The value of bedside ultrasound and biomarkers in the diagnosis of sepsis-induced myocardial dysfunction and prognosis of septic shock in children / 中国小儿急救医学

Objective:To evaluate the feasibility of using bedside ultrasound and serum biomarkers for the prediction of sepsis-induced myocardial dysfunction(SIMD)and mortality in septic shock patients.Methods:The patients diagnosed as septic shock were enrolled in the study from January 2019 to July 2021 in PICU at Shanghai Children′s Medical Center Affiliated to Shanghai Jiaotong University School of Medicine.Bedside ultrasound results were recorded at day 1, 2, 3, 7 and 10.Blood samples were collected at the same time, markers of myocardial injury were detected, and prognosis was recorded at 28 days.According to the left ventricular ejection fraction (LVEF), children with septic shock were divided into SIMD group and non-SIMD group.Those with LVEF <50% or decreased by ≥10% from baseline level were defined as SIMD.Differences in cardiac ultrasound parameters and biomarkers between two groups were compared.Logistic regression analysis was performed to determine the independent risk factors for SIMD and the independent risk factors for death at 28 days after septic shock.The area under the receiver operating characteristic curve (AUC) was used to evaluate the efficacy of different indicators in predicting SIMD and the death outcome of children with septic shock on 28 days.Results:A total of 57 children were enrolled, including 28 cases in SIMD group and 29 cases in non-SIMD group.Univariate analysis showed that there were statistically significant differences in pediatric critical illness score, N-terminal B-type natriuretic peptide(NT-proBNP), LVEF and left ventricular short axis shortening rate between two groups ( P<0.05). Logistic analysis demonstrated that LVEF( OR=0.890, 95% CI 0.818-0.969, P=0.007)and NT-proBNP ( OR=1.000, 95% CI 1.000-1.000, P=0.015)could independently predict SIMD.There were 42 cases in survival group and 15 in non-survival group according to the prognosis on 28 days.Univariate analysis showed that there were significant differences in pediatric risk mortality score Ⅲ, pediatric sequential organ failure assessment, cardiac troponin I, and mitral annular plane systolic excursion(MAPSE)( P<0.05). Logistic analysis showed that only MAPSE independently predicted mortality( OR=85.670, 95% CI 1.685-4 356.736, P=0.026). Compared with MAPSE(AUC=0.727), MAPSE combined with pediatric risk mortality score Ⅲ, pediatric sequential organ failure assessment, cardiac troponin I(AUC=0.926) could be better to predict the 28 days prognosis of patients with septic shock on 28 days. Conclusion:NT-proBNP increases significantly in the early stage of SIMD.MAPSE shows no difference between SIMD and non-SIMD patients.MAPSE is correlated with the prognosis of patient with septic shock.

Combination antibiotic therapy in PICU / 中国小儿急救医学

Combination antibiotic therapy is one of the strategies for use of antibiotics in clinic.Currently, high-quality clinical studies supporting combination therapy are rare and contradictory.This review summarized the indications, types, advantages and disadvantages of combination antibiotic therapy, novel combination therapies and recommended antibiotic therapy for the patients with sepsis.

Clinical characteristics of 17 critically ill children with severe adverse reactions after chimeric antigen receptor T cells therapy / 中国小儿急救医学

Objective:To investigate the clinical characteristics, treatment process and prognosis of children with severe side effects after chimeric antigen receptor T cell immunotherapy(CAR-T), so as to provide evidence for timely intervention after CAR-T treatment.Methods:From June 1, 2015 to May 31, 2020, children with cytokine release syndrome(CRS)or immune cell related neurotoxicity syndrome(ICANS)who were treated with CAR-T therapy in our hospital and revealed severe effects transferred to PICU were included in the study, and their clinical course and multiple laboratory examination data were systematically analyzed.Results:Seventeen children showed CRS reaction and entered PICU after CAR-T therapy.The most common clinical symptoms were respiratory distress(13 cases) and circulatory disorder(10 cases), of which 7 cases were complicated with severe ICANS.Serum interferon -γ(IFN-γ)and interleukin-6(IL-6)levels significantly increased after CAR-T cell infusion, reaching the peak at (5.1±1.6)days.The serum levels of IFN-γ and IL-6 in children with severe CRS were significantly higher than those in children with mild CRS(all P<0.05). The level of serum IL-6 in children with high tumor load was significantly higher than that in children with low tumor load( P<0.05). The mortality rate of children with elevated level of serum TNF-α was higher(5/5 vs.3/11, P<0.05). Children with severe CRS were more likely to develop grade 4 ICANS(4/4 vs.0/3, P<0.05). The mortality rate of children with oxygenation index(P/F value)<200 mmHg(1 mmHg=0.133 kPa) was higher(5/5 vs.2/12, P<0.05). The vasoactive inotropic score[ M( Min, Max)] in the death group was significantly higher than that in survival group[29.5(14.0, 50.0) vs.1.5(0, 25.0), Z=8.000, P=0.027]. Conclusion:Serum IL-6 and IFN-γ are crucial causes of CRS.High tumor load is one of the factors causing high level of serum inflammatory factors.Respiration and circulation systems are the most frequently involved systems.Therefore, the evaluation indexes of these two systems can help us judge the prognosis of children.

