Advances in neutrophil extracellular traps in bronchopulmonary dysplasia / 国际儿科学杂志

Due to the development of neonatal intensive care, the survival rate of very preterm infants and very low birth weight infants has been significantly improved, and the incidence of bronchopulmonary dysplasia (BPD) has been obviously increasing year by year.The pathogenesis of BPD has not been clear, it is considered that inflammation is an important link in the occurrence and development of BPD at present.Neutrophils can use their neutrophil extracellular traps (NETs) to capture and kill pathogens and reduce inflammation, but excessive formation of NETs is easy to induce inflammatory imbalance, so as to damage normal cells or tissues and participate in the pathophysiological process of BPD.This paper reviews the structure, formation, function and regulatory role of NETs in BPD, and the targeted treatment strategies and potential research directions of NETs in BPD.

Analysis of risk factors of mortality in infants and toddlers with moderate to severe pediatric acute respiratory distress syndrome / 中华儿科杂志

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ2=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ2=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ2=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.

Diagnosis and treatment of pediatric septic shock in pediatric intensive care units from hospitals of different levels / 中华儿科杂志

Objective: To investigate the differences in clinical characteristics, diagnosis, and treatment of pediatric septic shock in pediatric intensive care unit (PICU) among hospitals of different levels. Methods: This retrospective study enrolled 368 children with septic shock treated in the PICU of Beijing Children's Hospital, Henan Children's Hospital, and Baoding Children's Hospital from January 2018 to December 2021. Their clinical data were collected, including the general information, location of onset (community or hospital-acquired), severity, pathogen positivity, consistence of guideline (the rate of standard attainment at 6 h after resuscitation and the rate of anti-infective drug administration within 1 h after diagnosis), treatment, and in-hospital mortality. The 3 hospitals were national, provincial, and municipal, respectively. Furthermore, the patients were divided into the tumor group and the non-tumor group, and into the in-hospital referral group and the outpatient or emergency admission group. Chi-square test and Mann-Whitney U test were used to analyze the data. Results: The 368 patients aged 32 (11, 98) months, of whom 223 were males and 145 females. There were 215, 107, and 46 patients with septic shock, with males of 141, 51, and 31 cases, from the national, provincial, and municipal hospitals, respectively. The difference in pediatric risk of mortality Ⅲ (PRISM Ⅲ) scores among the national,provincial and municipal group was statistically significant (26(19, 32) vs.19(12, 26) vs. 12(6, 19), Z=60.25,P<0.001). The difference in community acquired septic shock among the national,provincial and municipal group was statistically significant (31.6%(68/215) vs. 84.1%(90/107) vs. 91.3%(42/46), χ2=108.26,P<0.001). There were no significant differences in compliance with guidelines among the 3 groups (P>0.05). The main bacteria detected in the national group were Klebsiella pneumoniae (15.4% (12/78)) and Staphylococcus aureus (15.4% (12/78)); in the provincial group were Staphylococcus aureus (19.0% (12/63)) and Pseudomonas aeruginosa (12.7% (8/63)), and in the municipal group were Streptococcus pneumoniae (40.0% (10/25)) and Enteric bacilli (16.0% (4/25)). The difference in the proportion of virus and the proportion of 3 or more initial antimicrobials used among the national,provincial and municipal group was statistically significant (27.7% (43/155) vs. 14.9% (13/87) vs. 9.1% (3/33), 22.8%(49/215) vs. 11.2%(12/107) vs. 6.5%(3/46), χ2=8.82, 10.99, both P<0.05). There was no difference in the in-hospital mortality among the 3 groups (P>0.05). Regarding the subgroups of tumor and non-tumor, the national group had higher PRISM Ⅲ (31(24, 38) vs. 22 (21, 28) vs.16 (9, 22), 24 (18, 30) vs. 17(8, 24) vs. 10 (5, 16), Z=30.34, 10.45, both P<0.001), and it was the same for the subgroups of in-hospital referral and out-patient or emergency admission (29 (21, 39) vs. 23 (17, 30) vs. 15 (10, 29), 23 (17, 29) vs. 18 (10, 24) vs. 11 (5, 16), Z=20.33, 14.25, both P<0.001) as compared to the provincial and municipal group. There was no significant difference in the in-hospital mortality among the 2 pairs of subgroups (all P>0.05). Conclusion: There are differences in the severity, location of onset, pathogen composition, and initial antibiotics of pediatric septic shock in children's hospitals of different levels, but no differences in compliance with guidelines and in-hospital survival rate.

