The incidence of cardiovascular dysfunction in the early stage of sepsis is high,early detection and timely treatments are beneficial to reduce the mortality of sepsis.Biological markers are known to play a very important role in detecting and treating sepsis.The aim of this article was to review the relationship between Pentraxin 3 and sepsis with cardiovascular dysfunction.

OBJECTIVETo study the value of Pentraxin 3 (PTX3) in diagnosing the severity and cardiovascular function of the critically ill children. Method A total of 178 patients who were older than 28 days, with acute infection of respiratory or neurological system, excluding chronic or special disease, and admitted to the pediatric intensive care unit (PICU) of Hunan Children's Hospital from October 1, 2013 to April 30, 2014 were enrolled, including 102 male cases and 76 female cases. The ages ranged from 1 month to 13 years and 1 month, 78 of them were less than 1 year old ; 58 cases were between 1 to 3 years old; 42 cases were above 3 years old; 101 cases were diagnosed as respiratory system diseases, 77 cases had nervous system diseases. PTX3 was detected with enzyme-linked immunosorbent assay (ELISA) within 1 d after enrollment, at 3 days and 7 days, meanwhile, troponin, myocardial enzyme, brain-type natriuretic peptide (BNP), C-reactive protein (CRP), plasma calcitonin (PCT) and WBC etc. Were measured. According to the plasma PTX3 value which were measured within 24 h after enrollment the patients were divided into three groups: mildly elevated group (< 44 µg/L) 41 cases; moderately elevated group (44 - < 132 µg/L) in 66 cases; severely elevated group 71 cases (132 µg/L or higher). Those 178 patients were divided into 3 groups according to the degree of infection: non-sepsis group (78 cases), sepsis group (70 cases), severe sepsis group (30 cases), and in each group, those with heart failure were respectively 19 cases, 28 cases, 17 cases. Analysis of the plasma PTX3 expression changes in different clinical manifestations, different condition, different degrees of organ damages and prognosis for the patient. The continuous variables were analyzed with t-test, F-test, H-test, the categorical variables were analyzed with Chi-square test, and the correlation analysis was performed to calculate Pearson coefficients.

RESULTThe PTX3 value measured within 24 h after enrollment increased with the degree of infection (50. 4(35. 2,70. 4) µg/L; 175. 8 (99. 6, 309. 9) µg/L;419. 9 (168. 3, 468. 6) µg/L; H = 88. 345, P = 0. 000). PTX3 level gradually declined, while in severe sepsis group decreased slowly (P <0. 05); the area under the ROC curve of Plasma PTX3 was larger than that of other inflammatory markers such as CRP and PCT, white blood cells and neutrophils in the diagnosis of sepsis; while the former three are PTX3, PCT and CRP (the sensitivity and specificity respectively were 0. 77, 0. 68; 0. 66, 0. 6; 0. 47, 0. 55); the PTX3 value of the severely elevated group was significantly higher than those of the mildly and moderately elevated groups (P <0. 05). The proportion of having 3 or more organs failure increased as the PTX3 rising among the groups of mildly elevated group, moderately elevated group and severely elevated group (1(2. 4%), 4(6. 1%), 14(19. 7%) χ2 =16. 16,P = 0. 000); and in each group, the proportion of having good and poor prognosis for these three groups were different (33 (80.5%) and 8 (19. 5%), 35 (53%) and 31 (47%), 28 (39.4%) and 43 (60.6%), χ = 17. 663, P = 0. 000). The K-M curve for these three groups had statistically significant difference (χ2 = 7. 086, P = 0. 029). Those with heart failure had higher PTX3 value than those in non-heart failure at the same degree of infection. PTX3 value increased with myocardial enzyme (troponin, creatine kinase isoenzyme, BNP) levels. In the diagnosis of heart failure, the area under the ROC curve were respectively PTX3 0. 824; BNP 0. 772; CM-KB 0. 643; CNTIO. 671, the sensitivity and specificity were PTX3 0. 8, 0. 58; CK-MB 0. 56,0. 79; CTNI 0. 60,0. 69; BNP 0. 73, 0. 58. In terms of predicting the prognosis of sepsis with heart failure complications, the PTX3 value's area under ROC curve was larger than that of BNP (respectively 0. 844, 0. 472).

