Pharmacokinetics and pharmacodynamics of antibiotics in septic children treated with extracorporeal membrane oxygenation / 中华儿科杂志

Objective: To investigate the characteristics of pharmacokinetic (PK) and pharmacodynamic (PD) parameters of antibacterial agents in children with sepsis treated by extracorporeal membrane oxygenation (ECMO). Methods: In this prospective cohort study, 20 children with sepsis (confirmed or suspected) who were treated with ECMO and antimicrobial in the Department of Critical Medicine of Hunan Children's Hospital from March 2021 to December 2022 were enrolled as the ECMO group. Through therapeutic drug monitoring (TDM), the PK-PD parameters of antibacterial agents were analyzed. Twenty five children with sepsis in the same department who were treated with vancomycin but no ECMO at the same time were enrolled as the control group. The individual PK parameters of vancomycin were calculated by Bayesian feedback method. The PK parameters in the two groups were compared, and the correlation between trough concentration and area under the curve (AUC) was analyzed. Wilcoxon rank sum test was used for inter group comparison. Results: Twenty patients in the ECMO group, included 6 males and 14 females, with an onset age of 47 (9, 76) months. In the ECMO group, 12 children (60%) were treated with vancomycin, and the trough concentration was less than 10 mg/L in 7 cases, 10-20 mg/L in 3 cases, and >20 mg/L in 2 cases; AUC/minimum inhibitory concentration (MIC) (MIC=1 mg/L)<400 was in 1 case, 400-600 in 3 cases, and >600 in 8 cases. Among the 11 children (55%) who were treated with β-lactam antibiotics, there were 10 cases with drug concentration at 50% dosing interval (CT50)>4 MIC and 9 cases with trough concentration>MIC, both CT50 and trough concentration of cefoperazone reached the target. Among the 25 cases of control group, 16 were males and 9 females, with an onset age of 12 (8, 32) months. There was a positive correlation between vancomycin trough concentration and AUC (r2=0.36, P<0.001). The half-life of vancomycin and the 24-hour AUC (AUC0-24 h) in the ECMO group were higher than those in the control group (5.3 (3.6, 6.8) vs. 1.9 (1.5, 2.9) h, and 685 (505, 1 227) vs. 261 (210, 355) mg·h/L, Z=2.99, 3.50, respectively; both P<0.05), and the elimination rate constant and clearance rate was lower than those in the control group (0.1 (0.1, 0.2) vs. 0.4 (0.2, 0.5), 0.7 (0.5, 1.3) vs. 2.0 (1.1, 2.8) L/h, Z=2.99, 2.11, respectively; both P<0.05). Conclusion: The PK-PD parameters in septic children treated by ECMO varied with a longer half-life, higher AUC0-24 h, lower elimination rate constant and clearance rate.

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.

Research Progress of Breath Sound Analysis in Children with Bronchial Asthma / 中国医学科学院学报

Bronchial asthma is a common chronic respiratory disease,and its diagnosis is mainly based on symptoms,signs,and pulmonary function test.Wheezing is a major symptom of asthma attack,which shows no obvious sign in the early stage while appears after the disease has progressed.Therefore,bronchial asthma is difficult to be detected in early stages,which often leads to worsening of the disease conditions.Pulmonary function test can effectively monitor upper and lower airway abnormalities and is currently the main means for monitoring asthma.However,its accuracy is highly dependent on patient's motivation and cooperation,which obviously limits the scope of application,especially for preschoolers and infants.Hence,there is an urgent need for a new technology with the function of long-term breath sound monitoring and automatic breathing detection to overcome the existing clinical deficiencies.Breath sound analysis emerges in the era of medical artificial intelligence,which can digitally process and convert the collected respiratory sounds by using a variety of different methods to form characteristic signal parameters and model the relationship between parameters and diseases.As we know,breath sounds are closely related to airway changes,and thus the detection and analysis of the sounds can provide reliable clinical information for the progress and control evaluation of asthma.This review mainly summaries the research progress of respiratory sound analysis in recent years,hoping to provide reference for further research.