Clinical and molecular characteristics of Streptococcus pneumoniae-associated hemophagocytic lymphohistiocytosis in children / 中华儿科杂志

Objective: To summarize the clinical features of Streptococcus pneumoniae-associated hemophagocytic syndrome (SP-HLH), and the serotypes and drug-resistant characteristics of the isolated strains. Methods: There were 15 children with SP-HLH admitted to the Pediatric Intensive Care Unit (PICU) of Beijing Children's Hospital, Capital Medical University from January 2013 to December 2020 were included in this study. Clinical data including children's general characteristics, clinical features, laboratory examinations, treatments, prognosis and the outcomes of follow-up by May 2021 were analyzed retrospectively. The serotypes and drug resistance of the isolated strains were identified. All children were divided into the clinical improvement group and the death group. Mann-Whitney U test, Fisher's exact test were used to compare the data of the two groups. Results: Among the 15 children with SP-HLH, 8 were males and 7 were females. The age of these children was 1.0 (1.0, 2.5) years. Regarding the primary infection, there were 9 cases of severe pneumonia, 3 cases of meningitis and 3 cases of blood stream infection. None of these children had received pneumoniae conjugate vaccine (PCV) and all of them were admitted to the PICU. Respiratory failure was observed in 10 patients, acute renal injury in 5, and hemolytic uremic syndrome in 3 patients. All children received glucocorticoids and high-dose intravenous immunogloblin (IVIG) in addition to anti-infective treatment. Eight of the children were cured while the other 7 died. The neutrophil count in the death group was lower than that in the clinical improvement group ((5.0 (1.7, 9.3) × 109 vs. 5.2 (3.4, 10.5) ×109/L, Z =-2.43, P<0.015), and the length of hospital stay and days of PICU stay in the death group were both shorter than those in the improvement group statistically (3 (1, 11) vs. 39 (34, 48) d, 2 (1, 4) vs. 19 (12, 31) d, Z=-3.25, -3.24, both P=0.001). Ten serotypes of Streptococcus pneumoniae were identified, including 4 strains of 19F, 3 of 19A, 1 of 23F, 1 of 15A and 1 of 14, among which 9 strains (9/10) were covered by PCV13. All strains were resistant to erythromycin yet sensitive to vancomycin and linezolid. Conclusions: SP-HLH is more common in children under the age of 3, with a high mortality rate. The death cases have lower neutrophil count and rapid disease progression. The comprehensive treatment is anti-infective combined with glucocorticoids and high-dose IVIG. The predominant serotypes are 19F and 19A and all isolated strains were susceptible to vancomycin and linezolid.

Effect and influence factors of cardiopulmonary resuscitation in children with congenital heart disease in pediatric intensive care unit / 中华儿科杂志

Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ2=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ2=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.

Clinical analysis of 6 critically ill children with acute chlorine poisoning / 中华儿科杂志

Objective: To analyze the clinical characteristics and treatment of critically ill children with acute chlorine poisoning and explore the risk factors and effective strategies. Methods: This retrospective study collected the clinical data, including general state, clinical characteristics, treatment and follow-up(till 1 year and 6 months after discharge), of 6 critically ill children who were hospitalized in the Pediatric Intensive Care Unit of Beijing Children's Hospital due to acute chlorine poisoning in August 2019. Results: There were 6 children characterized by severe dyspnea in this accident, among whom 4 were boys and two girls, aged 4-12 years. When the accident occurred, they were within 5 m of the chlorine source. These patients underwent tracheal intubation and mechanical ventilation in 3.5-7.0 h after poisoning. The child who was the closest to the chlorine source (1.5 m) and took the longest time (5 min) to evacuate was the most severe one. He suffered hypoxia which could not be corrected by conventional mechanical ventilation and severe shock, then had veno-arterial extracorporeal membrane oxygenation(ECMO) treatment started 10 h after the accident. All the 6 children in this study survived. Following-up found no growth and developmental abnormality. The pulmonary function tests were normal except for one case with increased small airway resistance due to previous suspected asthma, and the lung CT, electhoencephalogram, and brain magnetic resonance imaging were all normal. Conclusions: Severe chlorine poisoning is mainly characterized by respiratory failure. Mechanical ventilation is often required within a few hours after poisoning. When conventional mechanical ventilation is ineffective, ECMO could save live. Timely treatment could improve prognosis.