CONCLUSIONThe PTX3 is an objective biochemical marker in diagnosis of sepsis; it is helpful in assessment of severity and prognosis of sepsis; it also has a certain clinical value in the assessment of sepsis cardiovascular function damage.

Adolescent ; Biomarkers ; blood ; C-Reactive Protein ; analysis ; Calcitonin ; blood ; Cardiovascular System ; physiopathology ; Child ; Child, Preschool ; Creatine Kinase ; blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Infant ; Intensive Care Units, Pediatric ; Leukocyte Count ; Male ; Natriuretic Peptide, Brain ; blood ; Prognosis ; Protein Precursors ; blood ; ROC Curve ; Sensitivity and Specificity ; Sepsis ; diagnosis ; physiopathology ; Serum Amyloid P-Component ; analysis ; Troponin ; blood

Objective To determine the levels of blood pancreatic stone protein/ regenerating protein(PSP/reg)and to explore the value of PSP/ reg in assessing severity and predicting prognosis of sepsis with or without panc-reatic damage. Methods In this prospective study,the clinical data and blood samples to measure PSP/ reg levels in 1,3 and 7 days after admission in the Pediatric Intensive Care Unit,Hunan Children's Hospital,from the children with sepsis from September 2013 to September 2014 were collected. According to levels of pancreatic trypsin(amylase or li-pase),the children were divided into normal group,mildly elevated group(1 - 3 times),and severely elevated group (more than 3 times);based on the condition of sepsis,the children were divided into sepsis group and severe sepsis group. Chi - square test,nonparametric rank sum test,Spearman correlation and area under the receiver operating cha-racteristic curve(AUC),Kaplan - Meier survival curves were used for statistical analysis. Results (1)A total of 226 children with sepsis were included in this study,among them pancreatic trypsin was normal in 159 cases(70. 4% ), pancreatic trypsin mildly elevated in 44 cases( 19. 4% ),and pancreatic trypsin severely elevated in 23 cases (10. 2% );125 cases(55. 3% )were sepsis,and 101 cases(44. 7% ,of which 29 cases were sepsis shock)were severe sepsis.(2)The correlation between PSP/ reg and serum amylase was maximum,while PSP/ reg had some correlation with serum lipase,but there was no correlation with C - peptide,insulin,glucose.(3)When pancreatic trypsin was normal or mildly elevated,severe sepsis group had higher levels of PSP/ reg than that of sepsis group(Z = - 7. 627,- 2. 965,P =0. 000,0. 003);while pancreatic trypsin was severe elevated,there was no significant difference in PSP/ reg levels be-tween sepsis group and severe sepsis group(Z = - 0. 134,P = 0. 894).(4)The AUC of PSP/ reg and procalcitonin to assess severity of sepsis were greater than 0. 7 in the children whose pancreatic trypsin was normal or mildly elevated, and there was no significant difference between them(P ﹥ 0. 05);while the AUC of C - reactive protein and WBC were less than 0. 7.(5)PSP/ reg levels gradually increased in non - survival children in 3 and 7 days,while survival children gradually declined. The AUC of PSP/ reg to predict prognosis was 0. 775,and 60 μg/ L was viewed as the critical point, sensitivity 89% ,specificity 67% . Children with PSP/ reg levels ≤60 μg/ L had higher rate of survival than children with ﹥ 60 μg/ L(χ2 = 36. 874,P = 0. 000). Conclusions PSP/ reg is closely associated with pancreatic exocrine func-tion,but PSP/ reg still can assess severity and predict prognosis in children with sepsis and pancreatic damage.

