications were compared between the two groups.Results Before treatment,there was no significant difference in cardiac function between the two groups(P>0.05).After 14 days of treatment,ECMO group showed greater decline than non-ECMO group in LVESD and LVEDD,and LVEF was higher than that in the non-ECMO group(P<0.05).The level of CK-MB,cTnⅠ and BNP in ECMO group were lower than those in non-ECMO(P<0.05).The overall incidence of complications was 8% in the ECMO group,which was lower than 32% in the non-ECMO group(P<0.05).Conclusions The early efficacy of ECMO treatment in adult patients with FM is considerable,which is conducive to improving the cardiac function of patients and preventing complications.展开更多
Background:Fulminant myocarditis(FM)is associated with high mortality and an unfavorable long-term prognosis.However,noninvasive,rapid diagnostic and monitoring methods for FM are lacking.Case summary:This report deta...Background:Fulminant myocarditis(FM)is associated with high mortality and an unfavorable long-term prognosis.However,noninvasive,rapid diagnostic and monitoring methods for FM are lacking.Case summary:This report details the case of a patient diagnosed with FM through a comprehensive assessment involving typical clinical symptoms,laboratory analyses,echocardiographic evidence,and cardiac magnetic resonance(CMR)findings.Before the patient underwent CMR,optical pumped magnetometer magnetocardiography(OPM-MCG)revealed abnormalities characteristic of substantial myocardial injury.After invasive coronary angiography,the patient’s coronary arteries were determined not to exhibit significant stenosis.Additionally,a myocardial bridge was observed in the middle segment of the anterior descending branch of the left coronary artery.Over a 7-month follow-up,the patient’s symptoms showed marked improvement,and the OPM-MCG eventually normalized,aligning with the findings indicated by the CMR.Conclusion:OPM-MCG is a valuable tool for therapy monitoring in FMs,offering a safe,non-invasive,and highly effective test for ancillary diagnostics and long-term prognostic follow-up.Additionally,MCG may potentially assist in clinical decision-making regarding the need for further interventions in patients with myocardial bridge.展开更多
AIM To evaluate the possibility of usingcultured human hepatocytes as a bridge betweenbioartificial liver and liver transplantation.METHODS In this experiment,the efficacy ofextracorporeal bioartificial liver support ...AIM To evaluate the possibility of usingcultured human hepatocytes as a bridge betweenbioartificial liver and liver transplantation.METHODS In this experiment,the efficacy ofextracorporeal bioartificial liver support system(EBLSS)consisting of spheriodal human livercells and cultured hepatocytes supernatant wasassessed in vivo using galactosamine inducedrabbit model of fulminant hepatic failure.RESULTS There was no difference of survivalbetween the two groups of rabbits,but in thesupported rabbits serum alanineaminotransferase,total bilirubin and creatininewere significantly lower and hepatocyte necrosiswas markedly milder than those in controlanimals.In addition,a good viability of humanliver cells was noted after the experiment.CONCLUSION EBLSS plays a biologic role inmaintaining and compensating the function ofthe liver.展开更多
AIM: To utilize transcatheter arterial steroid injection therapy (TASIT) via the hepatic artery to reduce hepatic macrophage activity in patients with severe acute hepatic failure.METHODS: Thirty-four patients with se...AIM: To utilize transcatheter arterial steroid injection therapy (TASIT) via the hepatic artery to reduce hepatic macrophage activity in patients with severe acute hepatic failure.METHODS: Thirty-four patients with severe acute hepatic failure were admitted to our hospital between June 2002 to June 2006 providing for the possibility of liver transplantation (LT). Seventeen patients were treated using traditional liver supportive procedures, and the other 17 patients additionally underwent TASIT with 1000 mg methylprednisolone per day for 3 continuous days. RESULTS: Of the 17 patients who received TASIT, 13 were cured without any complications, 2 died, and 2 underwent LT. Of the 17 patients who did not receive TASIT, 4 were self-limiting, 7 died, and 6 underwent LT. Univariate logistic analysis revealed that ascites, serum albumin, prothrombin time, platelet count, and TASIT were significant variables for predicating the prognosis. Multivariate logistic regression analysis using stepwise variable selection showed that prothrombin time, platelet count, and TASIT were independent predictive factors. CONCLUSION: TASIT might effectively prevent the progression of severe acute hepatic failure to a fatal stage of fulminant liver failure.展开更多
AIM： To study the effect of combined indwelling catheter, hemofiltration, respiration support and traditional Chinese medicine （e.g. Dahuang） in treating abdominal compartment syndrome of fulminant acute pancreatit...AIM： To study the effect of combined indwelling catheter, hemofiltration, respiration support and traditional Chinese medicine （e.g. Dahuang） in treating abdominal compartment syndrome of fulminant acute pancreatitis. METHODS： Patients with fulminant acute pancreatitis were divided randomly into 2 groups of combined indwelling catheter celiac drainage and intra-abdominal pressure monitoring and routine conservative measures group （group 1） and control group （group 2）. Routine non-operative conservative treatments including hemofiltration, respiration support, gastrointestinal TCM ablution were also applied in control group patients. Effectiveness of the two groups was observed, and APACHE Ⅱ scores were applied for analysis. RESULTS： On the second and fifth days after treatment, APACHE Ⅱ scores of group 1 and 2 patients were significantly different. Comparison of effectiveness （abdominalgia and burbulence relief time, hospitalization time） between groups 1 and 2 showed significant difference, as well as incidence rates of cysts formation. Mortality rates of groups 1 and 2 were 10.0% and 20.7%, respectively. For patients in group 1, celiac drainage quantity and intra-abdominal pressure, and hospitalization time were positively correlated （r = 0.552, 0.748, 0.923, P 〈 0.01） with APACHE Ⅱ scores. CONCLUSION： Combined indwelling catheter celiac drainage and intra-abdominal pressure monitoring, short veno-venous hemofiltration （SVVH）, gastrointestinal TCM ablution, respiration support have preventive and treatment effects on abdominal compartment syndrome of fulminant acute pancreatitis.展开更多