Methodology of Differentiation of Bone Marrow Cells into Megakaryocytes in Vitro / 中国实验血液学杂志

OBJECTIVE@#To explore the method for inducing the differentiation of bone marrow cells into megakaryocytes in vitro so as to use for evaluating the activity of traditional Chinese medicines.@*METHODS@#The bone marrow cells were separated from femurs and tibias of mice. The experiments were divided into 4 groups: control (no adding cytokines), TPO (adding 50 ng/ml TPO), TPO+SCF (50 ng/ml+50 ng/ml) and TPO+SCF+IL-6+IL-9 (50 ng/ml+50 ng/ml+20 ng/ml+20 ng/ml). The bone marrow cells in 4 groups were cultured in vitro for 6 d. Then the cell growth status was observed by the inverted microscopy, and the cell count was detected by using the automatic cell counter. The ratio and absolute count of megakaryocytes were detected by flow cytometry.@*RESULTS@#Compared with control, three induction methods could stimulate the differentiation of bone marrow cells into megakaryocytes in vitro. TPO could slightly enhance the differentiation of bone marrow cells into megakaryocytes. Both the combination of TPO and SCF, and the combination of TPO, SCF, IL-6 and IL-9 could intensively stimulate proliferation of bone morrow cells and promote the differentiation of bone marrow cells into megakaryocytes. The addition of IL-6 and IL-9 could decrease the proliferation of non-megakaryocytes, but promote the differentiation of bone marrow cells into megakaryocytes.@*CONCLUSION@#The optimized differentiation of bone marrow cells into megakaryocytes has been completed by co-induction regimen of TPO, SCF, IL-6 and IL-9, which can be used to screen and evaluate traditional Chinese medicines promoting formation of platelets.

Lagged effect of temperature on non-accidental mortality and years of life lost in Wuxi: a time-series study / 中华疾病控制杂志

Objective To evaluate the effect of air temperature on non-accidental mortality (A00-R99) and years of life lost in Wuxi city. Methods Data on daily non-accidental mortality and meteorology index were collected from 2012 to 2017. Distributed lag non-linear model (DLNM) was used to assess the effect of temperature on non-accidental death and YLL and the cumulative effects between cold and hot temperature on non-accidental mortality and years of life lost with different lag days. Results A V-shaped relationship was noticed between temperature and mortality. Cold effects were delayed by 3 days and persisted for 14 days. Hot effects appeared acute and reached the peak at the same day. Low temperature had stronger gross effect than high temperature had. There were differences of temperature effects between different age and gender groups. Conclusions Low and high temperature were associated with elevated mortality risk. Cold effect had lagged effect and persisted for long time, however, hot effects appeared acute and the impact of low temperature was greater.

Non-Invasive Ventilation in Children with Paediatric Acute Respiratory Distress Syndrome

INTRODUCTION@#Evidence supporting non-invasive ventilation (NIV) in paediatric acute respiratory distress syndrome (PARDS) remains sparse. We aimed to describe characteristics of patients with PARDS supported with NIV and risk factors for NIV failure.@*MATERIALS AND METHODS@#This is a multicentre retrospective study. Only patients supported on NIV with PARDS were included. Data on epidemiology and clinical outcomes were collected. Primary outcome was NIV failure which was defined as escalation to invasive mechanical ventilation within the first 7 days of PARDS. Patients in the NIV success and failure groups were compared.@*RESULTS@#There were 303 patients with PARDS; 53/303 (17.5%) patients were supported with NIV. The median age was 50.7 (interquartile range: 15.7-111.9) months. The Paediatric Logistic Organ Dysfunction score and oxygen saturation/fraction of inspired oxygen (SF) ratio were 2.0 (1.0-10.0) and 155.0 (119.4- 187.3), respectively. Indications for NIV use were increased work of breathing (26/53 [49.1%]) and hypoxia (22/53 [41.5%]). Overall NIV failure rate was 77.4% (41/53). All patients with sepsis who developed PARDS experienced NIV failure. NIV failure was associated with an increased median paediatric intensive care unit stay (15.0 [9.5-26.5] vs 4.5 [3.0-6.8] days; <0.001) and hospital length of stay (26.0 [17.0-39.0] days vs 10.5 [5.5-22.3] days; = 0.004). Overall mortality rate was 32.1% (17/53).@*CONCLUSION@#The use of NIV in children with PARDS was associated with high failure rate. As such, future studies should examine the optimal selection criteria for NIV use in these children.

