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Sepsis is a life-threatening organ dysfunction caused by the disorder of the body's response to infection, and is one of the main causes of death in critically ill patients. Ferroptosis is a kind of iron dependent cell death, characterized by intracellular reactive oxygen species (ROS) accumulation. Sepsis can cause a substantial accumulation of ROS in cells. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator of antioxidant and plays a critical protective role in sepsis induced ferroptosis by regulating the expression of proteins related to the ferroptosis pathway. Current studies have found that activation of Nrf2 has a protective effect on ferroptosis induced by sepsis. In this paper, we summarized the regulation mechanism of Nrf2 in ferroptosis, in order to provide references for the treatment of sepsis.
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Objective:To investigate the etiology, prognosis and clinical characteristics of abnormal serum amylase and lipase in children.Methods:This study was a retrospective study.A total of 7 813 children older than 28 days who had their serum amylase and lipase detected in Hunan Children′s Hospital from August 2017 to August 2020 were included as the study subjects.Children with acute and chronic pancreatitis were excluded.The age, gender, impatient department, imaging exams, discharge outcomes, main diagnosis, diagnostic ICD10 code, and the highest values of serum amylase and lipase during hospitalization were collected through the medical record system.According to the levels of serum amylase and lipase, the children were divided into 3 groups.Patients in group A had normal serum amylase and serum lipase levels.The serum amylase or lipase levels of patients in group B was 1 to 3 times higher than that of group A. The serum amylase or lipase levels in group C was 3 times higher than that of group A. Group B and group C had abnormal pancreatic enzyme levels.According to the prognosis, patients were divided into the survival group and the death group.The relationship of the occurrence of abnormal serum amylase and lipase levels with the age, sex, disease type and prognosis of children was analyzed.Results:The ratio of abnormal trypsin in male and female was 11.5% and 12.9%, respectively.The number of children with abnormal pancreatic enzyme levels in the 28 day -1 year old group, >1-3 years old group, >3-6 years old group, >6 -12 years old group and > 12 year old group were 37 cases (4.6%), 185 cases (15.4%), 199 cases (10.5%), 431 cases (13.9%), and 94 cases (11.7%), respectively.The mortality rate was 1.6% (112/6 867 cases) in group A, 5.2% (32/617 cases) in group B, and 7.6% (25/329 cases) in group C. The mortality risk of group B and C was both higher than that of group A. Compared with group A, the OR (95% CI) of group B and group C was 3.30 (2.21-4.93) and 4.96 (3.17-7.77), respectively.In group C, the top five diseases were parotitis (26.4%), cholangiectasis (11.6%), choledochal cysts (8.5%), gastroenteritis (4.5%) and sepsis (3.3%). Conclusions:Pancreatic enzyme abnormalities in children are associated with adverse prognosis.Pancreatic enzyme abnormalities are more prone to occur in children aged >1-3 with mumps, digestive diseases and congenital digestive system structural deformities.In addition, children with sepsis are also easy to present pancreatic enzyme abnormalities.Clinical attention should be paid to the possibility of secondary pancreatic damage in children with sepsis.