Intracranial hypertension is a major cause of morbidity and mortality of patients suffering from fulminant hepatic failure. The etiology of this intracranial hypertension is not fully determined, and is probably multi...Intracranial hypertension is a major cause of morbidity and mortality of patients suffering from fulminant hepatic failure. The etiology of this intracranial hypertension is not fully determined, and is probably multifactorial, combining a cytotoxic brain edema due to the astrocytic accumulation of glutamine, and an increase in cerebral blood volume and cerebral blood flow, in part due to inflammation, to glutamine and to toxic products of the diseased liver. Validated methods to control intracranial hypertension in fulminant hepatic failure patients mainly include mannitol, hypertonic saline, indomethacin, thiopental, and hyperventilation. However all these measures are often not sufficient in absence of liver transplantation, the only curative treatment of intracranial hypertension in fulminant hepatic failure to date. Induced moderate hypothermia seems very promising in this setting, but has to be validated by a controlled, randomized study. Artificial liver support systems have been under investigation for many decades. The bioartiflcial liver, based on both detoxification and swine liver cells, has shown some efficacy on reduction of intracranial pressure but did not show survival benefit in a controlled, randomized study. The Molecular Adsorbents Recirculating System has shown some efficacy in decreasing intracranial pressure in an animal model of liver failure, but has still to be evaluated in a phase Ⅲ trial.展开更多
AIM： To investigate the protective effect of stronger neo-minophafen C （SNMC） on fulminant hepatic failure （FHF） and its underlying mechanism. METHODS： A mouse model of FHF was established by intraperitoneal inj...AIM： To investigate the protective effect of stronger neo-minophafen C （SNMC） on fulminant hepatic failure （FHF） and its underlying mechanism. METHODS： A mouse model of FHF was established by intraperitoneal injection of galactosamine （D-Gal N） and lipopolysaccharide （LPS）. The survival rate, liver function, inflammatory factor and liver pathological change were obtained with and without SNMC treatment. Hepatoo/te survival was estimated by observing the stained mitochondria structure with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling （TUNEL） method and antibodies against cytochrome C （Cyt-C） and caspase-3. RESULTS： The levels of plasma tumor necrosis factor alpha （TNF-α）, nitric oxide （NO）, ET-1, interleukin-6 （IL-6）, and the degree of hepatic tissue injury were decreased in the SNMC-treated groups compared with those in the model group （P 〈 0.01）. However, there were no differences after different dosages administered at different time points. There was a significant difference in survival rates between the SNMC-treated groups and the model group （P 〈 0.01）. The apoptosis index was 32.3% at 6 h after a low dose of SNMC, which was considerably decreased from 32.3% ± 4.7% vs 5% ± 2.83% （P 〈 0.05） to 5% on d 7. The expression of Cyt-C and caspase-3 decreased with the prolongation of therapeutic time. Typical hepatocyte apoptosis was obviously ameliorated under electron microscope with the prolongation of therapeutic time. CONCLUSION： SNMC can effectively protect liver against FHF induced by LPS/D-Gal N. SNMC can prevent hepatocyte apoptosis by inhibiting inflammatory reaction and stabilizing mitochondria membrane to suppress the release of Cyt-C and sequent activation of caspase-3.展开更多
AIM： To investigate the clinical characteristics of fulminant hepatitis in pregnancy. METHODS： We compared and analyzed the etiology, clinical characteristics, and laboratory examinations of 25 cases of fulminant he...AIM： To investigate the clinical characteristics of fulminant hepatitis in pregnancy. METHODS： We compared and analyzed the etiology, clinical characteristics, and laboratory examinations of 25 cases of fulminant hepatitis in pregnancy and 30 cases of fulminant hepatitis not in pregnancy. RESULTS： HBV infection and chronic fulminant hepatitis were most common both in the pregnant and in the non-pregnant groups. Jaundice, digestive tract symptoms, increase of bilirubin and thrombinogen activity were the main manifestations. The incidence of hepatic encephalopathy （HE） and hepato-renal syndrome （HRS） was significantly different between the two groups. The incidence of preterm labor, dead fetus and neonatal asphyxia was high. CONCLUSION： Fulminant hepatitis is likely to occur in late pregnancy wibh more severe complications, which significantly influences maternity, perinatal fetus, and newborn.展开更多
AIM: To explore the alterations of intestinal mucosa morphology, and the effects of tumor necrosis factor a (TNFα) on enterocyte apoptosis in mice with fulminant hepatic failure (FHF). METHODS: Liver damage was induc...AIM: To explore the alterations of intestinal mucosa morphology, and the effects of tumor necrosis factor a (TNFα) on enterocyte apoptosis in mice with fulminant hepatic failure (FHF). METHODS: Liver damage was induced by lipopolysaccharide (LPS)/TNF-α in D-galactosamine (GaIN) sensitized BALB/c mice. There were 40 mice in normal saline (NS)-treated group, 40 mice in LPS-treated group, 40 mice in GaIN-treated group, 120 mice in GaIN/ LPS-treated group and 120 mice in GaIN/ TNFα-treated group. Each group was divided into five subgroups of eight mice each. Serum samples and liver, intestinal tissues were respectively obtained at 2, 6,9,12 and 24 h after administration. Anti-TNFa monoclonal antibody was injected intravenously into GaIN/LPS-treated mice. Serum TNFα levels were determined by enzyme linked immunosorbent assays (ELISA). Serum ALT levels were determined using an automatic analyzer. The intestinal tissues were studied under light microscope and electron microscope at 2, 6, 9,12 and 24 h in mice with fulminant hepatic failure, respectively. Enterocyte apoptosis was determined by terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) method. The expression of tumor necrosis factor receptor 1 (TNFR1) in intestinal tissue was tested by immunohistochemistry Envision Two Steps. RESULTS: Gut mucosa was morphologically normal at all time points in all groups, but typical apoptotic cells could be seen in all experimental groups under electron microscope. Apoptosis rate of gut mucosal epithelial cells were significantly increased at 6, 9 and 12 h, peaked at 12 h in mice with fulminant hepatic failure. TNFa induced apoptosis of enterocytes in mice with FHF. The integrated OD (IOD) levels of TNFa receptor 1 protein expressed in the intestine of mice with GaIN/LPS and GaIN/ TNFα induced FHF at 2, 6, 9, 12 and 24 h after GaIN/LPS and GaIN/TNFα administration were 169.54±52.62/905.79±111.84,11 350.67±2 133.26/28 160.37±4 601.67, 25 781.00±2 277.75/122 352.30±49 412.40, 5 241.53±3 007.24/ 49 157.93±9 804.88, 7 086.13±1 031.15/3 283.45±127.67, respectively, compared with those in control groups (with NS, LPS and GaIN administration, respectively). IOD level of TNFR1 changed significantly at 6, 9 and 12 h after GaIN/LPS and GalN/TNFa administration. The expression of TNFR1 protein was significantly higher at 9 h after GaIN/LPS and GaIN/TNFα administration than that in control groups. Protein expression of TNFR1 was positively correlated with enterocyte apoptosis. CONCLUSION: TNFα can induce apoptosis of enterocytes in mice with FHF. Anti-TNFα IgG can inhibit this role.展开更多