An email-based survey of treatment strategies in children with septic shock in China / 中国小儿急救医学

Objective:To describe the treatment strategies in children with septic shock in China.Methods:A questionnaire was prepared and 368 pediatric intensivists from the Pediatric Critical Care Physician Branch of Chinese Medical Doctor Association were surveyed about the treatment of pediatric septic shock from April to June 2017.Results:Surveys were received from 87.2%(68/78) institutions and 368 questionnaires (response-rate 45.1%) were included.59.2% and 77.7% of the respondents chose debridement surgery and fluid drainage as source control intervention.Antibiotics were used within 1 hour of shock in 90.8% of respondents.98.4% of respondents chose normal saline, 72.3% of respondents chosen albumin, and 53.8% of respondents chosen plasma for fluid resuscitation.When no venous access was available during shock resuscitation, 57.1% of respondents preferred intraosseous access.79.3% and 83.2% of the respondents used the adjuvant therapy such as glucocorticoids and intravenous immunoglobulin.96.7%, 85.3% and 22.0% of respondents were likely to provide oxygen and mechanical ventilation, continuous renal replacement, and extracorporeal membrane oxygenation as organ support, respectively.Additionally, 322 (88.7%), 188 (51.1%), and 85 (23.1%) respondents chose the "best advice" options to simulated clinical cases of fluid resuscitation, inotropic agents, and vasoactive agents, respectively.In the simulated cases of vasoactive drugs and inotropic drugs, 69.3% and 24.2% of the respondents chose fluid resuscitation strategy, respectively.In cases of fluid resuscitation, 49.7% (183/368) of respondents reported performing fluid responsiveness and volume status assessment, and instruments used in the assessment included bedside echocardiography[39.4% (145/368)], bioreactance[10.3% (38/368)], transpulmonary thermodilution devices[6.3% (23/368)]. Pediatricians who received advanced life support courses for children ( P=0.006) and intensive care specialist training center training ( P=0.002) were more likely to choose the " best recommendation" option than those who did not attend the training. Conclusion:The current status of pediatric septic shock treatment strategies in China are active source control intervention, antibiotic use and organs support, and increased awareness of non-invasive hemodynamic monitoring.However, there may be excessive fluid infusion and inappropriate use of plasma, glucocorticoids and intravenous immunoglobulin.Different training and continuing education may improve rational treatment strategies.

Clinical characteristics and prognosis of severe pneumocystis carinii pneumonia in pediatric liver transplant recipients / 中国小儿急救医学

Objective:To analyze the clinical characteristics and risk factors for mortality of severe pneumocystis carinii pneumonia(PCP)in pediatric liver transplant(LT)recipients.Methods:The data of severe PCP in LT recipients diagnosed at Shanghai Children′s Medical Center from November 2019 to February 2021 were collected.The clinical characteristics and risk factors for 28-day mortality were analyzed.Results:Fifteen patients were enrolled in the study.Thirteen cases survived and 2 cases were non-survived.There was no routine anti-pneumocystis prophylaxis after LT.The median age of onset of PCP was 12(7, 26)months.The median time after LT was 3.00(0.33, 4.00)months.The onset clustered in November-December and June-August.All patients were mechanically ventilated, and some patients were given prone ventilation(11 cases), neuromuscular blocking agents(13 cases)and high concentration oxygen(more than 60%, nine cases). Fourteen cases were complicated with other infections.Two cases were complicated with pneumothorax and subcutaneous/mediastinal emphysema.There were 2 cases with septic shock-like manifestation, 1 case of right heart insufficiency, 1 case of right heart failure(death), and 1 case of multiple organ failure(death). Compared with the survived group, the non-survived group had higher pediatric risk of mortality Ⅲ score[3.5(0.0, 6.0)vs.8.5(5.0, 12.0), Z=1.993, P=0.046] and lactate dehydrogenase level[1 731.5(1 012.0, 3 270.0)U/L vs.4 387.5(3 606.0, 5 169.0)U/L, Z=2.148, P=0.032]. Conclusion:PCP in pediatric LT is critical and complicated.Pediatric risk of mortality Ⅲ scores and lactate dehydrogenase increase in 28-day hospitalized deaths.