Celastrus orbiculatus Extracts Inhibit Human Hepatocellular Carcinoma Growth by Targeting mTOR Signaling Pathways / 中国结合医学杂志

OBJECTIVE@#To characterize the molecular mechanism underlying the antineoplastic activity of Celastrus orbiculatus Thunb. extracts (COE).@*METHODS@#The human hepatocellular carcinoma HepG2 cells with mammalian target of rapamycin (mTOR) knockdown expressed (HepG2/mTOR) were constructed using molecular biological technology. In vitro, the HepG2/mTOR cells were treated with COE at various concentrations (10, 20, 40, 80, 160 and 320 µ g/mL). Cell viability was determined using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays. According to the half-maximal inhibitory concentration (IC) value (140 mg/L), the concentrations of COE in the subsequent experiment was set to alleviate cytotoxicity. The HepG2/mTOR cells were divided into 5 groups: negative control (untreated), COE treatment groups (40, 80, 120 mg/L COE) and positive control group (cisplatin, DDP, 2 mg/L), respectively. Wild-type HepG2 cells were used as a blank control. The effects of COE on the cell apoptosis were analyzed by flow cytometry and transmission electronic microscopy (TEM), respectively. The protein expression levels of mTOR signal pathways were determined by Western blotting. In vivo, HepG2/mTOR cells (2 × 10 cell/mice) were subcutaneously injected into the right flank of nude mice. Thirty-six female nude mice were randomly assigned to 6 groups according to body weight (6 mice per group) as follows: solvent vehicle control, Banmao Capsule treated group (BM, 195 mg/kg), Tegafur, Gimeracil and Oteracil Potassium Capsules (10 mg/kg) treated group, and different dosages of COE (10, 20, 40 mg/kg) groups. Tumor growth was monitored and immunohistochemical staining was used to examine the expression of apoptosis-related proteins in tumor tissues.@*RESULTS@#COE inhibited the proliferation significantly in a concentration-dependent manner in HepG2/mTOR cells (P<0.01). COE significantly induced the apoptosis of HepG2/mTOR cells (P<0.01), and the apoptotic bodies can be observed under TEM. COE significantly inhibits the proteins expression of mTOR-related signal pathways. In vivo, COE significantly inhibited tumor growth in nude mice (P<0.01). Moreover, the results showed that COE down-regulated the expression of Bcl-2 and Bcl-xL, and up-regulated the levels of Bax and caspase-3 protein (P<0.01).@*CONCLUSION@#COE was a potential chemotherapeutic drug in HCC treatments via targeting mTOR signal pathway.

Extracts of Celastrus Orbiculatus Inhibit Cancer Metastasis by Down-regulating Epithelial-Mesenchymal Transition in Hypoxia-Induced Human Hepatocellular Carcinoma Cells / 中国结合医学杂志