AIM: To investigate the pathogenic role of cathepsin B and the protective effect of a cathepsin B inhibitor (CA074Me) in fulminant hepatic failure in mice. METHODS: LPS/D-Gal N was injected into mice of the model grou...AIM: To investigate the pathogenic role of cathepsin B and the protective effect of a cathepsin B inhibitor (CA074Me) in fulminant hepatic failure in mice. METHODS: LPS/D-Gal N was injected into mice of the model group to induce fulminant hepatic failure; the protected group was administered CA-074me for 30 min before LPS/D-Gal N treatment; the normal group was given isochoric physiologic saline. Liver tissue histopathology was determined with HE at 2, 4, 6 and 8 h after Lps/D-Gal injection. Hepatocyte apoptosis was examined by TUNEL method. The expression of cathepsin B in liver tissues was investigated by immunohistochemistry, Western blot and RT-PCR. RESULTS: Compared with the normal group, massive typical hepatocyte apoptosis occurred in the model group; the number of apoptotic cells reached a maximum 6 h after injection. The apoptosis index (AI) in the protected group was clearly reduced (30.4 ± 2.8 vs 18.1 ± 2.0, P < 0.01 ). Cathepsin B activity was markedly increased in drug-treated mice compared with the normal group (P < 0.01). Incubation with LPS/D-Gal N at selected time points resulted in a timedependent increase in cathepsin B activity, and reached a maximum by 8 h. The expression of cathepsin B was significantly decreased in the protected group (P < 0.01). CONCLUSION: Cathepsin B plays an essential role in the pathogenesis of fulminant hepatic failure, and the cathepsin B inhibitor CA-074me can attenuate apoptosis and liver injury.展开更多
BACKGROUND Heterogeneous macrophages play an important role in multiple liver diseases,including viral fulminant hepatitis(VFH).Fibrinogen-like protein 2(FGL2)is expressed on macrophages and regulates VFH pathogenesis...BACKGROUND Heterogeneous macrophages play an important role in multiple liver diseases,including viral fulminant hepatitis(VFH).Fibrinogen-like protein 2(FGL2)is expressed on macrophages and regulates VFH pathogenesis;however,the underlying mechanism remains unclear.AIM To explore how FGL2 regulates macrophage function and subsequent liver injury during VFH.METHODS Murine hepatitis virus strain 3(MHV-3)was used to induce VFH in FGL2-deficient(Fgl2-/-)and wild-type(WT)mice.The dynamic constitution of hepatic macrophages was examined.Adoptive transfer of Fgl2-/-or WT bone marrowderived macrophages(BMDMs)into WT recipients with macrophages depleted prior to infection was carried out and the consequent degree of liver damage was compared.The signaling cascades that may be regulated by FGL2 were detected in macrophages.RESULTS Following MHV-3 infection,hepatic macrophages were largely replenished by proinflammatory monocyte-derived macrophages(MoMFs),which expressed high levels of FGL2.In Fgl2-/-mice,the number of infiltrating inflammatory MoMFs was reduced compared with that in WT mice after viral infection.Macrophage depletion ameliorated liver damage in WT mice and further alleviated liver damage in Fgl2-/-mice.Adoptive transfer of Fgl2-/-BMDMs into macrophage-removed recipients significantly reduced the degree of liver damage.Inhibition of monocyte infiltration also significantly ameliorated liver damage.Functionally,Fgl2 deletion impaired macrophage phagocytosis and the antigen presentation potential and attenuated the proinflammatory phenotype.At the molecular level,FGL2 deficiency impaired IRF3,IRF7,and p38 phosphorylation,along with NF-κB activation in BMDMs in response to viral infection.CONCLUSION Infiltrated MoMFs represent a major source of hepatic inflammation during VFH progression,and FGL2 expression on MoMFs maintains the proinflammatory phenotype via p38-dependent positive feedback,contributing to VFH pathogenesis.展开更多
AIM： To delineate the mechanisms of renal vasoconstriction in hepatorenal syndrome （HRS）, we investigated the expression of type I inositol 1, 4, 5-triphosphate receptors （IP3R I） of kidney in mice with fulminant...AIM： To delineate the mechanisms of renal vasoconstriction in hepatorenal syndrome （HRS）, we investigated the expression of type I inositol 1, 4, 5-triphosphate receptors （IP3R I） of kidney in mice with fulminant hepatic failure （FHF）. METHODS： FHF was induced by lipopolysaccharide （LPS） in D-galactosamine （GAIN） sensitized BALB/c mice. There were 20 mice in normal saline （NS）-treated group, 20 mice in LPS-treated group, 20 mice in GaIN- treated group, and 60 mice in GalN/LPS-treated group （FHF group）. Liver and kidney tissues were obtained at 2, 6, and 9 h after administration. The liver and kidney specimens were stained with hematoxylin-eosin for studying morphological changes under light microscope. The expression of IP3R I in kidney tissue was tested by immunohistochemistry, Western blot and reverse transcription （RT）-PCR. RESULTS： Kidney tissues were morphologically normal at all time points in all groups. IP3R I proteins were found localized in the plasma region of glomerular mesangial cells （GMC） and vascular smooth muscle cells （VSMC） in kidney by immunohistochemical staining. In kidney of mice with FHF at 6 h and 9 h IP3R I staining was upregulated. Results from Western blot demonstrated consistent and significant increment of IP3R I expression in mice with FHF at 6 h and 9 h （t = 3.16, P 〈 0.05; t = 5.43, P 〈 0.01）. Furthermore, we evaluated IP3R I mRNA expression by RT-PCR and observed marked upregulation of IP3R I mRNA in FHF samples at 2 h, 6 h and 9 h compared to controls （t = 2.97, P 〈 0.05; t = 4.42, P 〈 0.01; t = 3.81, P 〈 0.01）. CONCLUSION： The expression of IP3R I protein increased in GMC and renal VSMC of mice with FHF, possibly caused by up-regulation of IP3R I mRNA.展开更多
AIM: To examine if fulminant Clostridium difficile infections(CDI) resulting in colectomy was associated with a prior appendectomy and whether any association affected the severity of the disease.METHODS: A retrospect...AIM: To examine if fulminant Clostridium difficile infections(CDI) resulting in colectomy was associated with a prior appendectomy and whether any association affected the severity of the disease.METHODS: A retrospective chart review was performed on patients who underwent colectomy for CDI between 2001 and 2011.The appendectomy rate was calculated based on the absence of an appendix on the surgical pathology report.This was compared to an established lifetime risk of appendectomy in the general population.A chart review was performed for mortality and traditional markers of CDI disease severity.Fisher’s exact test was used to calculate the likelihood of association between prior appendectomy,mortality,and clinical markers of severity of infection.RESULTS: Fifty-five specimens were identified with pseudomembranous colitis consistent with CDI.All patients had a clinical history consistent with CDI and 45 of 55(81.8%) specimens also had microbiological confirmation of CDI.Appendectomy was observed in 24 of 55 specimens(0.436,99%CI: 0.280-0.606).This was compared to the lifetime incidence of appendectomy of 17.6%.The rate of appendectomy in our sample was significantly higher than would be expected in the general population(43.6% vs 17.6%,P 【 0.01).Disease severity did not differ based on presence or absence of an appendix and no association was detected between prior appendectomy and mortality(OR = 0.588,95%CI: 0.174-1.970).CONCLUSION: The rate of appendectomy in the patients whose CDI led to colectomy,was significantly higher than the calculated lifetime risk,suggesting an association of appendectomy and severe CDI resulting in colectomy.Larger prospective studies are needed to assess any potential causal relationships affecting fulminant CDI.展开更多