Clinical characteristics and prognosis of severe pneumocystis carinii pneumonia in pediatric liver transplant recipients / 中国小儿急救医学

Objective:To analyze the clinical characteristics and risk factors for mortality of severe pneumocystis carinii pneumonia(PCP)in pediatric liver transplant(LT)recipients.Methods:The data of severe PCP in LT recipients diagnosed at Shanghai Children′s Medical Center from November 2019 to February 2021 were collected.The clinical characteristics and risk factors for 28-day mortality were analyzed.Results:Fifteen patients were enrolled in the study.Thirteen cases survived and 2 cases were non-survived.There was no routine anti-pneumocystis prophylaxis after LT.The median age of onset of PCP was 12(7, 26)months.The median time after LT was 3.00(0.33, 4.00)months.The onset clustered in November-December and June-August.All patients were mechanically ventilated, and some patients were given prone ventilation(11 cases), neuromuscular blocking agents(13 cases)and high concentration oxygen(more than 60%, nine cases). Fourteen cases were complicated with other infections.Two cases were complicated with pneumothorax and subcutaneous/mediastinal emphysema.There were 2 cases with septic shock-like manifestation, 1 case of right heart insufficiency, 1 case of right heart failure(death), and 1 case of multiple organ failure(death). Compared with the survived group, the non-survived group had higher pediatric risk of mortality Ⅲ score[3.5(0.0, 6.0)vs.8.5(5.0, 12.0), Z=1.993, P=0.046] and lactate dehydrogenase level[1 731.5(1 012.0, 3 270.0)U/L vs.4 387.5(3 606.0, 5 169.0)U/L, Z=2.148, P=0.032]. Conclusion:PCP in pediatric LT is critical and complicated.Pediatric risk of mortality Ⅲ scores and lactate dehydrogenase increase in 28-day hospitalized deaths.

Non-biological artificial liver technology in the treatment of early liver allograft dysfunction in 2 children with liver transplantation / 中华实用儿科临床杂志

The clinical data of 2 children with early graft liver dysfunction (EAD) admitted to the Pediatric Intensive Care Unit, Shanghai Children′s Medical Center, Shanghai Jiaotong University School of Medicine were retrospectively analyzed to discussed the therapeutic significance of non-biological artificial liver technology, such as intermittent plasma exchange (PE) combined with continuous veno-venous hemodiafiltration (CVVHDF) in children with EAD.Case 1 was suffering from biliary atresia, and case 2 was suffering from Niemann-Pick disease.Graft liver dysfunction and multiple organ dysfunction occurred in 2 children after liver transplantation.PE and CVVHDF were initiated early in the first two days after liver transplantation.After one-week therapy with intermittent PE plus CVVHDF, acute multiple organ dysfunction were reversed with liver function remarkably improved in the 2 cases.Therefore non-biological artificial liver technique can be tried after liver transplantation in children.This technique contributes to the recovery of liver function and can improve the secondary multi-organ insufficiency.

Whole lung lavage in an infant with pulmonary alveolar proteinosis and literature review / 中华儿科杂志

Objective@#To investigate the safety, feasibility and operation key points of whole lung lavage in infants with pulmonary alveolar proteinosis.@*Methods@#The clinical manifestations, genetic screening, therapeutic interventions and outcome of an infant with pulmonary alveolar proteinosis complicated with respiratory failure who received whole lung lavage in November 2018 in Shanghai Children′s Medical Center Affiliated to Shanghai Jiaotong University School of Medicine were reported. Websites including PubMed, Springer Link, China National Knowledge Infrastructure (CNKI), Weipu Database, and Wanfang Database were searched using the key words of "whole lung lavage" "pediatric" and "pulmonary alveolar proteinosis" for articles published from their establishments to April 2019. Relevant literature was reviewed.@*Results@#A 3-month-old boy had experienced cough, shortness of breath and cyanosis for 1 week prior to admission to pediatric intensive care unit. Physical examination showed hepatosplenomegaly. Complete blood cell count showed mild anemia (hemoglobin 96 g/L) and normal white blood cells. The patient had normal C-reactive protein and normal blood platelet. Biochemical panel showed hypoalbuminemia (31 g/L), mildly elevated glutamic oxaloacetic transaminase (115 U/L) and blood ammonia (165 μmol/L), extremely elevated lactate dehydrogenase (>6 600 U/L) and hyperferritinemia (>4 500 μg/L). Chest computed tomography (CT) revealed decreased transmittance of both lungs, patchy high density shadow and ground glass opacity. Genetic testing revealed a mutation of c.625+1G>A in SLC7A7. Schiff reaction (PAS staining) in bronchoalveolar lavage fluid was positive. The patient was diagnosed with severe pneumonia, respiratory failure, lysinuria urinary protein intolerance, and pulmonary alveolar proteinosis. The patient received sequential unilateral whole lung lavage in 2 days and was successfully weaned from ventilator. He was discharged home breathing room air. Eleven articles (11 in English and non in Chinese) were reviewed. Twenty-one patients were included. After whole lung lavage, 76% (16/21) of the patients had improvement in respiratory function.@*Conclusions@#Whole lung lavage can effectively improve respiratory failure caused by pulmonary alveolar proteinosis in infant patients. The procedure is feasible and safe.