[ ABSTRACT] AIM: To investigate the protective effect of autophagy on oxidized low density lipoprotein ( ox-LDL)-induced macrophage apoptosis and the underlying molecular mechanisms .METHODS:The RAW264.7 macropha-ges were pretreated with 3 mmol/L 3-methyladenine (3-MA), 1 μmol/L rapamycin (Rap) or 4 mmol/L 4-phenylbutyric acid ( PBA) respectively for 1 h and then treated with ox-LDL (100 mg/L) for 12 h.The cell viability and apoptosis were determined by MTT assay and flow cytometry with Annexin V-FITC/PI staining, respectively.The activities of lactate de-hydrogenase ( LDH) in the medium and caspase-3 in the cells were determined by detection kits .The protein levels of bec-lin-1 (a molecular marker of autophagy ), glucose-regulated protein 78 (GRP78, an endoplasmic reticulum stress marker) and C/EBP homologous protein ( CHOP, a key-signaling component of endoplasmic reticulum stress-induced apoptosis ) were examined by Western blot .Microtubule-associated protein 1 light chain 3 (LC3, another molecular marker of autoph-agy) was observed under laser scanning confocal microscope .RESULTS: Treatment of the RAW264.7 macrophages with ox-LDL at 100 mg/L for 12 h resulted in significant decrease in cell viability , and dramatic elevation in LDH leakage , cell apoptosis and caspase-3 activity, which were promoted by 3-MA (an autophagy inhibitor) and inhibited by Rap (an autoph-agy inducer ) .ox-LDL induced autophagy in the macrophages as assessed by beclin-1 upregulation and frequent granulation of LC3, which were inhibited by 3-MA and promoted by Rap.Interestingly, 3-MA enhanced, while Rap blocked, the CHOP upregulation induced by ox-LDL.Moreover , PBA ( endoplasmic reticulum stress inhibitor ) significantly inhibited ox-LDL-induced GRP78 upregulation and autophagy as determined by the attenuation of beclin-1 upregulation and frequent granula-tion of LC3.CONCLUSION: Endoplasmic reticulum stress mediates ox-LDL-induced autophagy in macrophages , and moderates activation of autophagy may protect macrophages from ox-LDL-induced apoptosis by inhibiting CHOP expression .

Objective:To investigate the effect of the timing of continuous renal replacement therapy (CRRT) administration on the prognosis of acute kidney injury (AKI) in children.Methods:The medical records of children with AKI who were admitted to the Intensive Care Unit of Hunan Children′s Hospital from March 2015 to February 2020 and underwent CRRT were prospectively analyzed.The children who met the criteria were divided into early group (defined as AKI 1 and 2) and delayed group (defined as AKI 3) according to AKI stage.The general conditions, indicators when CRRT was initiated, and prognosis of the children in two groups were recorded.Results:(1) A total of 39 children were included in the study, including 23 in the early group and 16 in the delayed group.There were no significant differences in age, gender, body weight and proportion of mechanical ventilation between two groups ( P>0.05). The score of critical cases in the early group was higher than that in the delayed group ( P=0.008). (2) There were no significant differences in serum potassium and bicarbonate when CRRT was initiated between two groups ( P>0.05). The urine output in the early group was higher than that in the delayed group ( P>0.001). The serum creatinine and urea nitrogen in the early group were lower than those in the delayed group ( P>0.05). (3) The 28-day survival rate and proportion of renal function recovery at 28 days in the early group were significantly higher than those in the delayed group ( P>0.05). The duration of CRRT, ICU stay and duration of mechanical ventilation in the early group were shorter than those in the delayed group ( P>0.05). Conclusion:Early initiation of CRRT at AKI stage 1 and 2 can improve the 28-day survival rate and renal function recovery of survivors when critically ill children are complicated with AKI.