AIM:To establish an appropriate primate model of fulminant hepatic failure (FHF).METHODS:We have,for the first time,established a large animal model of FHF in Macaca mulatta by intraperitoneal infusion of amatoxin and...AIM:To establish an appropriate primate model of fulminant hepatic failure (FHF).METHODS:We have,for the first time,established a large animal model of FHF in Macaca mulatta by intraperitoneal infusion of amatoxin and endotoxin.Clinical features,biochemical indexes,histopathology and iconography were examined to dynamically investigate the progress and outcome of the animal model.RESULTS:Our results showed that the enzymes and serum bilirubin were markedly increased and the enzyme-bilirubin segregation emerged 36 h after toxin administration.Coagulation activity was significantly decreased.Gradually deteriorated parenchymal abnormality was detected by magnetic resonance imaging (MRI) and ultrasonography at 48 h.The liver biopsy showed marked hepatocyte steatosis and massive parenchymal necrosis at 36 h and 49 h,respectively.The autopsy showed typical yellow atrophy of the liver.Hepatic encephalopathy of the models was also confirmed by hepatic coma,MRI and pathological changes of cerebral edema.The lethal effects of the extrahepatic organ dysfunction were ruled out by their biochemical indices,imaging and histopathology.CONCLUSION:We have established an appropriate large primate model of FHF,which is closely similar to clinic cases,and can be used for investigation of the mechanism of FHF and for evaluation of potential medical therapies.展开更多
BACKGROUND: Fulminant hepatic failure (FHF) is not uncommon in our clinical practice in Bangladesh. There was a rise in acute hepatitis E virus (HEV) in Bangladesh after the 2004 floods. At that time, most of the coun...BACKGROUND: Fulminant hepatic failure (FHF) is not uncommon in our clinical practice in Bangladesh. There was a rise in acute hepatitis E virus (HEV) in Bangladesh after the 2004 floods. At that time, most of the country was under water for more than a month, leading to sewage contamination of the water supply. The aim of this study was to investigate the etiology of FHF in Bangladesh. METHODS: In this retrospective study, 23 patients with FHF who presented with severe impairment of hepato- cellular function (i.e. encephalopathy, coagulopathy and jaundice) within 6 months of onset of symptoms were included. There were 17 men and 6 women, aged from 18 to 32 years. Four of the women were pregnant. Patients were tested for markers for common hepatotrophic viruses. A relevant history was taken and the Patient Record Book of the Unit was reviewed. RESULTS: 56.52% patients (13/23) had HEV infection, and all were anti-HEV IgM-positive tested by ELISA. HBV infection was detected in 34.78% patients (8/23), all of whom were tested positive for either HBsAg or anti-HBs IgM by ELISA. 8.7% patients (2/23) had a positive history for intake of alcohol and/or drugs. CONCLUSIONS: Acute HEV infection is the leading cause of FHF in Bangladesh. Sewage contamination of the water supply following floods contributes to a higher incidence of HEV infection. HBV infection is also important.展开更多
文摘Human herpesvirus 6(HHV-6)is a common childhood infection but rarely causes severe complications.In immunocompetent children,conditions such as febrile convulsions and roseola infantum are typical,with occasional severe manifestations like meningoencephalitis and myocarditis.
文摘This paper summarizes the nursing experience of a 65-year-old elderly patient with fulminant myocarditis complicated by cardiogenic shock who received veno-arterial extracorporeal membrane oxygenation(V-A ECMO)combined with intra-aortic balloon pump(IABP)support therapy.The core nursing measures included:establishing a multidisciplinary collaboration team to implement daily goal management;standardized anticoagulation monitoring;refined hemodynamic management;stepped respiratory support;and early rehabilitation intervention.After 9 days of ECMO support combined with 5 days of IABP support,the patient’s cardiac and respiratory functions recovered.The patient was discharged on the 42nd day and was fully recovered during the follow-up on the 60th day.This case suggests that refined nursing care for ECMO combined with IABP is the key to the treatment of fulminant myocarditis.
基金Supported by National Natural Science Foundation of China,No.82270864.
文摘BACKGROUND Fulminant type 1 diabetes mellitus(FT1DM)that occurs during pregnancy or the perinatal period is known as pregnancy-related FT1DM(PF),always without history of abnormal glucose metabolism.Here,we present four patients who developed FT1DM during treatment but were first diagnosed with gestational diabetes mellitus(GDM).CASE SUMMARY The clinical data of four patients with GDM combined with FT1DM admitted to our hospital between July 2018 and April 2021 were collected,and the patients and their infants were followed up.All patients were diagnosed with GDM during the second trimester and were treated.The blood glucose level elevated suddenly during the third trimester and then were diagnosed with FT1DM.Two patients had an insulin allergy,and two had symptoms of upper respiratory tract infection before onset.One patient developed ketoacidosis,and three developed ketosis.Two patients had cesarean section deliveries,and two had vaginal deliveries.The growth and development of the infants were normal.C-peptide levels were lower than those at onset,suggesting progressive impairment of islet function.The frequencies of the DRB109:01,DQB103:03,DQA103:02,DPA101:03,DPA102:02,DPB105:01,DRB401:03,G 01:01,and G 01:04 human leukocyte antigen(HLA)-G alleles were high in the present study.CONCLUSION In comparison with pregnancy-associated FT1DM(PF),patients with GDM combined with FT1DM had an older age of onset,higher body mass index,slower onset,fewer prodromal symptoms,and less acidosis.The pathogenesis may be due to various factors affecting the already fragileβ-cells of GDM patients with genetically susceptible class II HLA genotypes.We speculate that GDM combined with FT1DM during pregnancy,referred to as“double diabetes,”is a subtype of PF with its own unique characteristics that should be investigated further.