Highly sensitive serological approaches for Pepino mosaic virus detection / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Pepino mosaic virus (PepMV) causes severe disease in tomato and other Solanaceous crops around globe. To effectively study and manage this viral disease, researchers need new, sensitive, and high-throughput approaches for viral detection. In this study, we purified PepMV particles from the infected Nicotiana benthamiana plants and used virions to immunize BALB/c mice to prepare hybridomas secreting anti-PepMV monoclonal antibodies (mAbs). A panel of highly specific and sensitive murine mAbs (15B2, 8H6, 23D11, 20D9, 3A6, and 8E3) could be produced through cell fusion, antibody selection, and cell cloning. Using the mAbs as the detection antibodies, we established double antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA), Dot-ELISA, and Tissue print-ELISA for detecting PepMV infection in tomato plants. Resulting data on sensitivity analysis assays showed that both DAS-ELISA and Dot-ELISA can efficiently monitor the virus in PepMV-infected tissue crude extracts when diluted at 1:1 310 720 and 1:20 480 (weight/volume ratio (w/v), g/mL), respectively. Among the three methods developed, the Tissue print-ELISA was found to be the most practical detection technique. Survey results from field samples by the established serological approaches were verified by reverse transcription polymerase chain reaction (RT-PCR) and DNA sequencing, demonstrating all three serological methods are reliable and effective for monitoring PepMV. Anti-PepMV mAbs and the newly developed DAS-ELISA, Dot-ELISA, and Tissue print-ELISA can benefit PepMV detection and field epidemiological study, and management of this viral disease, which is already widespread in tomato plants in Yunnan Province of China.

Efficacy and safety of tranexamic acid in total hip arthroplasty via direct anterior approach / 中国骨伤

OBJECTIVE@#To evaluate the efficacy and safety of local application of tranexamic acid (TXA) in reducing perioperative blood loss in total hip arthroplasty via direct anterior approach (DAA).@*METHODS@#From July 2013 to September 2018, 46 patients with avascular necrosis of the femoral head were divided into tranexamic acid group (@*RESULTS@#The incision healed well and no obvious complications occurred in the two groups. All patients were followed up for 12 to 59 months(averaged 31.11 months). No hip pain was found in the follow-up patients. Hip joint function was improved effectively and no prosthesis loosening occurred. The total perioperative blood loss in tranexamic acid group and normal saline group was(740.09±77.14) ml and (1 069.07±113.53) ml respectively, 24 hours after operation, the drainage volume was (87.61±9.28) ml, (233.83±25.62) ml, the hidden blood loss was (409.65±38.01) ml and (588.33±57.16) ml. the difference of hemoglobin before and after operation was (24.78±2.19) g / L and (33.57±2.95) g / L, the difference was statistically significant (@*CONCLUSION@#local application of tranexamic acid in total hip arthroplasty through direct anterior approach can safely and effectively reduce perioperative blood loss, and does not increase the risk of thrombosis, and does not affect the normal recovery of joint function.

The prognostic value of Th1/Th2 cytokines on septic children with or without neutropenia / 中华急诊医学杂志