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Objective:To investigate the value of the level of heparin-binding protein(HBP)in bronchoalveolar lavage fluid(BALF)on the evaluation of severe pneumonia in children.Methods:A total of 94 children with severe pneumonia who underwent bronchoscopy and bronchoalveolar lavage were admitted at Hunan Children′s Hospital, and HBP levels in BALF were detected.According to the etiological results, the patients were divided into non-bacterial infection group(19 cases) and bacterial infection group(75 cases). According to the existence and severity of acute respiratory distress syndrome (ARDS), the cases were divided into non-ARDS group(65 cases), mild ARDS group(23 cases) and moderate to severe ARDS group(6 cases).Results:The HBP level of BALF in the bacterial infection group was higher than that in the non-bacterial infection group, and the difference was statistically significant[ 20.77(5.90, 73.50)ng/mL vs.5.9(5.90, 7.64)ng/mL, Z=12.500, P<0.001]. The HBP level of BALF in the moderate to severe ARDS group[300.00(169.29, 300.00)ng/mL] was significantly higher than those in the non-ARDS group[11.90(5.90, 36.95)ng/mL] and the mild ARDS group[15.13(7.41, 46.44)ng/mL], and the difference was statistically significant( H=14.718, P=0.001). In predicting the presence of bacterial infection in severe pneumonia, the area under the receiver operating characteristic curves of BALF HBP, serum procalcitonin (PCT) and serum C-reactive protein(CRP) were 0.758, 0.737, and 0.732, respectively.When the optimal truncation values of BALF HBP, serum PCT and serum CRP were 8.40 ng/mL, 0.16 ng/mL, and 8.39 mg/L, the predicted sensitivities were 70.7%, 69.3%, 46.7%, and the predicted specificity were 79.0%, 79.0%, 94.7%, respectively. Conclusion:The level of HBP in BALF in children with severe pneumonia increases with the severity of ARDS, and significantly increases in the positive group of bacterial infection, which can be used as one of the auxiliary indicators to evaluate the severity of severe pneumonia and bacterial infection in children.
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Objective:To discuss the role of continuous blood purification (CBP) therapy in children with severe adenovirus pneumonia.Methods:A total of 114 children with severe adenovirus pneumonia admitted to the Department of PICU at Children′s Hospital of Hunan Province from June 2018 to July 2019 were selected as the research objects.According to whether treated with CBP, they were divided into CBP group and control group.The following indicators during the process of treatment were compared between two groups, including respiratory mechanics indicators[respiratory index(PaO 2/FiO 2), dynamic lung compliance(Cdyn)]; hemodynamic indicators(heart rate and mean arterial pressure); changes in levels of inflammatory factors interleukin(IL)-6, IL-10, tumor necrosis factor(TNF)-α and the prognosis 28 days after admission. Results:The respiratory mechanics index, serum IL-6 and TNF-α levels of two groups after treatment were significantly lower than those before treatment, and the serum IL-10 level was significantly higher than that of this group before treatment.There were statistical differences in the CBP group before and after treatment, while there was no statistical difference in control group.In the CBP group, the serum IL-6 and TNF-α levels after treatment were significantly lower than those of the control group( P<0.05), and the serum IL-10 level was significantly higher than that of the control group( P<0.05). The 28-day mortality rate of patients in CBP group was 8.6%(3/35), which was significantly lower than 13.9%(11/79) of control group ( P<0.05). Conclusion:CBP could improve the main respiratory mechanical indexes of adenovirus pneumonia and decrease the level of inflammatory cytokines.
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Objective:To analyze the epidemiological characteristics, clinical characteristics and blood purification effect of mushroom poisoning in children.Methods:A retrospective study was conducted on 51 children with acute mushroom poisoning admitted to Hunan Children′s Hospital from 2002 to 2020.The epidemiological and clinical characteristics were analyzed, and the prognosis of children with different incubation periods was analyzed and compared.Among them, 36 critically ill children were treated with blood purification.Results:The age distribution was 66(43, 115)months.Mushroom poisoning had obvious seasonal and spatial aggregation.The first symptom was mainly manifested by digestive tract, which was manifested as vomiting, abdominal pain and diarrhea, accounting for 94.1% patients(48/51). The gastrointestinal tract type accounted for 45.1%(23/51) of the clinical types and the multi-organ damage type accounted for 51.0% patients(26/51). The length of hospital stay was 6(3, 11)days.Among them, early onset accounted for 45.1% patients(23/51), late onset accounted for 54.9% patients(28/51). Early onset hospitalization was shorter, about 4(2, 7)days, and fewer organs 1(0, 3) were damaged.The length of hospital stay of late onset was 8(3, 12)days, and the number of damaged organs was 4(2, 4). There was a statistically significant difference( P<0.05). Late onset patients had more severe organ function damage, including liver function, coagulation function, renal function, myocardial enzyme, and there was no significant difference in the final outcome between two groups.In 36 children who were given blood purification treatment, alanine aminotransferase, aspartate aminotransferase, prothrombin time, international normalized ratio, blood urea nitrogen, and lactate dehydrogenase were significantly improved, with statistically significant differences( P<0.05). Conclusion:Mushroom poisoning has obvious seasonal and geographical distribution characteristics; the first manifestation is mainly gastrointestinal symptoms; the clinical types are more common in gastrointestinal and multiple organ damage types.Children with early onset have shorter hospital stays and fewer complications than later onset.Blood purification treatment can significantly improve liver function, kidney function and blood coagulation function in children with toadstool poisoning.