基金supported by the National Key R&D Program of China(2023YFC2307500 and 2021YFC2701700)National Natural Science Foundation of China(82341115)+5 种基金Beijing Research Center for Respiratory Infectious Diseases(BJRID2024-003)Major Project of Guangzhou National Laboratory(GZNL2023A01001 and SRPG22-001)the National Science and Technology Infrastructure of China(National Pathogen Resource Center-NPRC-32)Y.B.is supported by the Youth Innovation Promotion Association of CAs(Y2021034)CAS Project for Young Scientists in Basic Research(YSBR-086)the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202208).
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection often leads to pulmonary complications.Cardiovascular sequelae,including myocarditis and heart failure,have also been reported.Here,the study presents two fulminant myocarditis cases infected by SARS-CoV-2 exhibiting remarkable elevation of cardiac biomarkers without significant pulmonary injury,as determined by imaging examinations.Immunohistochemical staining reveals the viral antigen within cardiomyocytes,indicating that SARSCoV-2 could directly infect the myocardium.The full viral genomes from respiratory,anal,and myocardial specimens are obtained via next-generation sequencing.Phylogenetic analyses of the whole genome and spike gene indicate that viruses in the myocardium/pericardial effusion and anal swabs are closely related and cluster together yet diverge from those in the respiratory samples.In addition,unique mutations are found in the anal/myocardial strains compared to the respiratory strains,suggesting tissue-specific virus mutation and adaptation.These findings indicate genetically distinct SARS-CoV-2 variants have infiltrated and disseminated within myocardial tissues,independent of pulmonary injury,and point to different infection routes between the myocardium and respiratory tract,with myocardial infections potentially arising from intestinal infection.These findings highlight the potential for systemic SARS-CoV-2 infection and the importance of a thorough multi-organ assessment in patients for a comprehensive understanding of thepathogenesisof COVID-19.
文摘The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA), also called ecstasy, is a neurotoxin widely consumed among young people that has increased in recent years because it is a recreational drug, of which immediate effects are known such as a greater sensation of well-being, extroversion, increased sensory perception. However, its long-term effects have been described very little in the medical literature, including damage to the heart, central nervous system, kidney, etc. One of its little-known effects is hepatotoxicity, of which few cases are known associated with fulminant hepatitis, which is a rapidly deteriorating condition that is generally associated with a syndrome of multiple organ dysfunction and death. Therefore, it is very important to know this type of damage in the short and long term. The following case is of a 39-year-old man who came to our service due to jaundice syndrome and the only history of MDMA consumption, who as the days went by met the criteria for fulminant liver failure, with damage to multiple organs (organ dysfunction syndrome).
基金supported by the Natural Science Foundation of Hunan Province,China(No.2021JJ40505/No.2021JJ30619/No.2020JJ8002)the Scientific Research Project of Hunan Provincial Health Commission(No.202210004450)。
文摘Background Adult Fulminant myocarditis(FM)is the more serious form of acute myocarditis,and extracorporeal membrane oxygenation(ECMO)is an effective adjunction that helps to maintain circulation while providing adequate treatment.The blood supply of vital organs is guaranteed,which helps patients to survive the acute attack and improves the survival rate of FM.Methods In this study,50 clinical data of adult FM patients received in our hospital from July 2018 to July 2023 were collected for retrospective analysis.According to different treatment methods,they were divided into ECMO group(n=25)and non-ECMO group(n=25).After 14 days of treatment,the level of left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),creatine kinase isoenzymes(CK-MB),cardiac troponinⅠ(cTnⅠ)and brain natriuretic peptide(BNP),and the incidence of complications were compared between the two groups.Results Before treatment,there was no significant difference in cardiac function between the two groups(P>0.05).After 14 days of treatment,ECMO group showed greater decline than non-ECMO group in LVESD and LVEDD,and LVEF was higher than that in the non-ECMO group(P<0.05).The level of CK-MB,cTnⅠ and BNP in ECMO group were lower than those in non-ECMO(P<0.05).The overall incidence of complications was 8% in the ECMO group,which was lower than 32% in the non-ECMO group(P<0.05).Conclusions The early efficacy of ECMO treatment in adult patients with FM is considerable,which is conducive to improving the cardiac function of patients and preventing complications.
基金supported by Sponsored by Beijing Nova Program(20220484222)‘Deng Feng’Training Program(DFL20220603)Project of The Beijing Lab for Cardiovascular Precision Medicine(PXM2018_014226_000013).
文摘Background:Fulminant myocarditis(FM)is associated with high mortality and an unfavorable long-term prognosis.However,noninvasive,rapid diagnostic and monitoring methods for FM are lacking.Case summary:This report details the case of a patient diagnosed with FM through a comprehensive assessment involving typical clinical symptoms,laboratory analyses,echocardiographic evidence,and cardiac magnetic resonance(CMR)findings.Before the patient underwent CMR,optical pumped magnetometer magnetocardiography(OPM-MCG)revealed abnormalities characteristic of substantial myocardial injury.After invasive coronary angiography,the patient’s coronary arteries were determined not to exhibit significant stenosis.Additionally,a myocardial bridge was observed in the middle segment of the anterior descending branch of the left coronary artery.Over a 7-month follow-up,the patient’s symptoms showed marked improvement,and the OPM-MCG eventually normalized,aligning with the findings indicated by the CMR.Conclusion:OPM-MCG is a valuable tool for therapy monitoring in FMs,offering a safe,non-invasive,and highly effective test for ancillary diagnostics and long-term prognostic follow-up.Additionally,MCG may potentially assist in clinical decision-making regarding the need for further interventions in patients with myocardial bridge.