Objective To explore the characteristics and value for predicting prognosis of cytokines in septic children with or without neutropenia.Methods Totally 138 septic children were divided into the neutropenia and non-neutropenia groups according to absolute neutropenic count.Septic children were divided into the shock and non-shock groups according to circulation function and organ perfusion.The levels of C-reactive protein,procalcitonin,cytokines,PRISM-Ⅲ and clinical outcomes were analyzed between the relative groups.Results (1) Totally 138 septic children were recruited,64 with neutropenia and 74 without neutropenia.The level of PRISM-Ⅲ of the neutropenia group was significantly higher than that of the non-neutropenia group (P=0.048).Mortality showed no significant difference between the two groups,but hospital stay in the neutropenia group was longer than that in the non-neutropenia group.The levels of C-reactive protein,IL-6,and IL-10 ihe neutropenia group were significantly higher than those of the non-neutropenia group (P=0.001;P=0.001;P=0.032).The level of TNF-α in the neutropenia group was significantly lower than that of the non-neutropenia group (P=0.032).(2)Among the 64 septic children with neutropenia,23 were combined with shock.The PRISM-Ⅲ level of the shock group was significantly higher than that of the non-shock group (P=0.001).The mortality of the shock group (43.5％,10/23) was significantly higher than the non-shock group (2.4％,1/41) (P=0.001).C-reactive protein,procalcitonin,IL-6,IL-10 and TNF-α in the shock group elevated obviously than those in the non-shock group (P=0.001;P=0.001;P=0.001;P=0.005;P=0.019).The area under receiver operating characteristic curve was 0.8 for IL-6 (cut-offvalue 315.38 pg/mL),0.8 for IL-10 (cutoff value 45.18 pg/mL),and 0.85 for TNF-α (cut-off value 1.95 pg/mL).(3) Among the 74 septic children without neutropenia,19 were combined with shock The PRISM-Ⅲ level of the shock group was significantly higher than that of the non-shock group (P=0.022).There was no significant difference of mortality between the two groups (P=0.3).IL-10 level in the shock group elevated obviously than that in the non-shock group (P=0.015).(4) Among the 42 children with sepsis shock,23 were combined with neutropenia.The PRISM-Ⅲ level of the neutropenia group was significantly higher than that of the non-neutropenia group (P=0.005).There was no significant difference of mortality between the two groups (P=0.29).The levels of C-reactive protein,procalcitonin,IL-6 and IL-10 in the neutropenia group were significantly higher than those in the non-neutropenia group (P=0.001;P=0.001;P=0.001;P=0.035).There was no difference of TNF-α level between the two groups.(5) Among the 96 children without sepsis shock,41 were combined with neutropenia.No difference of PRISM-Ⅲ level was observed between the neutropenia and nonneutropenia groups.The mortality of the neutropenia group was significantly lower than that in the non-neutropenia group (2.4％ vs 20％,P=0.02).The levels of C-reactive protein and IL-6 in the neutropenia group were significantly higher than those in the non-neutropenia group (P=0.005;P=0.033).The TNF-α level was significantly lower than that in the non-neutropenia group (P=0.007).Conclusions Compared to children without neutropenia,septic children combined with neutropenia have longer hospital stay,and septic shock children combined with neutropenia have higher mortality,and levels of IL-6,IL-10 and TNF-α were also significantly increased.The levels of IL-6,IL-10 and TNF-α can help to predict prognosis of children with sepsis.

Phospholipidomics study of Jiegeng Decotion for LPS-induced acute lung injury in mice based on UHPLC-Q-Exactive Orbitrap/MS / 药学学报

Using the lipidomics method based on UHPLC-Q-Exactive Orbitrap/MS, the change of phospholipid metabolism in lung tissue of mice induced by lipopolysaccharide (LPS)-induced acute lung injury was analyzed to observe the regulation of abnormal lipids by Jiegeng Decoction and to explore the regulation effect of Jiegeng Decoction on LPS-induced acute lung injury. The lung tissue samples from control group, model group, dexamethasone (positive drug) group, and Jiegeng Decoction group were collected and the lipid components of the sample were extracted. All procedures over mice were performed in accordance with the Guidelines for Care and Use of Laboratory Animals of Nanjing University of Chinese Medicine, and the experiments were approved by the Animal Ethics Committee of our university. The lipidomics technique of UHPLC-Q-Exactive Orbitrap/MS was used to study change of phospholipids in lung tissue of each group. LPS induced acute lung injury in mice with metabolic abnormalities of phospholipids, the specific performance of the PC was significantly upregulated, phosphatidyl ethanolamine (PE), phosphatidyl glycerol (PG), phosphatidyl serine (PS),phosphatidylinositol (PI) and other metabolic disorders, Jiegeng Decoction have a certain role in these phospholipids. LPS-induced acute lung injury caused disturbances of phospholipid in vivo, and Jiegeng Decoction regulates metabolic phospholipids.