Objective:To investigate the clinical value of serum cystatin C(Cys C) and neutrophil gelatinase associated lipocalin(NGAL) combined with cardiac biomarkers in the evaluation of sepsis with renal injury in children.Methods:The clinical data of 130 children with sepsis(67 cases in sepsis non AKI group and 63 cases in septic AKI group)admitted to pediatric intensive care unit(PICU) at Hunan Children′s Hospital from May 2018 to December 2019 were retrospectively analyzed.The differences of serum Cys C, NGAL and cardiac related biomarkers between sepsis and septic kidney injury were analyzed and compared.Results:The levels of serum Cys C, NGAL and amino-terminal pro-brain natriuretic peptide(NT-proBNP) in children with septic AKI were significantly higher than those in children of sepsis non AKI group(all P<0.01). There were no significant differences in creatine kinase isoenzyme(CK-MB)and high-sensitivity troponin T(cTnT-hs) between two groups (all P>0.05). The levels of CK-MB, cTnT-hs, NT-proBNP, Cys C and NGAL in the dead children were significantly higher than those in the surviving children ( P<0.05). In terms of predicting of AKI, the area under the ROC curve of NGAL, Cys C and NT proBNP were 0.724, 0.759 and 0.747, respectively.Regarding predicting the survival and death of sepsis, the area under the ROC curve of NGAL, Cys C and NT proBNP were 0.719, 0.722 and 0.769, respectively.In predicting the prognosis of children with sepsis and kidney injury, the area under the ROC curve of NGAL, Cys C and NT proBNP were 0.683, 0.651 and 0.682, respectively.The binary Logistic regression equation was established by Cys C, NGAL and NT-proBNP, Y=0.970 NGAL+ 0.9441 BNP+ 1.815 Cys C-2.944.In predicting kidney injury, evaluating prognosis of sepsis and predicting prognosis of sepsis with kidney injury, the area under ROC curve of new variable Y were 0.882, 0.802 and 0.808, respectively. Conclusion:NGAL, Cys C and NT-proBNP can be used to judge sepsis and sepsis with kidney injury alone.The evaluation value of combined detection of three indexes is better than that of single index.Therefore, the combined use of the three indicators may be better to judge the condition of children with sepsis and kidney injury.

Objective:To investigate the predictive value of sputum heparin binding protein(HBP) in sepsis related acute respiratory distress syndrome(ARDS).Methods:This study was a prospective case-control study.A total of 134 children with sepsis who were admitted in PICU at Hunan Children′s Hospital from January 2020 to November 2021 were included, including 63 children who had completed fiberoptic bronchoscopy.The 63 children were divided into sepsis without ARDS group, sepsis with mild ARDS group, and sepsis with moderate to severe ARDS group according to the presence and severity of ARDS.Sputum was collected and HBP was detected in all children with sepsis when they were admitted to the hospital.The alveolar lavage fluid within 72 hours of admission was reserved for HBP.The levels of interleukin (IL)-6 and tumor necrosis factor (TNF)- α were detected, and the blood biochemistry, pulmonary imaging, pediatric critical case score and other data within 72 hours were collected.Results:(1) Among 63 children with fiberoptic bronchoscopy, 29 were in sepsis without ARDS group, 18 were in the sepsis with mild ARDS group, and 16 were in the sepsis with moderate to severe ARDS group.There was no significant difference in the pediatric critical case score and the location of primary infection focus among the three groups at admission.The primary infection focus was respiratory system in 36 cases, whose sputum HBP level was (42.1±9.8) ng/mL, and 27 children with other systems infection, whose sputum HBP level was (37.8±10.8) ng/mL, there was no significant difference between two groups ( t=1.65, P=0.104). (2) There were significant differences in sputum HBP, alveolar lavage fluid HBP, IL-6 and TNF-α levels among sepsis with mild ARDS group, sepsis with moderate and severe ARDS group and sepsis without ARDS group ( P<0.05). The sputum HBP of 34 children with sepsis combined with ARDS was positively correlated with alveolar lavage fluid HBP, IL-6, TNF-α levels and lung injury score, and negatively correlated with SpO 2/FiO 2 ( P<0.05). (3)Among the 34 children with sepsis combined with ARDS, the sputum HBP concentration of children with invasive ventilation was significantly higher than that of children with non-invasive ventilation ( P<0.05). The sputum HBP concentration in children with three or more organ damage was significantly higher than that of children with two or less organ damage ( P<0.05). The sputum HBP concentration of dead children was higher than that of surviving children ( P<0.05). (4) The area under curve of sputum HBP for predicting ARDS was 0.772 (95% CI: 0.655~0.889). When the cut-off point value of sputum HBP was 27.9 mU/L, whose sensitivity and specificity were 70.6% and 79.3%, respectively.The area under curve of sputum HBP for predicting moderate and severe ARDS was 0.793 (95% CI: 0.661~0.926). When the cut-off point value of sputum HBP was 51.55 mU/L, whose sensitivity and specificity were 81.3% and 76.6%, respectively. Conclusion:Sputum HBP is elevated in children with sepsis and ARDS, which is related with the severity of the disease.Sputum HBP has a good predictive value for the diagnosis and severity of children with sepsis and ARDS, and can be used as a clinically effective and convenient evaluation index for children with sepsis related ARDS.