Clinical effect of feeding with calorie-enriched formula in children with ventricular septal defect and severe pneumonia / 中国当代儿科杂志

OBJECTIVE@#To study the effect of different energy feeding patterns on the nutritional status, clinical course, and outcome of children with congenital heart disease (CHD) and severe pneumonia.@*METHODS@#A total of 43 malnourished infants, aged 0.05). At discharge and 1 and 3 months after surgery, the control group had significantly higher degree of malnutrition and level of nutritional risk than the observation group (P<0.05). The analysis of variance with repeated measures showed significant differences in body weight, upper arm circumference, weight-for-age Z-score, height-for-age Z-score, weight-for-height Z-score, and albumin level at different time points and between different groups, and there was an interaction between group factors and time factors (P<0.05). Compared with the control group, the observation group had a significantly lower average daily intake of fluid, a significantly higher average daily intake of energy, and a significantly lower incidence rate of insufficient feeding during hospitalization (P<0.05). Compared with the control group, the observation group had significantly shorter length of hospital stay, duration of mechanical ventilation, and duration of postoperative pyrexia, as well as significantly lower hospital costs (P<0.05). No significant adverse reactions were observed in either group.@*CONCLUSIONS@#An appropriate increase in postoperative energy supply for children with CHD can improve the status of malnutrition and clinical outcome.

Relationship Study on Serum Levels of Procalcitonin and Pulmonary Function in Patients with Chronic Obstructive Pulmonary Disease / 现代检验医学杂志

Objective To study the relationship between the serum levels of procalcitonin (PCT) and pulmonary function in patients with chronic obstructive pulmonary disease (COPD).Methods From January 2016 to May 2107,88 cases of patients with COPD and 100 cases of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) were chosen as the object of study,pulmonary function was measured in all patients,grouped according to the standard of pulmonary function classification,and detected the serum levels of PCT by immunoturbidimetry.Results The serum levels of PCT were not statistically different among the COPD patients (F=1.401,P＞0.05).But among the AECOPD patients,the serum levels of PCT in the Ⅳ class of pulmonary function were significantly higher than that in the Ⅰ,Ⅱ class and Ⅲ class and this difference was statistically significant (F=9.128,P＜0.05).Conclusion The serum levels of PCT had significant reference value for the judgement of the severity of pulmonary function impairment in AECOPD patients.

Effects of volatile components in Oroxyli Semen on H22 bearing mice and its possible mechanisms / 中国药理学通报

Aim To study the inhibitory effect of volatile components in Oroxyli Semen on liver cancer and its possible mechanisms.Methods H22 bearing mouse model was used,the mice were divided into six groups:blank,model,positive (cytoxan,100 mg · kg-1),low-,mid-,and high-dose (17.5,35,and 70 mg · kg-1) volatile components groups,and then the mice were ig given once daily for consecutive 12 d.Then the tumor growth inhibitory rate,spleen and thymus indexes were calculated;the serum levels of IL-2,IL-6 were determined.HE staining was used to study of the apoptosis of the solid tumor.After treatment of SMMC-7721 cells with 0 ～ 1 g · L-1 of volatile components for 24,48 and 72 h,MTT assay was used to examine the proliferation.TUNEL method was applied to detect cell apoptosis,and RT-PCR method to detect Bax,Bcl-2,caspase-3 mRNA experssion.Results The inhibitory rate of volatile components high-dose on H22 bearing mice was 42.08％.The thymus index and the contents of serum IL-2 and IL-6 of H22 bearing mice were significantly higher than those in model group.Volatile components could significantly inhibit proliferation and induce apoptosis of SMMC-7721 cells,downregulate the expression of Bcl-2 mRNA,and up-regulate the expression of Bax,caspase-3 mRNA.Conclusions The volatile components in Oroxyli Semen have obvious anti-tumor activity in vitro and in vivo,and its mechanism may be related to enhancing immune system and promoting tumor cell apoptosis.

Analysis for comparative results of isotope dilution mass spectrometry in CDC-CRMLN project / 临床检验杂志