Metabolomics on Pudilan Xiaoyan Oral Liquid in treatment of Influenza A/H1N1-induced pneumonia based on GC-MS / 中草药

Objective To screen the pneumonia-related abnormal metabolites in lung tissue of mice infected by Influenza A/H1N1, and to monitor the regulation effect of Pudilan Xiaoyan Oral Liquid and to explore potential anti-pneumonia mechanism. Methods ICR mice were randomly divided into four groups with ten mice in each group: normal group, model group, Pudilan group, and Ribavirin group. The mice were infected with H1N1 virus intranasally and gavage once every-day for six consecutive days. 2 h after the last dose, the mice were sacrificed and lungs were collected. Metabolomics based on GC-MS was applied to analyze the changes of metabolites in the lung tissue of each group. The potential biomarkers of H1N1-induced pneumonia were screened by three conditions: P 1.0, and Fold Change > 1.5. Metabolic pathways related to the treatment mechanism of Pudilan Xiaoyan Oral Liquid were analyzed. Results The infection of H1N1 virus leads to infiltration of inflammatory cells in the lungs of mice and various degrees of pneumonitis and metabolic disorders. Pudilan Xiaoyan Oral Liquid and ribavirin can both ameliorate the symptoms of pneumonia and play role in callback of various metabolites. Conclusion The treatment effect of Pudilan Xiaoyan Oral Liquid on H1N1-induced pneumonia is related to the regulation effects on 14 potential biomarkers and 12 associated metabolic pathways.

Application of leukoreduction therapy in severe pertussis with leukocytosis and pulmonary hyperten-sion:3 infant cases reports and literatures review / 中国小儿急救医学

Objective To investigate the efficacy and safety of leukoreduction therapy in severe per-tussis in infants. Methods Therapeutic processes of 3 cases of severe pertussis in PICU of Shanghai Children′s Medical Center were retrospectively studied from October 2017 to May 2018. We reviewed the related literatures and summarized the time and effectiveness of leukoreduction therapy in severe pertussis. Results All 3 cases had leukocytosis,respiratory faliure,pulmonary hypertension and right heart failure. One case had multiple organ failure before undergoing exchange transfusion therapy and eventually died. Two cases that had pulmonary hypertension during the period of WBC′s rising accepted leukopheresis therapy before multiple organ failure,and eventually survived. We reviewed the foreign literatures which was almost case reports,leukoreduction therapy might improve the prognosis of severe pertussis in infants,but the time of using it had no conclusion. Conclusion This is the first report of leukoreduction therapy for the severe per-tussis in infants in China. It provides a new method for the treatment of severe pertussis in infants. It is worth looking forward to use this method combined with continuous renal replacement therapy and extracorporeal membrane oxygenation technology. In the future,multicenter clinical research should be done to explore the effectiveness and safety of leukoreduction therapy in the severe pertussis in infants.

Preliminary study of the expression of long chain non-coding RNA in sepsis children / 中国小儿急救医学

Objective To explore the expression and clinical value of long non-coding RNA ( lncRNA) in sepsis children. Methods The peripheral blood samples were analyzed from 15 sepsis children ( sepsis group) ,7 septic shock children( septic shock group) and 21 healthy children( healthy control group) . The real time-polymerase chain reaction was used to explore the expression of 9 kinds of lncRNA (AK092960,LOC100192426,VHDJH,AC006230. 3,AC019097. 7,RP4-652L8. 2,RP11-108A15. 2,NKILA and AK023660) which are closely related to the nuclear factor-κB pathway of the sepsis. And further analysis of lncRNA expression between sepsis,septic shock and health children were carried out. The specificity and sensitivity of the lncRNAs compared with C-reactive protein, procalcitonin and WBC for identification of patients with sepsis or septic shock were also evaluated. Results The expression of VHDJH,AC019097. 7, RP4-652L8. 2,RP11-108A15. 2, NKILA and AK02366 in the sepsis group were significantly higher than those in the healthy control group(P < 0.01). Among them,the expression of VHDJH,AC019097.7, RP4-652L8. 2,NKILA and AK023660 in the septic shock group were higher than those in the sepsis group (P<0. 01). Although the specificity and sensitivity of VHDJH, AC019097. 7, RP4-652L8. 2, NKILA and AK023660 were higher than C-reactive protein,procalcitonin and WBC for sepsis and septic shock,respectively, there was no significant difference statistically(P >0.05). Conclusion VHDJH,AC019097.7,RP4-652L8.2, RP11-108A15. 2,NKILA and AK023660 could be the potential diagnostic biomarkers of sepsis and might reflect its severity.