基金the national key project fund of the"9th Five Year Plan",No.96-920-12-02
文摘AIM To evaluate the possibility of usingcultured human hepatocytes as a bridge betweenbioartificial liver and liver transplantation.METHODS In this experiment,the efficacy ofextracorporeal bioartificial liver support system(EBLSS)consisting of spheriodal human livercells and cultured hepatocytes supernatant wasassessed in vivo using galactosamine inducedrabbit model of fulminant hepatic failure.RESULTS There was no difference of survivalbetween the two groups of rabbits,but in thesupported rabbits serum alanineaminotransferase,total bilirubin and creatininewere significantly lower and hepatocyte necrosiswas markedly milder than those in controlanimals.In addition,a good viability of humanliver cells was noted after the experiment.CONCLUSION EBLSS plays a biologic role inmaintaining and compensating the function ofthe liver.
文摘AIM: To utilize transcatheter arterial steroid injection therapy (TASIT) via the hepatic artery to reduce hepatic macrophage activity in patients with severe acute hepatic failure.METHODS: Thirty-four patients with severe acute hepatic failure were admitted to our hospital between June 2002 to June 2006 providing for the possibility of liver transplantation (LT). Seventeen patients were treated using traditional liver supportive procedures, and the other 17 patients additionally underwent TASIT with 1000 mg methylprednisolone per day for 3 continuous days. RESULTS: Of the 17 patients who received TASIT, 13 were cured without any complications, 2 died, and 2 underwent LT. Of the 17 patients who did not receive TASIT, 4 were self-limiting, 7 died, and 6 underwent LT. Univariate logistic analysis revealed that ascites, serum albumin, prothrombin time, platelet count, and TASIT were significant variables for predicating the prognosis. Multivariate logistic regression analysis using stepwise variable selection showed that prothrombin time, platelet count, and TASIT were independent predictive factors. CONCLUSION: TASIT might effectively prevent the progression of severe acute hepatic failure to a fatal stage of fulminant liver failure.
文摘AIM： To study the effect of combined indwelling catheter, hemofiltration, respiration support and traditional Chinese medicine （e.g. Dahuang） in treating abdominal compartment syndrome of fulminant acute pancreatitis. METHODS： Patients with fulminant acute pancreatitis were divided randomly into 2 groups of combined indwelling catheter celiac drainage and intra-abdominal pressure monitoring and routine conservative measures group （group 1） and control group （group 2）. Routine non-operative conservative treatments including hemofiltration, respiration support, gastrointestinal TCM ablution were also applied in control group patients. Effectiveness of the two groups was observed, and APACHE Ⅱ scores were applied for analysis. RESULTS： On the second and fifth days after treatment, APACHE Ⅱ scores of group 1 and 2 patients were significantly different. Comparison of effectiveness （abdominalgia and burbulence relief time, hospitalization time） between groups 1 and 2 showed significant difference, as well as incidence rates of cysts formation. Mortality rates of groups 1 and 2 were 10.0% and 20.7%, respectively. For patients in group 1, celiac drainage quantity and intra-abdominal pressure, and hospitalization time were positively correlated （r = 0.552, 0.748, 0.923, P 〈 0.01） with APACHE Ⅱ scores. CONCLUSION： Combined indwelling catheter celiac drainage and intra-abdominal pressure monitoring, short veno-venous hemofiltration （SVVH）, gastrointestinal TCM ablution, respiration support have preventive and treatment effects on abdominal compartment syndrome of fulminant acute pancreatitis.
文摘Intracranial hypertension is a major cause of morbidity and mortality of patients suffering from fulminant hepatic failure. The etiology of this intracranial hypertension is not fully determined, and is probably multifactorial, combining a cytotoxic brain edema due to the astrocytic accumulation of glutamine, and an increase in cerebral blood volume and cerebral blood flow, in part due to inflammation, to glutamine and to toxic products of the diseased liver. Validated methods to control intracranial hypertension in fulminant hepatic failure patients mainly include mannitol, hypertonic saline, indomethacin, thiopental, and hyperventilation. However all these measures are often not sufficient in absence of liver transplantation, the only curative treatment of intracranial hypertension in fulminant hepatic failure to date. Induced moderate hypothermia seems very promising in this setting, but has to be validated by a controlled, randomized study. Artificial liver support systems have been under investigation for many decades. The bioartiflcial liver, based on both detoxification and swine liver cells, has shown some efficacy on reduction of intracranial pressure but did not show survival benefit in a controlled, randomized study. The Molecular Adsorbents Recirculating System has shown some efficacy in decreasing intracranial pressure in an animal model of liver failure, but has still to be evaluated in a phase Ⅲ trial.
基金Supported by the Key Program During the Tenth Five-Year Plan of HeilongJiang Province, No. 200101031-00
文摘AIM： To investigate the protective effect of stronger neo-minophafen C （SNMC） on fulminant hepatic failure （FHF） and its underlying mechanism. METHODS： A mouse model of FHF was established by intraperitoneal injection of galactosamine （D-Gal N） and lipopolysaccharide （LPS）. The survival rate, liver function, inflammatory factor and liver pathological change were obtained with and without SNMC treatment. Hepatoo/te survival was estimated by observing the stained mitochondria structure with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling （TUNEL） method and antibodies against cytochrome C （Cyt-C） and caspase-3. RESULTS： The levels of plasma tumor necrosis factor alpha （TNF-α）, nitric oxide （NO）, ET-1, interleukin-6 （IL-6）, and the degree of hepatic tissue injury were decreased in the SNMC-treated groups compared with those in the model group （P 〈 0.01）. However, there were no differences after different dosages administered at different time points. There was a significant difference in survival rates between the SNMC-treated groups and the model group （P 〈 0.01）. The apoptosis index was 32.3% at 6 h after a low dose of SNMC, which was considerably decreased from 32.3% ± 4.7% vs 5% ± 2.83% （P 〈 0.05） to 5% on d 7. The expression of Cyt-C and caspase-3 decreased with the prolongation of therapeutic time. Typical hepatocyte apoptosis was obviously ameliorated under electron microscope with the prolongation of therapeutic time. CONCLUSION： SNMC can effectively protect liver against FHF induced by LPS/D-Gal N. SNMC can prevent hepatocyte apoptosis by inhibiting inflammatory reaction and stabilizing mitochondria membrane to suppress the release of Cyt-C and sequent activation of caspase-3.