OBJECTIVE@#To evaluate the effects of Celastrus Orbiculatus extracts (COE) on metastasis in hypoxia-induced hepatocellular carcinoma cells (HepG2) and to explore the underlying molecular mechanisms.@*METHODS@#The effect of COE (160, 200 and 240 µ g/mL) on cell viability, scratch-wound, invasion and migration were studied by 3-4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide (MTT), scratch-wound and transwell assays, respectively. CoCl was used to establish a hypoxia model in vitro. Effects of COE on the expressions of E-cadherin, vimentin and N-cadherin were investigated with Western blot and immunofluorescence analysis, respectively.@*RESULTS@#COE inhibited proliferation and metastasis of hypoxia-induced hepatocellular carcinoma cells in a dose-dependent manner (P<0.01). Furthermore, the expression of epithelial-mesenchymal transition (EMT) related markers were also remarkably suppressed in a dose-dependent manner (P<0.01). In addition, the upstream signaling pathways, including the hypoxia-inducible factor 1 α (Hif-1 α) and Twist1 were suppressed by COE. Additionally, the Hif-1 α inhibitor 3-5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), potently suppressed cell invasion and migration as well as expression of EMT in hypoxia-induced HepG2 cells. Similarly, the combined treatment with COE and YC-1 showed a synergistic effect (P<0.01) compared with the treatment with COE or YC-1 alone in hypoxia-induced HepG2 cells.@*CONCLUSIONS@#COE significantly inhibited the tumor metastasis and EMT by suppressing Hif-1 α/Twist1 signaling pathway in hypoxia-induced HepG2 cell. Thus, COE might have potential effect to inhibit the progression of HepG2 in the context of tumor hypoxia.

Association of copy number of SMN1 and SMN2 with clinical phenotypes in children with spinal muscular atrophy / 中国当代儿科杂志

OBJECTIVE@#To study the association of copy number of SMN1 and SMN2 with clinical phenotypes in children with spinal muscular atrophy (SMA).@*METHODS@#A total of 45 children with SMA were enrolled. Multiplex ligation-dependent probe amplification was used to measure the gene copy numbers of SMN1 and SMN2. The association of copy number of SMN1 and SMN2 with clinical phenotypes was analyzed.@*RESULTS@#Of the 45 children with SMA, 42 (93%) had a homozygous deletion of SMN1 exons 7 and 8, and 3 (7%) had a deletion of SMN1 exon 7 alone. No association was found between SMA clinical types and the deletion types of SMN1 exons 7 and 8 (P>0.05). There was a significant difference in the distribution of SMN2 gene copy numbers between the children with SMA and the healthy children (P<0.05). The children with SMA usually had two or three copies of SMN2 gene, while the healthy children usually had one or two copies of SMN2 gene. There was a significant difference in the distribution of SMN2 copy numbers among the children with different SMA clinical types (P<0.05). The children with two copies of SMN2 gene had a significantly lower age of onset than those with three or four copies. Most of the children with type I SMA had two or three copies of SMN2 gene. Most of the children with type II SMA had three copies of SMN2 gene. Most of the children with type III SMA had three or four copies of SMN2 gene. Children with a higher copy number of SMN2 gene tended to have an older age of onset and better motor function and clinical outcome, and there was a significant association between SMN2 gene copy number and clinical outcome (P<0.05).@*CONCLUSIONS@#The SMN2 gene can reduce the severity of SMA via the dosage compensation effect. SMN2 copy number is associated with the phenotype of SMA, and therefore, it can be used to predict disease severity.

Blood purification therapy for sepsis / 中国实用儿科杂志

Sepsis is a life-threatening organ dysfunction caused by the body's dysfunctional response to infection. There is currently no definitive symptomatic treatment for sepsis inflammatory response in the clinic. Blood purification treatment exerts immunomodulatory effects by non-specifically eliminating endotoxin and/or inflammatory mediators and shows a good prospect of application in sepsis. However,most studies on the treatment of sepsis with blood purification have not shown significant improvement in patients' prognosis. This article reviews the research progress of immunoregulation mechanism of blood purification therapy for sepsis,as well as the advantages and disadvantages of different blood purification methods.

Relationship between chronic renal injury and white matter hypertensity, enlarged perivascular spaces in elderly patients / 临床神经病学杂志

Objective To study the relationship between chronic renal injury and white matter hypertensity (WMH), enlarged perivascular spaces (EPVS) in elderly patients.Methods A total of 133 inpatients from 2015 to 2016 without clinical histories of stroke underwent brain MRI scan were enrolled.The degree of WMH and EPVS were evaluated according to Flair and T 2 MRI, respectively.Clinical characteristics including disease history , glomerular filtration rate ( eGFR), urine albumine／creatine ratio ( UACR ) and so on were compared between different degrees of WMH or EPVS.A logistic regression analysis was applied for further analysis.Results Compared with WMH scoring 0 -1 group, eGFR of WMH scoring 2 -3 group was significantly decreased , while UACR was significantly increased ( all P＜0.001).Compared with EPVS scoring 0 -1 group, eGFR of EPVS scoring 2-3 group was significantly decreased , while UACR was significantly increased (all P＜0.001).Logistic regression analysis showed that low eGFR and high UACR were independent risk factors for WMH and EPVS (all P＜0.05).Conclusion Chronic renal injury could be the independent risk factor of higher degree of WMH and EPVS , which would be potential for clinical use.