Rapamycin affect the apoptosis of splenic CD4+CD25+ regulatory T cells of mouse severe aplastic anemia model / 中华血液学杂志

Objective@#To explore the effects and possible mechanism of rapamycin (RAPA) on apoptosis of CD4+CD25+ Tregs from the mouse severe aplastic anemia (SAA) model.@*Methods@#The BALB/c female SAA model mice were induced by interferon-gamma in combination with busulphan. The SAA model mice were intraperitoneal injection with RAPA at daily dose of 0.5 mg/kg for 5 days (the RAPA-treated group, n=15) in the SAA group (n=15) and the un-treated group (n=15) were control. Bone marrow hematopoiesis changes were observed by the patho-morphological examination of femurs. The mononuclear cells of the peripheral blood and spleen were subjected to assess the intracellular Foxp3 expression in CD4+CD25+ Tregs by flow cytometry (FCM). In addition, after being pured by immunomagnetic beads, the splenic CD4+CD25+ Tregs was subjected to assess apoptosis by FCM and the Akt and Stat3 phosphorylation by using of western blot.@*Results@#The patho-morphological examination of femurs showed normal marrow cell proliferation in un-treated group and hypocellularity in both SAA group and RAPA-treat group, with an increase in the number of fat cells. The bone marrow hematopoietic tissue ratio in RAPA-treat group was higher than SAA group [(9.75±1.83)% vs (7.00±2.00)%, Δx=2.15% (95%CI 0.15%-5.35%), P=0.037]. In the SAA group, FCM analysis showed down-expression of Foxp3 in CD4+CD25+ Tregs compared with the un-treated group. However, after treatment with RAPA, the expression of Foxp3 in CD4+CD25+ Tregs was increased (P<0.017). Compared with the un-treated group, increased CD4+CD25+ Tregs apoptosis [(19.84±1.39)% vs (29.85±2.72)%] with increased Akt phosphorylation accompanied by increased Stat3 phosphorylation was found in SAA group (P<0.05, respectively). On the contrary, RAPA-treated group exhibited CD4+ CD25+ Tregs with a reduction in apoptosis rate [(22.39±3.71)%], Akt phosphorylation and Stat3 phosphorylation compared with the SAA group (P<0.05, respectively).@*Conclusion@#These results indicate that RAPA may increase the expression of Foxp3 by down-regulation the levels of Akt and Stat3 phosphorylation and reduce apoptosis in splenic CD4+CD25+ Tregs from the mice model of SAA.

Rapamycin affect the apoptosis of splenic CD4+CD25+ regulatory T cells of mouse severe aplastic anemia model / 中华血液学杂志

Objective: To explore the effects and possible mechanism of rapamycin (RAPA) on apoptosis of CD4+CD25+ Tregs from the mouse severe aplastic anemia (SAA) model. Methods: The BALB/c female SAA model mice were induced by interferon-gamma in combination with busulphan. The SAA model mice were intraperitoneal injection with RAPA at daily dose of 0.5 mg/kg for 5 days (the RAPA-treated group, n=15) in the SAA group (n=15) and the un-treated group (n=15) were control. Bone marrow hematopoiesis changes were observed by the patho-morphological examination of femurs. The mononuclear cells of the peripheral blood and spleen were subjected to assess the intracellular Foxp3 expression in CD4+CD25+ Tregs by flow cytometry (FCM). In addition, after being pured by immunomagnetic beads, the splenic CD4+CD25+ Tregs was subjected to assess apoptosis by FCM and the Akt and Stat3 phosphorylation by using of western blot. Results: The patho-morphological examination of femurs showed normal marrow cell proliferation in un-treated group and hypocellularity in both SAA group and RAPA-treat group, with an increase in the number of fat cells. The bone marrow hematopoietic tissue ratio in RAPA-treat group was higher than SAA group [(9.75±1.83)% vs (7.00±2.00)%, Δx=2.15% (95%CI 0.15%-5.35%), P=0.037]. In the SAA group, FCM analysis showed down-expression of Foxp3 in CD4+CD25+ Tregs compared with the un-treated group. However, after treatment with RAPA, the expression of Foxp3 in CD4+CD25+ Tregs was increased (P<0.017). Compared with the un-treated group, increased CD4+CD25+ Tregs apoptosis [(19.84±1.39)% vs (29.85±2.72)%] with increased Akt phosphorylation accompanied by increased Stat3 phosphorylation was found in SAA group (P<0.05, respectively). On the contrary, RAPA-treated group exhibited CD4+ CD25+ Tregs with a reduction in apoptosis rate [(22.39±3.71)%], Akt phosphorylation and Stat3 phosphorylation compared with the SAA group (P<0.05, respectively). Conclusion: These results indicate that RAPA may increase the expression of Foxp3 by down-regulation the levels of Akt and Stat3 phosphorylation and reduce apoptosis in splenic CD4+CD25+ Tregs from the mice model of SAA.