Objective To summarize and review the comparative results of the isotope dilution mass spectrometry in Cholesterol Reference Method Laboratory Network (CRMLN)project of the Centers for Disease Control and Prevention (CDC)of the United States in order to provide quality controls for determination of blood lipid.Methods The isotope dilution liquid chromatography tandem mass spectrometry (ID-LC/MS/MS)methods for determination of serum total cholesterol (TC)and triglycerides (TG)were developed to participate in the comparison of CRMLN.The survey was conducted every three months before 2016 and every half year from 2016.Four kinds of reference materials with two parallel tubes for each material and each tube in duplicate were determined in every survey.At least two certified reference materials used as quality control samples were analyzed simultaneously in each determination.Results In the 15 comparisons the CV of the TC determination method in our laboratory was 0.43％ while the CV of all the participated laboratories in CRMLN was 0.42％.The bias from the overall mean value in our laboratory was 0.22％ while the bias from the CDC target values was 0.58％.The CV of the TG determination method in 15 tests of our laboratory was 0.62％ and the bias was-0.98％ from the overall mean value and-0.80％ from the target values of CDC.Among the 60 results for comparison,98％ (59/60)of CV in the TC determination met with CDC requirement for precision (CV≤ 1％),and 70％ of bias (42/60) of the results met with CDC requirement for accuracy (bias ≤ 1％).For the 60 results in comparison of TG determination,92％ (55/60)of bias of the results met with the accuracy requirement of CDC (bias ≤2.55％).Conclusion In CRMLN comparison the results of TC and TG determined by ID-LC/MS/MS method were consistent with the values which were certified by CDC and determined by other network laboratories.The comparative surveys may play an important role in the standardization of lipid determination,and should be expected to provide experiences and technical supports in the comparative plan for reference measurement in our country.

Intravenous sedation with midazolam and propofol target controlled infusion on patients' perioperative anxiety under the mandibular third molar extraction / 北京大学学报(医学版)

Objective:To evaluate whether midazolam with propofol target controlled infusion (TCI intravenous sedation during the mandibular third molar extraction influences patients' perioperative anxiety.Methods:The subjects were patients who planned to undergo the mandibular third molar extraction in Peking University School and Hospital of Stomatology,whose state anxiety inventory (SAI) scores were ≥ 38 at the initial visit.They were divided into intravenous sedation group (IVS) and local anesthesia group (LA) on the basis of the planned intravenous sedation.Each group was divided into two subgroups according to the overall SAI scores at the initial visit:IVS-Ⅰ,LA-Ⅰ (SAI:38-50) and IVS-Ⅱ,LAⅡ (SAI:51-80).The anxiety before and after the surgery was evaluated by the SAI scores at the initial visit (T1),before surgery (T2) and 7 days after surgery (T3).The anxiety during the surgery was evaluated by the heart rate,blood pressure and visual analogue scale (VAS) scores.Results:There were no significant differences on SAI at T1,T2,and T3 in the two groups (P ＞ 0.05).The heart rate,blood pressure and VAS pain scores of IVS group were significantly lower than those of LA group during the surgery (P ＜ 0.001).Conclusion:Intravenous sedation with midazolam and propofol TCI was effective on the patients' anxiety during the third molar extraction,which successfully made the patients more comfortable and their heart rate,blood pressure and oxygen saturation more stable during the surgery.But there were no significant differences on the patients' anxiety at the initial visit (T1),before surgery (T2) and 7 days after surgery (T3) according to the SAI scores in the two groups.

Relationship between infants cow's milk protein allergy and gastroesophageal reflux disease / 中华实用儿科临床杂志

Objective To investigate the relationship between cow's milk protein allergy(CMPA)and gastroesophageal reflux disease(GERD)and the prognosis of GERD combined with CMPA.Methods Fifty patients(24 boys and 26 girls)with GERD were enrolled in this study from January 2015 to June 2016 at Department of Pediatrics,Tangdu Hospital of the Fourth Military Medical University.All children were treated with serum milk protein soluble IgE(sIgE)and milk protein avoidance test,and those with positive results of children's milk protein by provocation test and those with milk serum protein sIgE negative by milk protein provocation tests were diagnosed as CMPA children with GERD according to the CMPA diagnostic criteria and received diet therapy for 1 month and then their blood eosinophil ratio and 24-hour esophageal pH were monitored.Results Twenty-three cases(46％)of 50 children with GERD were diagnosed as CMPA.There was significant difference in clinical symptoms between GERD group and GERD combined with CMPA group(x2=22.78,P0.05).For children with GERD combined with CMPA,the patients received dietary treatment for 1 month.There was significant improvement in vomiting,runny nose/wheezing/cough and diarrhea(P0.05).The proportions of blood eosinophils were decreased after treatment compared with those before treatment [(2.7±1.8)％vs.(8.2±2.7)％,t=10.006,P<0.01].The results of 5 children's 24-hour esophageal pH monitoring showed that the reflux index and the number of acid GERD episodes were lower than before,and the difference was all statistically significant before and after(all P<0.05).Conclusions The occurrence of GERD in infants is partly related to CMPA,and the treatment of CMPA can relieve the clinical symptoms of GERD.