Expression of long-chain non-coding RNA-LINC00485 in lung cancer and its effect on proliferation and migration of lung cancer cells / 临床与实验病理学杂志

Purpose To observe the expression of longchain non-coding RNA-LINC00485 (LINC00485) in lung cancer cell lines and tissues, and to investigate its effect on the proliferation and migration of lung cancer cells and its mechanism.Methods Quantitative real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect differential expression of LINC00485 in four lung cancer cell lines (H1975, A549, HCC827, H1299), normal alveolar epithelial cells HPAEPIC, and in 12 cases lung cancer tissues and adjacent tissues. Bioinformatics methods were used to predict the microRNA (miRNA) that LINC00485 may bind and target gene that miRNA may bind. Small interfering RNAs (siRNAs) that target silencing LINC00485 were transfected into HCC827 cells by liposomes.The expression levels of LINK00485, miR-361-5p, and p21 activated protein kinase 2 (PAK2) mRNA were detected by qRTPCR. The expression level of PAK2 protein was detected by Western blot. The cell proliferation ability was measured by MTS assay. Cell scratch assay was used to detect cell migration. Results Compared with normal alveolar epithelium, LINC00485 was highly expressed in lung cancer cell lines (P < 0.05), and the expression level was highest in HCC827 cells. The expression of LINC00485 in lung cancer tissues was higher than that in adjacent tissues (P < 0.01). After down-regulation of LINC00485 expression in HCC827 cells, the expression of miR-361-5p was up-regulated (P < 0.01), the expression of PAK2 mRNA and protein was down-regulated (P < 0.01), the proliferative capacity of HCC827 cells was decreased (P < 0.05), and the ability of cell migration was decreased (P < 0.01).Conclusion The expression of LINC00485 is increased in lung cancer cell lines and tissues. Down-regulation of LINC00485 can inhibit the proliferation and migration of lung cancer HCC827 cells by regulating the expression of miR-361-5p and PAK2 genes.

Imaging Gliomas with Nanoparticle-Labeled Stem Cells / 中华医学杂志(英文版)

<p><b>Objective:</b>Gliomas are the most common neoplasm of the central nervous system (CNS); however, traditional imaging techniques do not show the boundaries of tumors well. Some researchers have found a new therapeutic mode to combine nanoparticles, which are nanosized particles with various properties for specific therapeutic purposes, and stem cells for tracing gliomas. This review provides an introduction of the basic understanding and clinical applications of the combination of stem cells and nanoparticles as a contrast agent for glioma imaging.</p><p><b>Data Sources</b>Studies published in English up to and including 2017 were extracted from the PubMed database with the selected key words of "stem cell," "glioma," "nanoparticles," "MRI," "nuclear imaging," and "Fluorescence imaging."</p><p><b>Study Selection:</b>The selection of studies focused on both preclinical studies and basic studies of tracking glioma with nanoparticle-labeled stem cells.</p><p><b>Results:</b>Studies have demonstrated successful labeling of stem cells with multiple types of nanoparticles. These labeled stem cells efficiently migrated to gliomas of varies models and produced signals sensitively captured by different imaging modalities.</p><p><b>Conclusion</b>The use of nanoparticle-labeled stem cells is a promising imaging platform for the tracking and treatment of gliomas.</p>

Dynamic visual analysis of neutrophils chemotaxis in peritoneal cavity of schizophrenic model in mice / 北京大学学报(医学版)