Eeffect of HMGB1 on expression of NF-κB in BV-2 cells stimulated with Aβ25-35 / 中国病理生理杂志

AIM:To investigate the effect of high mobility group box-1 protein (HMGB1) on the expression of nuclear factor-κB ( NF-κB) in BV-2 cells stimulated with amyloid β-protein ( Aβ) 25-35 .METHODS:Cultured BV-2 cells in logarithmic growth phase were divided into 4 groups:normal cell group ( without any treatment ) , model group ( treated with Aβ25-35 at 40 μmol/L) , RNA interference ( RNAi) group ( conducted with HMGB1-siRNA followed by Aβ25-35 stimula-tion) and solvent control group (treated with 0.1% DMSO).After treatment with Aβ25-35 for 24 h, the protein levels of HMGB1 and NF-κB in BV-2 cells were determined by Western blot .RESULTS:Aβ25-35 at 40μmol/L was used to stimu-late BV-2 cells.The GFP fluorescence-tagged HMGB1-siRNA (30 nmol/L) was used to transfect BV-2 cells and its trans-fection efficiency was about 80%~90%.The results of Western blot showed that the protein level of HMGB 1 was signifi-cantly decreased after the interference of siRNA fragment (P<0.05).The protein levels of HMGB1 and nucleic NF-κB p65 were dramatically increased in BV-2 cells stimulated with Aβ25-35(P<0.05).After RNA interference with HMGB1, the expression of HMGB1 and nucleic NF-κB p65 were significantly decreased in BV-2 cells stimulated with Aβ25-35 ( P<0. 05).CONCLUSION:RNA interference with HMGB1 reduces the expression of nucleic NF-κB in BV-2 cells stimulated with Aβ25-35 .

Postoperative intensive care management in children with liver transplantation / 中国小儿急救医学

After half a century of development,liver transplantation has become an important means to solve the problem of end-stage liver diseases and has greatly improved the prognosis of the patients.This article reviewed and summarized the post-operation intensive care management and treatment of complication in children with liver transplantation.

Clinical study of thromboelastography for assessment of coagulation disorders in children with sepsis / 中华急诊医学杂志

Objective To study the clinical significance of thromboelastography (TEG) for determining the presence of coagulation disorders in septic children.Methods A total of 100 patients suffering from sepsis or severe sepsis in pediatric intensive care unit (PICU) of Shanghai Children's Medical Center from February 2014 to January 2015 were recruited.TEG tests and conventional coagulation laboratory tests (CCTs) including platelet count,fibrinogen,prothrombin time (PT),activated partial thromboplastin time,D-dimers,and international normalized ratio (INR) were carried out in all patients at the primary diagnosis of sepsis.Another 25 healthy children taking physical examination were enrolled as control group.Rank Sum Test was used to detect the differences in coagulation markers and TEG between the groups and there was statistical significance when P ＜ 0.05.Receiver operating characteristic (ROC) curves were used to evaluate the roles of TEG and CCTs tests in this study.Results Of them,there were 56 patients with sepsis and 44 with severe sepsis.The male to female ratio was 63∶ 37,the median age was 11.5 (3.3-48) months,and 71％ patients suffered from underlying disease.According to TEG,72 patients had coagulation disorders,including 28 with hypercoagulation and 44 with hypocoagulation.CCTs tests showed 50 patients had coagulation disorders,including 29 with non-overt DIC and 21 with overt DIC.The rate of hypercoagulability was significantly higher in non-DIC group than in non-overt DIC group (46％vs.17.2％,P =0.016).The rate of hypocoagulability was significantly higher in overt DIC group than in non-overt DIC group (100％ vs.44.8％,P ＜ 0.01).Patients with hypercoagulation disorders had significantly shorter R (coagulation reaction time) and K (coagulation formation time) and greater α (angle α),MA (maximal amplitude) and CI (comprehensive coagulation index) compared with control group (P ＜ 0.01).According to CCTs results,patients with hypercoagulation had significantly prolonged PT compared with control group (P =0.002).Compared with sepsis group,severe sepsis group had significantly prolonged R and K and lower α,MA and CI (P ＜ 0.01).ROC analysis demonstrated that area under the curve (AUC) of TEG and CCTs variables for diagnosis of severe sepsis were significantly greater than 0.5.Both variables of α (P =0.000 2) and K (P =0.004 1) had significantly greater AUCs compared with Fib.Conclusions There were 72％ septic patients with coagulation disorders.The hypercoagulability occurred earlier in patients with sepsis and the hypocoagulability occurred later in patients with severe sepsis.The TEG may provide important information for clinicians to deal with coagulation disorders in septic children.