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Objective:To summary the mixed infection as well as clinical characteristics and analyze the risk factors for mixed infection of severe adenovirus pneumonia(SAP) in children.Methods:The clinical data of 114 children with SAP were retrospectively analyzed.Multivariate Logistic regression analysis was performed to assess the risk factors for mixed infection.Results:The incidence age was from 6 months to 2 years(62.5%). High fever(94.7%), cough(98.2%), dyspnea(86.8%) and lethargy(95.6%) were the main symptoms.Laboratory examination showed that children with SAP were prone to increased white blood cell count, C-reactive protein, procalcitonin, aspartate aminotransferase, alanine aminotransferase and CK-MB, as well as decreased proportion of CD3 + , CD4 + , CD8 + , CD4 + /CD8 + and NK cells.The main complications intrapulmonary organ were respiratory failure(80.7%). The main complications extrapulmonary organ were circulatory complications (55.3%). SAP was easily combined with other pathogenic infections.Streptococcus pneumoniae(22.9%)was the most common bacterial pathogen.Respiratory syncytial virus(10.0%)were the most common virus, in addition, mycoplasma pneumoniae(17.1%) was also common.Multivariable Logistic regression analysis showed that the decreasing ratio of CD4 + /CD8 + and NK cells, congenital heart disease and congenital airway dysplasia were the independent risk factors for mixed infection of SAP in children( P<0.05). Conclusion:The SAP patients could easily suffer from mixed infection and high fatality rate.Immune dysregulation is the important risk factors for mixed infection of SAP in children.So immunoregulatory treatment is very important.
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Objective:To investigate the changes of inflammatory factors, serum amylase and lipase and pancreatic damage at different time points after establishment of cecal ligation and perforation in a rat model of sepsis, which provides a stable and reliable animal model for the study of pancreatic injury following sepsis in children.Methods:Sixty male SD rats were randomly divided into 6 h group, 12 h group, 24 h group and 48 h group in control group, sham group and cecal ligation and puncture (CLP) group.Rat model of sepsis was established by cecal ligation and perforation in CLP group, the sham group was treated with sham operation, and rats in control group were not treated.The levels of interleukin (IL)-1β, IL-10, amylase and lipase in each group were detected, and pancreatic tissue was taken for HE staining.Results:In this model, the 48 h survival rate of rats in the CLP group was 70%.With the prolongation of postoperative time in the CLP group, pancreatic tissue congestion, cell edema, and inflammatory cell infiltration gradually worsened.The pathological changes of pancreatic tissue in the Sham group were mild.The expression levels of IL-1β in CLP group and sham group increased first and then decreased, and reached the peak at 12 h. The expression levels of IL-1β in CLP group were significantly higher than those in control group and sham group at all time points( P<0.05). The expression level of IL-10 showed a gradually increasing trend, reaching a peak at 48 h. The expression level of IL-10 in CLP group was significantly higher than that in control group and sham group at all time points( P<0.05), which in sham group was significantly higher than that in control group( P<0.05). Serum amylase and lipase in CLP group showed an upward and then downward trend, reaching the peak at 24 h. The serum amylase levels at 24 h and 48 h were significantly higher than those in control group and sham group( P<0.05). Serum amylase levels in sham group were significantly different from those in control group at 12 h, 24 h and 48 h( P<0.05). Serum lipase level at 12 h, 24 h and 48 h was significantly higher than that in control group and sham group( P<0.05). There was no significant difference in serum lipase between sham group and control group( P>0.05). Conclusion:After CLP modeling, IL-1β, IL-10 elevation and pancreatic pathological changes appeared at the early stage, and the pathological changes gradually increased with time.Significant differences in serum amylase and lipase began to appear at 24 h and 12 h respectively.