文摘AIM： To investigate the clinical characteristics of fulminant hepatitis in pregnancy. METHODS： We compared and analyzed the etiology, clinical characteristics, and laboratory examinations of 25 cases of fulminant hepatitis in pregnancy and 30 cases of fulminant hepatitis not in pregnancy. RESULTS： HBV infection and chronic fulminant hepatitis were most common both in the pregnant and in the non-pregnant groups. Jaundice, digestive tract symptoms, increase of bilirubin and thrombinogen activity were the main manifestations. The incidence of hepatic encephalopathy （HE） and hepato-renal syndrome （HRS） was significantly different between the two groups. The incidence of preterm labor, dead fetus and neonatal asphyxia was high. CONCLUSION： Fulminant hepatitis is likely to occur in late pregnancy wibh more severe complications, which significantly influences maternity, perinatal fetus, and newborn.
基金Supported by Research Foundation of Ministry of Public Health, No. 97100252
文摘AIM: To explore the alterations of intestinal mucosa morphology, and the effects of tumor necrosis factor a (TNFα) on enterocyte apoptosis in mice with fulminant hepatic failure (FHF). METHODS: Liver damage was induced by lipopolysaccharide (LPS)/TNF-α in D-galactosamine (GaIN) sensitized BALB/c mice. There were 40 mice in normal saline (NS)-treated group, 40 mice in LPS-treated group, 40 mice in GaIN-treated group, 120 mice in GaIN/ LPS-treated group and 120 mice in GaIN/ TNFα-treated group. Each group was divided into five subgroups of eight mice each. Serum samples and liver, intestinal tissues were respectively obtained at 2, 6,9,12 and 24 h after administration. Anti-TNFa monoclonal antibody was injected intravenously into GaIN/LPS-treated mice. Serum TNFα levels were determined by enzyme linked immunosorbent assays (ELISA). Serum ALT levels were determined using an automatic analyzer. The intestinal tissues were studied under light microscope and electron microscope at 2, 6, 9,12 and 24 h in mice with fulminant hepatic failure, respectively. Enterocyte apoptosis was determined by terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) method. The expression of tumor necrosis factor receptor 1 (TNFR1) in intestinal tissue was tested by immunohistochemistry Envision Two Steps. RESULTS: Gut mucosa was morphologically normal at all time points in all groups, but typical apoptotic cells could be seen in all experimental groups under electron microscope. Apoptosis rate of gut mucosal epithelial cells were significantly increased at 6, 9 and 12 h, peaked at 12 h in mice with fulminant hepatic failure. TNFa induced apoptosis of enterocytes in mice with FHF. The integrated OD (IOD) levels of TNFa receptor 1 protein expressed in the intestine of mice with GaIN/LPS and GaIN/ TNFα induced FHF at 2, 6, 9, 12 and 24 h after GaIN/LPS and GaIN/TNFα administration were 169.54±52.62/905.79±111.84,11 350.67±2 133.26/28 160.37±4 601.67, 25 781.00±2 277.75/122 352.30±49 412.40, 5 241.53±3 007.24/ 49 157.93±9 804.88, 7 086.13±1 031.15/3 283.45±127.67, respectively, compared with those in control groups (with NS, LPS and GaIN administration, respectively). IOD level of TNFR1 changed significantly at 6, 9 and 12 h after GaIN/LPS and GalN/TNFa administration. The expression of TNFR1 protein was significantly higher at 9 h after GaIN/LPS and GaIN/TNFα administration than that in control groups. Protein expression of TNFR1 was positively correlated with enterocyte apoptosis. CONCLUSION: TNFα can induce apoptosis of enterocytes in mice with FHF. Anti-TNFα IgG can inhibit this role.
基金Supported by(in part)A grant from the China Postdoctoral Science Foundation
文摘AIM: To investigate the pathogenic role of cathepsin B and the protective effect of a cathepsin B inhibitor (CA074Me) in fulminant hepatic failure in mice. METHODS: LPS/D-Gal N was injected into mice of the model group to induce fulminant hepatic failure; the protected group was administered CA-074me for 30 min before LPS/D-Gal N treatment; the normal group was given isochoric physiologic saline. Liver tissue histopathology was determined with HE at 2, 4, 6 and 8 h after Lps/D-Gal injection. Hepatocyte apoptosis was examined by TUNEL method. The expression of cathepsin B in liver tissues was investigated by immunohistochemistry, Western blot and RT-PCR. RESULTS: Compared with the normal group, massive typical hepatocyte apoptosis occurred in the model group; the number of apoptotic cells reached a maximum 6 h after injection. The apoptosis index (AI) in the protected group was clearly reduced (30.4 ± 2.8 vs 18.1 ± 2.0, P < 0.01 ). Cathepsin B activity was markedly increased in drug-treated mice compared with the normal group (P < 0.01). Incubation with LPS/D-Gal N at selected time points resulted in a timedependent increase in cathepsin B activity, and reached a maximum by 8 h. The expression of cathepsin B was significantly decreased in the protected group (P < 0.01). CONCLUSION: Cathepsin B plays an essential role in the pathogenesis of fulminant hepatic failure, and the cathepsin B inhibitor CA-074me can attenuate apoptosis and liver injury.
基金Supported by the National Science and Technology Major Project,No.2017ZX10202201and the National Natural Science Foundation of China,No.NSFC 81700529。
文摘BACKGROUND Heterogeneous macrophages play an important role in multiple liver diseases,including viral fulminant hepatitis(VFH).Fibrinogen-like protein 2(FGL2)is expressed on macrophages and regulates VFH pathogenesis;however,the underlying mechanism remains unclear.AIM To explore how FGL2 regulates macrophage function and subsequent liver injury during VFH.METHODS Murine hepatitis virus strain 3(MHV-3)was used to induce VFH in FGL2-deficient(Fgl2-/-)and wild-type(WT)mice.The dynamic constitution of hepatic macrophages was examined.Adoptive transfer of Fgl2-/-or WT bone marrowderived macrophages(BMDMs)into WT recipients with macrophages depleted prior to infection was carried out and the consequent degree of liver damage was compared.The signaling cascades that may be regulated by FGL2 were detected in macrophages.RESULTS Following MHV-3 infection,hepatic macrophages were largely replenished by proinflammatory monocyte-derived macrophages(MoMFs),which expressed high levels of FGL2.In Fgl2-/-mice,the number of infiltrating inflammatory MoMFs was reduced compared with that in WT mice after viral infection.Macrophage depletion ameliorated liver damage in WT mice and further alleviated liver damage in Fgl2-/-mice.Adoptive transfer of Fgl2-/-BMDMs into macrophage-removed recipients significantly reduced the degree of liver damage.Inhibition of monocyte infiltration also significantly ameliorated liver damage.Functionally,Fgl2 deletion impaired macrophage phagocytosis and the antigen presentation potential and attenuated the proinflammatory phenotype.At the molecular level,FGL2 deficiency impaired IRF3,IRF7,and p38 phosphorylation,along with NF-κB activation in BMDMs in response to viral infection.CONCLUSION Infiltrated MoMFs represent a major source of hepatic inflammation during VFH progression,and FGL2 expression on MoMFs maintains the proinflammatory phenotype via p38-dependent positive feedback,contributing to VFH pathogenesis.