OBJECTIVE@#To compare the differences of neutrophils chemotaxis ability in peritoneal cavity between normal rats and schizopherenic rats with cell dynamic visualization system.@*METHODS@#In the study,18 healthy Kunming rats were randomly divided into 3 groups which were control group (n=6), 0.3 mg/kg MK-801 treatment group (n=6), 0.6 mg/kg dizocilpine maleate (MK-801) treatment group(n=6), extracted neutrophils separately, and observed the morphology and counted under a microscope. Each group of cells was divided into two parts for chemotactic experiment, called chemokine agent treatment group and no chemokine agent treatment group respectively, indicating control 1, 0.3 mg/kg MK-801 treatment 1,0.6 mg/kg MK-801 treatment 1 and control 2, 0.3 mg/kg MK-801 treatment 2,0.6 mg/kg MK-801 treatment 2. The dynamic migration of cells was recorded using the NIS-Elements software, and TAXIScan Analyzer 2 software was used to select 30 cells (n=30) in each group of cells and analyze cells migration trajectory, speed and distance, and use pair test and One-Way analysis of variance for statistical analysis.@*RESULTS@#The number of neutrophils in control group, 0.3 mg/kg MK-801 treatment group and 0.6 mg/kg MK-801 treatment group were(1.00±0.03)×104/mL,(0.05±0.02)×104/mL,(0.32±0.01)×104/mL respectively, the differences of results were statistically significant(P<0.05).Under the effect of chemotactic agent,the directional migration capability of neutrophils in control group 1, 0.3 mg/kg MK-801 treatment group 1 and 0.6 mg/kg MK-801 treatment group 1 were(0.85±0.11) radian,(1.00±0.11) radian,(0.96±0.10) radian respectively (P<0.05); the migration velocities of neutrophils were (0.09±0.02) μm/s,(0.12±0.01) μm/s,(0.14±0.01) μm/s respectively (P<0.05);the migration distances of neutrophils were (94.26±0.02) μm,(134.61±0.01) μm,(156.19±0.01) μm respectively(P<0.05).@*CONCLUSION@#Compared with neutrophils in peritoneal cavity of control group, the neutrophils in peritoneal cavity of schizophrenic rats have stronger chemotactic movement ability.

Application of anoptomagnetic probe Gd-DO3A-EA-FITC in imaging and analyzing the brain interstitial space / 北京大学学报(医学版)

OBJECTIVE@#To investigate the application of the optical magnetic bimodal molecular probe Gd-DO3A-ethylthiouret-fluorescein isothiocyanate (Gd -DO3A-EA-FITC) in brain tissue imaging and brain interstitial space (ISS).@*METHODS@#In the study, 24 male SD rats were randomly divided into 3 groups, including magnetic probe group (n=6), optical probe group (n=6) and optical magnetic bimodal probe group (n=12), then the optical magnetic bimodal probe group was divided equally into magnetic probe subgroup (n=6) and optical probe subgroup (n=6). Referencing the brain stereotaxic atlas, the coronal globus pallidus as center level, the probes including gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA), fluorescein isothiocyanate (FITC) and Gd-DO3A-EA-FITC of 2 μL (10 mmol/L) were injected into the caudate nucleus respectively, magnetic resonance imaging (MRI) was performed in the magnetic probe group and magnetic probe subgroup to image the dynamic diffusion and distribution of the probes in the brain ISS, a self-developed brain ISS image processing system was used to measure the diffusion coefficient, clearance, volume fraction and half-time in these two groups. Laser scanning confocal microscope (LSCM) was performed in vitro in the optical probe group and optical probe subgroup for fluorescence imaging at the time points 2 hours after the injection of the probe, and the distribution in the oblique sagittal slice was compared with the result of the first two groups.@*RESULTS@#For the magnetic probe group and magnetic probe subgroup, there were the same imaging results between the probes of Gd-DTPA and Gd-DO3A-EA-FITC. The diffusion parameters of Gd-DTPA and Gd-DO3A-EA-FITC were as follows: the average diffusion coefficients [(3.31±0.11)×10-4 mm2/s vs. (3.37±0.15)×10-4 mm2/s, t=0.942, P=0.360], the clearance [(3.04±0.37) mmol/L vs. (2.90±0.51) mmol/L, t=0.640, P=0.531], the volume fractions (17.18%±0.14% vs. 17.31%±0.15%, t=1.961, P=0.068), the half-time [(86.58±3.31) min vs. (84.61±2.38) min, t=1.412, P=0.177], the diffusion areas [(23.25±0.68) mm2 vs. (22.71±1.00) mm2, t=1.100, P=0.297]. The statistical analysis of each brain was made by t test, and the diffusion parameters were not statistically significant. Moreover, for the optical probe group and optical probe subgroup, the diffusion area of Gd-DO3A-EA-FITC [(22.61±1.16) mm2] was slightly larger than that of FITC [(22.10±1.29) mm2], the statistical analysis of each brain was made by t test, and the diffusion parameters were not statistically significant (t=0.713, P=0.492).@*CONCLUSION@#Gd-DO3A-EA-FITC shows the same imaging results as the traditional GD-DTPA, and it can be used in measuring brain ISS.