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Objective:To evaluate the effect of serum cytokines and immune typing on the severity and prognosis of children with sepsis.Methods:One hundred and sixty children with sepsis admitted to No.2 PICU from May 2018 to May 2019 at Hunan Children′s Hospital were enrolled.Vital signs, blood routine and blood biochemical indexes of the children were collected within 24 hours after admission.Serum cytokine concentrations of interleukin(IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor(TNF)-α, and interferon (IFN)-γ were tested at the same time.According to the worst condition during the first 24 h after admission, and the consensus diagnostic criteria of experts in the diagnosis and treatment of septic shock in children in 2015, the patients were divided into sepsis group(76 cases) and severe sepsis group(84 cases). According to the prognosis of 28 days, the patients were divided into survival group(134 cases)and death group(26 cases). The differences of cytokine concentration and the composition of immune state among groups were compared.Results:The levels of IL-2[2.40(2.40, 2.55)pg/mL vs. 2.40(2.40, 3.76)pg/mL], IL-6[60.54(23.22, 250.38)pg/mL vs. 21.47(8.83, 57.94)pg/mL], IL-10[50.85(21.74, 217.12)pg/mL vs. 14.99(9.23, 28.79)pg/mL] , TNF-α[2.75(2.40, 5.15)pg/mL vs. 2.40(2.40, 3.23)pg/mL] and IFN-γ[8.01(4.34, 37.28)pg/mL vs.2.62(2.62, 28.56)pg/mL] in the severe sepsis group were significantly higher than those in the sepsis group( P<0.05). The levels of IL-10[99.57(10.51, 646.96)pg/mL vs. 23.17(11.74, 57.30)pg/mL] and TNF-α[3.08(2.40, 5.13)pg/mL vs. 2.45(2.40, 3.80)pg/mL] in the death group were significantly higher than those in the survival group( P<0.05). The risk of death in children with mixed antagonistic response syndrome (MARS) was significantly higher than those without MARS( OR 3.75, 95% CI 1.302-10.804). Conclusion:The increased concentrations of IL-2, IL-6, IL-10, TNF-α, and IFN-γ are significantly correlated with the severity of sepsis in children.Increased IL-10 concentration and the occurrence of MARS are significantly correlated with poor prognosis.The occurrence of MARS in children with sepsis should be highly vigilant for the poor prognosis.
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Objective:To analyze the predictive value of the mortality risk score for severe hand, foot and mouth disease(MRSHFMD) system for the complications and mortality risk of severe hand, foot and mouth disease(HFMD) in children.Methods:This study included 354 children with severe HFMD who admitted in the pediatric intensive care unit(PICU) of Hunan Provincial Children′s Hospital from March 2012 to March 2014.The patients were grouped according to whether they had complicated nervous system damage, pulmonary edema, pulmonary hemorrhage and circulatory failure in the course of disease, and the prognosis was grouped according to their 28 d survival.The worst values of white blood cell count, blood glucose, blood lactic acid, N-terminal pro-brain natriuretic peptide, within 24 hours after admission were used to score MRSHFMD.The predictive value of MRSHFMD for nervous system damage, pulmonary edema, pulmonary hemorrhage, circulatory failure, and prognosis were evaluated using the receiver operating characteristic(ROC)curve.Results:The blood glucose, white blood cell count, blood lactic acid value, N-terminal pro-brain natriuretic peptide and MRSHFMD score of the children with HFMD complicated with nervous system damage, pulmonary edema, pulmonary hemorrhage and circulatory failure were significantly higher than those in the non-complicated groups( P<0.01). When the cut-off value of MRSHFMD score was 3, the area (95% CI) under the ROC curve were 0.723 (0.643-0.804), 0.870 (0.793-0.946), 0.921 (0.85-0.992), 0.944 (0.867-1.000) and 0.954 (0.000-1.000) of nervous system damage, pulmonary edema, pulmonary hemorrhage, circulation failure and death in children with HFMD, respectively.The specificity and sensitivity of predicting nervous system damage, pulmonary edema, pulmonary hemorrhage, circulatory failure and death were 44.6% and 95.8%; 67.5% and 95.5%; 83.3% and 95.1%; 89.3% and 95.1%; 90.9% and 93.7%, respectively. Conclusion:MRSHFMD system is an effective tool to predict HFMD complications of pulmonary hemorrhage, circulatory failure, and death, which is worthy of clinical promotion.