基金Supported by National Natural Science Foundation of China, No. 30270607
文摘AIM： To delineate the mechanisms of renal vasoconstriction in hepatorenal syndrome （HRS）, we investigated the expression of type I inositol 1, 4, 5-triphosphate receptors （IP3R I） of kidney in mice with fulminant hepatic failure （FHF）. METHODS： FHF was induced by lipopolysaccharide （LPS） in D-galactosamine （GAIN） sensitized BALB/c mice. There were 20 mice in normal saline （NS）-treated group, 20 mice in LPS-treated group, 20 mice in GaIN- treated group, and 60 mice in GalN/LPS-treated group （FHF group）. Liver and kidney tissues were obtained at 2, 6, and 9 h after administration. The liver and kidney specimens were stained with hematoxylin-eosin for studying morphological changes under light microscope. The expression of IP3R I in kidney tissue was tested by immunohistochemistry, Western blot and reverse transcription （RT）-PCR. RESULTS： Kidney tissues were morphologically normal at all time points in all groups. IP3R I proteins were found localized in the plasma region of glomerular mesangial cells （GMC） and vascular smooth muscle cells （VSMC） in kidney by immunohistochemical staining. In kidney of mice with FHF at 6 h and 9 h IP3R I staining was upregulated. Results from Western blot demonstrated consistent and significant increment of IP3R I expression in mice with FHF at 6 h and 9 h （t = 3.16, P 〈 0.05; t = 5.43, P 〈 0.01）. Furthermore, we evaluated IP3R I mRNA expression by RT-PCR and observed marked upregulation of IP3R I mRNA in FHF samples at 2 h, 6 h and 9 h compared to controls （t = 2.97, P 〈 0.05; t = 4.42, P 〈 0.01; t = 3.81, P 〈 0.01）. CONCLUSION： The expression of IP3R I protein increased in GMC and renal VSMC of mice with FHF, possibly caused by up-regulation of IP3R I mRNA.
文摘AIM: To examine if fulminant Clostridium difficile infections(CDI) resulting in colectomy was associated with a prior appendectomy and whether any association affected the severity of the disease.METHODS: A retrospective chart review was performed on patients who underwent colectomy for CDI between 2001 and 2011.The appendectomy rate was calculated based on the absence of an appendix on the surgical pathology report.This was compared to an established lifetime risk of appendectomy in the general population.A chart review was performed for mortality and traditional markers of CDI disease severity.Fisher’s exact test was used to calculate the likelihood of association between prior appendectomy,mortality,and clinical markers of severity of infection.RESULTS: Fifty-five specimens were identified with pseudomembranous colitis consistent with CDI.All patients had a clinical history consistent with CDI and 45 of 55(81.8%) specimens also had microbiological confirmation of CDI.Appendectomy was observed in 24 of 55 specimens(0.436,99%CI: 0.280-0.606).This was compared to the lifetime incidence of appendectomy of 17.6%.The rate of appendectomy in our sample was significantly higher than would be expected in the general population(43.6% vs 17.6%,P 【 0.01).Disease severity did not differ based on presence or absence of an appendix and no association was detected between prior appendectomy and mortality(OR = 0.588,95%CI: 0.174-1.970).CONCLUSION: The rate of appendectomy in the patients whose CDI led to colectomy,was significantly higher than the calculated lifetime risk,suggesting an association of appendectomy and severe CDI resulting in colectomy.Larger prospective studies are needed to assess any potential causal relationships affecting fulminant CDI.
基金Supported by National Basic Research Program of China,No.2009CB522401grand from Natural Science Foundation ofChina,No. 30870983 and 30971118
文摘AIM:To establish an appropriate primate model of fulminant hepatic failure (FHF).METHODS:We have,for the first time,established a large animal model of FHF in Macaca mulatta by intraperitoneal infusion of amatoxin and endotoxin.Clinical features,biochemical indexes,histopathology and iconography were examined to dynamically investigate the progress and outcome of the animal model.RESULTS:Our results showed that the enzymes and serum bilirubin were markedly increased and the enzyme-bilirubin segregation emerged 36 h after toxin administration.Coagulation activity was significantly decreased.Gradually deteriorated parenchymal abnormality was detected by magnetic resonance imaging (MRI) and ultrasonography at 48 h.The liver biopsy showed marked hepatocyte steatosis and massive parenchymal necrosis at 36 h and 49 h,respectively.The autopsy showed typical yellow atrophy of the liver.Hepatic encephalopathy of the models was also confirmed by hepatic coma,MRI and pathological changes of cerebral edema.The lethal effects of the extrahepatic organ dysfunction were ruled out by their biochemical indices,imaging and histopathology.CONCLUSION:We have established an appropriate large primate model of FHF,which is closely similar to clinic cases,and can be used for investigation of the mechanism of FHF and for evaluation of potential medical therapies.
文摘BACKGROUND: Fulminant hepatic failure (FHF) is not uncommon in our clinical practice in Bangladesh. There was a rise in acute hepatitis E virus (HEV) in Bangladesh after the 2004 floods. At that time, most of the country was under water for more than a month, leading to sewage contamination of the water supply. The aim of this study was to investigate the etiology of FHF in Bangladesh. METHODS: In this retrospective study, 23 patients with FHF who presented with severe impairment of hepato- cellular function (i.e. encephalopathy, coagulopathy and jaundice) within 6 months of onset of symptoms were included. There were 17 men and 6 women, aged from 18 to 32 years. Four of the women were pregnant. Patients were tested for markers for common hepatotrophic viruses. A relevant history was taken and the Patient Record Book of the Unit was reviewed. RESULTS: 56.52% patients (13/23) had HEV infection, and all were anti-HEV IgM-positive tested by ELISA. HBV infection was detected in 34.78% patients (8/23), all of whom were tested positive for either HBsAg or anti-HBs IgM by ELISA. 8.7% patients (2/23) had a positive history for intake of alcohol and/or drugs. CONCLUSIONS: Acute HEV infection is the leading cause of FHF in Bangladesh. Sewage contamination of the water supply following floods contributes to a higher incidence of HEV infection. HBV infection is also important.