Objective:To investigate the value of the ratio of heparin binding protein (HBP) to albumin (ALB) in diagnosis and predict the severity of Kawasaki disease shock syndrome (KDSS).Methods:This study was a retrospective study. Pediatric patients with Kawasaki disease (KD) admitted to the Children's Intensive Care Unit and department of Pediatric Emergency Center of Hunan Children's Hospital from January 2019 to May 2022 were enrolled. The HBP/ALB ratio was calculated according to HBP and serum ALB. The children were divided into three groups (low, medium, and high ratio groups) according to the median and upper and lower quartiles of the HBP/ALB ratio. The differences of each index among the three groups were compared. The receiver operating characteristic curves were drawn to evaluate the clinical value of the HBP/ALB ratio in diagnosis of KDSS and the severity of the disease.Results:A total of 111 cases were included in this study, including 28 cases in the low ratio group, 56 cases in the medium ratio group, and 27 cases in the high ratio group. There were 24 cases with coronary artery damage, 87 cases without coronary artery damage, 27 cases with abnormal ECG findings, and 17 children with KDSS (including 5 cases in the medium ratio group, and 12 cases in the high ratio group). The incidence of KDSS, coronary involvement, and abnormal electrocardiogram proportions in the high ratio group were significantly higher than those in the other two groups. Compared with low and medium ratio groups, the levels of cardiac troponin I, N-terminal pro-brain natriuretic peptide, lactate, stroke output variation, trends in thoracic fluid content, white blood cell count, C-reactive protein, procalcitonin, and D-dimer levels were higher in the high ratio group, while ALB and blood sodium levels were lower in the high ratio group (all P<0.05). There was no significant difference in above indicators between the low and medium ratio groups (all P>0.05). The HBP/ALB ratio had a higher area under the curve, sensitivity, and specificity (0.942, 0.882, and 0.883, respectively) in predicting KDSS compared to HBP alone (0.776, 0.842, and 0.670, respectively). Conclusion:The HBP/ALB ratio could reflect the severity of children with KD and has certain clinical value for prognostic evaluation.