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Objective@#To analyze the predictive value of the mortality risk score for severe hand, foot and mouth disease(MRSHFMD) system for the complications and mortality risk of severe hand, foot and mouth disease(HFMD) in children.@*Methods@#This study included 354 children with severe HFMD who admitted in the pediatric intensive care unit(PICU) of Hunan Provincial Children′s Hospital from March 2012 to March 2014.The patients were grouped according to whether they had complicated nervous system damage, pulmonary edema, pulmonary hemorrhage and circulatory failure in the course of disease, and the prognosis was grouped according to their 28 d survival.The worst values of white blood cell count, blood glucose, blood lactic acid, N-terminal pro-brain natriuretic peptide, within 24 hours after admission were used to score MRSHFMD.The predictive value of MRSHFMD for nervous system damage, pulmonary edema, pulmonary hemorrhage, circulatory failure, and prognosis were evaluated using the receiver operating characteristic(ROC)curve.@*Results@#The blood glucose, white blood cell count, blood lactic acid value, N-terminal pro-brain natriuretic peptide and MRSHFMD score of the children with HFMD complicated with nervous system damage, pulmonary edema, pulmonary hemorrhage and circulatory failure were significantly higher than those in the non-complicated groups(P<0.01). When the cut-off value of MRSHFMD score was 3, the area (95%CI) under the ROC curve were 0.723 (0.643-0.804), 0.870 (0.793-0.946), 0.921 (0.85-0.992), 0.944 (0.867-1.000) and 0.954 (0.000-1.000) of nervous system damage, pulmonary edema, pulmonary hemorrhage, circulation failure and death in children with HFMD, respectively.The specificity and sensitivity of predicting nervous system damage, pulmonary edema, pulmonary hemorrhage, circulatory failure and death were 44.6% and 95.8%; 67.5% and 95.5%; 83.3% and 95.1%; 89.3% and 95.1%; 90.9% and 93.7%, respectively.@*Conclusion@#MRSHFMD system is an effective tool to predict HFMD complications of pulmonary hemorrhage, circulatory failure, and death, which is worthy of clinical promotion.