Celastrus orbiculatus extracts inhibit invasion and metastasis in human hepatocellular carcinoma HepG2 cells by targeting mTOR / 中草药

Objective To investigate the molecular mechanisms of Celastrus orbiculatus extracts (COE) of the invasion and metastasis inhibition in human hepatocellular carcinoma HepG2 cells by targeting mTOR. Methods The HepG2/mTOR- cells with mTOR knockout expression were constructed by using siRNA technology. The effect of COE on the proliferation of the HepG2/mTOR- cells was also studied. The HepG2/mTOR- cells were treated with COE in different concentrations (20, 40, 80, 160, and 320 mg/L) for 24 h. The cell reproductive capability of HepG2/mTOR- cells was detected by MTT. The effect of COE on the metastatic ability of HepG2/mTOR- cells in vitro was investigated by scratch assay and Transwell migration assay. The expression levels of molecular mechanisms related proteins MMP-2 and MMP-9 were assessed by Western blotting. Results The HepG2/mTOR- cells with mTOR knockout expression were successfully constructed. COE significantly inhibited the proliferation of HepG2/mTOR- cells in a concentration-dependent manner (P < 0.05). COE decreased the invasion and migration of HepG2/mTOR- cells. The results of Transwell experiment indicated that COE (80 mg/L) significantly reduced the number of transmembrane cells (P < 0.05). And the expression levels of MMP2 and MMP9 protein were significantly reduced in the HepG2/mTOR- cells after the treatment of COE. Conclusion COE can significantly inhibit the proliferation, invasion, and migration in the HepG2/mTOR- cells. Our data reveal that COE is a potential chemotherapeutic drug in human hepatocellular carcinoma treatments via targeting mTOR signal pathway.

An Analysis of Risk Factors of Renal Inadequacy after Postpartum Hemorrhage / 昆明医科大学学报

Objective To investigate the risk factors of renal inadequacy after postpartum hemorrhage. Methods According to the diagnostic criteria of postpartum hemorrhage, 200 cases of postpartum hemorrhage who were admitted to the Intensive Care Unit from January 2010 to December 2014 were collected. The general situation, history of pregnancy induced hypertension and gestational diabetes mellitus, ASA classification, anesthesia method, delivery mode, postpartum hemorrhage and other indicators. The risk factors were analyzed by logistic regression.Results Among 200 cases of postpartum hemorrhage who were admitted in the intensive care unit, 21 cases with renal insufficiency were seenafter delivery (10.5%) aged between 20 and 44 years old with the average age of (29.24 ±4.58) years old. Using the ASA evaluation criteria to evaluate the preoperative situation, we observed179 cases in ASA grade levelⅠ (89.5%), 20 casesin level Ⅱ (10%), one casein level Ⅲ (0.5%) and no case in grade Ⅳ. Among all the women, we found 147 cases of vaginal delivery (73.5%), 53 cases of cesarean section (26.5%),196 cases of spinal anesthesia (including labor analgesia) (98%) and 4 casesof general anesthesia (2%) . There were 12 patients with hypertension during pregnancy (6%), and 188 patients without hypertension (94%) . There were 9 cases of gestational diabetes mellitus (4.5%), and 191patients without gestational diabetes mellitus (95.5%).Conclusions The risk factors of renal insufficiency after postpartum hemorrhage were: age older than 35 years, cesarean delivery, pregnancy history of hypertension or gestational diabetes mellitus.