Objective:To investigate the efficacy and safety of dexmedetomidine in noninvasive continuous positive airway pressure(NCPAP)for acute respiratory failure in children.Methods:Clinical data of children with acute respiratory failure who underwent NCPAP from January 2018 to March 2020 in PICU of Hunan Children′s Hospital were prospectively collected.They were randomly divided into dexmedetomidine group(group D)and midazolam group(group M), with a total of 100 children.We compared the sedation depth of the two groups at 7 time points after sedation at 0.5 h(t1), 1 h(t2), 2 h(t3), 6 h(t4), 12 h(t5), 24 h(t6), and 48 h(t7), time to reach proper sedation, NCPAP time, NCPAP failure rate, oxygenation index(P/F value)before sedation(T0)and 1h(T1), 24h(T2), and 48h(T3)after sedation, and the main vital signs and adverse reactions before sedation(T0)and 1h(T1), 24h(T2), 48h(T3)after sedation.Results:(1)The proportion of proper sedation at T4, T5, T6 and T7 after sedation in group D was higher than that in group M[98%(49/50)vs.84%(42/50), 94%(47/50)vs.90%(45/50), 96%(48/50)vs.88%(44/50), 90%(45/50)vs.88%(44/50), χ2=6.538, 8.043, 8.174, 7.678, all P<0.05]. Time to reach proper sedation in group D was shorter[(58.6±7.9)s vs.(66.7±9.3)s, t=4.682, P<0.01]. (2)The treatment time and failure rate of NCPAP in group D were lower than those in group M[(134.9±25.5)h vs.(147.8±24.3)h, 10%(5/50)vs.28%(14/50), all P<0.05]. P/F after NCPAP treatment in the two groups was improved as compared with that before treatment(all P<0.01), and the improvement was more significant in group D than in group M at T2 and T3 after sedation[(199.3±26.1)vs.(188.5±24.2)mmHg, (212.2±25.4)mmHg vs.(200.8±24.8)mmHg, t=2.132, 2.278, all P<0.05]. (3)There were no significant differences in heart rate(HR), mean arterial pressure(MAP), and respiratory rate(RR)before sedation between the two groups(all P>0.05). HR and RR after sedation in both groups decreased as compared with those before sedation( P<0.01). HR at T1, T2, and T3 after sedation in group D decreased more significantly than that in group M[(116.3±17.6)bpm vs.(124.8±14.1)bpm, (110.2±18.4)bpm vs.(121.9±15.2)bpm, (108.5±18.7)bpm vs.(117.6±12.8)bpm, t=0.479, -3.474, -2.840, all P<0.05]. There was no significant difference in RR after sedation between the two groups( t=1.872, 1.632, 1.675, all P>0.05). MAP at T1 in group D decreased as compared with T0( P<0.01). MAP at T1 in group D was lower than that in group M[(65.5±5.1)mmHg vs.(68.0±5.7)mmHg, t=-2.297, P=0.024]. (4)There was no significant difference in the incidence of total adverse reactions between the two groups[20%(10/50)vs.14%(7/50), P=0.595]. The incidence of bradycardia was higher in group D than in group M[16%(8/50)vs.2%(1/50), P=0.031]. Conclusion:The incidence of adverse reactions of dexmedetomidine and midazolam in the sedation of NCPAP in children with acute respiratory failure is similar, but the sedative effect of dexmedetomidine is better than that of midazolam in the improvement of pulmonary oxygenation.

Objective:To investigate the efficacy and safety of bronchoscopic lavage in children with severe adenoviral pneumonia.Methods:Patients with severe adenovirus pneumonia who were admitted to ICU department of Hunan Children′s Hospital for bronchoscopy were collected from February to June 2019 and divided into lavage group( n=36) and non-lavage group( n=15) in line with whether lavage was performed.Their results, namely, bronchoscopic diagnosis, blood gas analysis before and 2 hours, 24 hours and 48 hours after bronchoscopy, improvement time of clinical symptoms(fever and pulmonary moist rales), the positive rate of pathogen detection and mortality rate, main vital signs such as heart rate, respiratory rate, mean arterial pressure and bronchoscopy-related complications were recorded before and 1 hour, 2 hours and 24 hours after bronchoscopy. Results:A total of 51 children were collected, all of whom suffered from endobronchitis.More secretions were observed in the airways of 36 patients in the lavage group, and only a little or no secretions were observed in 15 patients in the non-lavage group.P/F value and PCO 2 at 2 hours, 24 hours and 48 hours after treatment in the lavage group were improved comparing to those before treatment and were superior to those in the non-lavage group( P<0.05). P/F values at 24 hours and 48 hours after treatment in the non-lavage group increased and PCO 2 decreased at 48 hours after treatment( P<0.05). The thermal duration, time to resolution of moist rales in the lungs in the lavage group were shorter than those in the non-lavage group( P<0.05). The mortality rate in the lavage group was lower than that in the non-lavage group[2.8%(1/36) vs.26.7%(4/15), P<0.05]. The positive rate of pathogen detection in lavage group was higher than that in non-lavage group[55.6%(20/36) vs. 20.0%(3/15), P<0.05]. There was no significant difference in heart rate, respiratory rate, and mean arterial pressure at each time point before and after bronchoscopic treatment( P>0.05). Associated complications were 11 cases of intraoperative transient hypoxemia, four cases of bronchial mucosal bleeding, and one case each of postoperative hypoxemia, intraoperative hypertension and hypotension.There was no significant difference in the incidence of complications between the two groups( P>0.05). Conclusion:Bronchoscopic lavage, in treating children with severe adenovirus pneumonia, may improve clinical symptoms, respiratory function, and rate of pathogen detection, reduce mortality, and is effective and safe.