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Objective To observe the effect of curcumin on myocardial mitochondrial related gene (mtATP6), high mobility group box 1(HMGB1) mRNA expression and plasma HMGB1 level in rats with sepsis, and to explore a new strategy for protection of myocardial injury in sepsis.Methods A rat sepsis model was established by cecal ligation and puncture (CLP). Thirty male Sprague-Dawley rats were randomly (random number) divided into the sham operation group (sham group), sepsis group (CLP group), and curcumin intervention group (Cur group), with 10 rats in each group. Rats in the Cur group were treated with curcumin by intraperitoneal injection at 100 mg/kg, and normal saline was injected into rats in the sham and CLP groups. Five rats were randomly (random number) sacrificed at 6 h and 24 h after modeling. The pathological changes of myocardial tissue were observed under light microscope. The levels of CK and CK-MB in serum were detected. The HMGB1 level in plasma was detected by ELISA. Real-time PCR was used to detect the expression of HMGB1 mRNA and mtATP6 in myocardial tissue. One-way ANOVA were performed in multigroup mean comparison, LSD-t test was used to compare the mean values of two samples, andP<0.05 was considered statistically significant.Results The pathological score of myocardial tissue in the Cur group was lower than those in the CLP group at 6 h and 24 h (P<0.05). The CK and CK-MB in the Cur group were lower than those in the CLP group at 6 h and 24 h (P<0.05). The levels of HMGB1 in the Cur group were lower than those in the CLP group at 6 h and 24 h (P<0.05). The expression levels of HMGB1 mRNA and mtATP6 in myocardial tissue of the CLP group were lower than those in the sham group at 6 h (P<0.05), while the expression levels of HMGB1 mRNA and mtATP6 in myocardial tissue of the Cur group were higher than those in the CLP group at 6 h, but the difference was not statistically significant (P>0.05).Conclusion Curcumin protects acute myocardial injury by affecting HMGB1 release and translocation down-regulation of extracellular levels and regulation of mtATP6 expression in CLP model rats.
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Objective@#To observe the effect of curcumin on myocardial mitochondrial related gene (mtATP6), high mobility group box 1(HMGB1) mRNA expression and plasma HMGB1 level in rats with sepsis, and to explore a new strategy for protection of myocardial injury in sepsis.@*Methods@#A rat sepsis model was established by cecal ligation and puncture (CLP). Thirty male Sprague-Dawley rats were randomly (random number) divided into the sham operation group (sham group), sepsis group (CLP group), and curcumin intervention group (Cur group), with 10 rats in each group. Rats in the Cur group were treated with curcumin by intraperitoneal injection at 100 mg/kg, and normal saline was injected into rats in the sham and CLP groups. Five rats were randomly (random number) sacrificed at 6 h and 24 h after modeling. The pathological changes of myocardial tissue were observed under light microscope. The levels of CK and CK-MB in serum were detected. The HMGB1 level in plasma was detected by ELISA. Real-time PCR was used to detect the expression of HMGB1 mRNA and mtATP6 in myocardial tissue. One-way ANOVA were performed in multigroup mean comparison, LSD-t test was used to compare the mean values of two samples, and P<0.05 was considered statistically significant.@*Results@#The pathological score of myocardial tissue in the Cur group was lower than those in the CLP group at 6 h and 24 h (P<0.05). The CK and CK-MB in the Cur group were lower than those in the CLP group at 6 h and 24 h (P<0.05). The levels of HMGB1 in the Cur group were lower than those in the CLP group at 6 h and 24 h (P<0.05). The expression levels of HMGB1 mRNA and mtATP6 in myocardial tissue of the CLP group were lower than those in the sham group at 6 h (P<0.05), while the expression levels of HMGB1 mRNA and mtATP6 in myocardial tissue of the Cur group were higher than those in the CLP group at 6 h, but the difference was not statistically significant (P>0.05).@*Conclusion@#Curcumin protects acute myocardial injury by affecting HMGB1 release and translocation down-regulation of extracellular levels and regulation of mtATP6 expression in CLP model rats.
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Sepsis is a major cause of secondra y pancreatic injury in critically ill children.A lagr e number of inflammatoyr m ediators werer elesa ed after acute ijn ury of the pancreas,which may aggravate the inflammatory reaction and the stress reaction.Nuclear factor E2-related factor 2(Nrf2),an important protec-tive transcription factor,could activate the expression of more than 500 genes.Most of the genes have the function of cytoprotection.Studise have dem onts rated that Nrf2 plays a certain role in cytoprotection,such as regulating the inflammatory response,anti-oxidative stress,improving mitochondrial functoi n and decreasing toxic protein aggregation.This review explored the protective mechanism of Nrf2 in pancreatic injury caused by sepis s.