Advances in Chronic Pain Treatment / 现代生物医学进展

Chronic pain is a common clinical disease,which brings great burden to the patients.However,the pathogenesis underlying of chronic pain is complicated,which is affected by many factors,such as physiology,psychology and society.Therefore,the treatment of chronic pain has been a problem in clinical practice.Considering its complexity,a single way of treatment usually could not reach satisfactory results,so combination therapy is often used to treat chronic pain at present.The combination therapy includes pharmacological treatment,psychological approaches,interventional treatment,self management and so on.The treatment plans are distinct for different types of chronic pain,even the individual patients with the same kind of pain.The emergence of interdisciplinary rehabilitation programs shed light upon the treatment of chronic pain recent years.This paper reviewed the research on chronic pain treatment,in order to provide theoretical basis for clinical practice.

Effect of eicosapentaenoic acid on mRNA expression of tight junction protein ZO-1 in intestinal epithelial cells after Escherichia coli LF82 infection / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the change in the expression of tight junction protein ZO-1 in intestinal epithelial cells (Caco-2 cells) and the protective effect of eicosapentaenoic acid (EPA) after adherent-invasive Escherichia coli (E.coli) LF82 infection.</p><p><b>METHODS</b>The Caco-2 cell line was used to establish an in vitro model of tight junction of intestinal epithelial cells. Caco-2 cells were divided into EPA treatment groups (0, 25, 50, 100, and 200 μmol/L EPA) and EPA (0, 25, 50, 100, and 200 μmol/L EPA)+E.coli LF82 treatment (0, 6, and 12 hours) groups. A microscope was used to observe the morphological characteristics of the cells. MTT assay was used to determine the cell growth curve. The activity of alkaline phosphatase (ALP) at both sides of the cell membrane was compared to evaluate the Caco-2 cell model. MTT assay and flow cytometry were used to investigate the effects of different concentrations of EPA on the survival rate and apoptosis rate of Caco-2 cells. RT-qPCR was used to measure the mRNA expression of ZO-1 in Caco-2 cells after EPA and/or E.coli LF82 treatment. ELISA was used to measure the change in the level of tumor necrosis factor-α (TNF-α) in culture supernatant.</p><p><b>RESULTS</b>After EPA treatment (25 and 50 μmol/L), the proliferation of Caco-2 cells was induced in a dose-dependent manner. The survival rates of the cells were significantly higher than those in the control group (P<0.05). The EPA treatment (100 and 200 μmol/L) groups had a significant inhibitory effect on the proliferation of Caco-2 cells in a dose-dependent manner. The survival rates of the cells were significantly lower than those in the control group (P<0.05). The EPA treatment (100 and 200 μmol/L) groups had a significant increase in cell apoptosis rate compared with the control group (P<0.05). The 6- and 12-hour E.coli LF82 treatment groups had decreasing mRNA expression of ZO-1 in Caco-2 cells over the time of treatment and had significantly lower mRNA expression of ZO-1 than the untreated group (P<0.05). The Caco-2 cells treated with E.coli LF82 and 25 or 50 μmol/L EPA for 6 or 12 hours showed an increase in the mRNA expression of ZO-1 with the increasing concentration of EPA, as well as significantly higher mRNA expression of ZO-1 than the Caco-2 cells treated with E.coli LF82 alone (P<0.05). The Caco-2 cells treated with E.coli LF82 alone for 6 or 12 hours had increasing secretion of TNF-α over the time of treatment and had significantly higher secretion than the untreated Caco-2 cells (P<0.05). The Caco-2 cells treated with E.coli LF82 and 25 or 50 μmol/L EPA for 6 or 12 hours showed a reduction in the secretion of TNF-α with the increasing concentration of EPA and had significantly lower secretion than the Caco-2 cells treated with E.coli LF82 alone (P<0.05).</p><p><b>CONCLUSIONS</b>EPA can effectively prevent the destruction of tight junction of intestinal epithelial cells induced by E.coli LF82 infection and inhibit the secretion of inflammatory factors. Therefore, it has a certain protective effect on intestinal mucosal barrier.</p>

Prokinetics——now and in the future / 中华实用儿科临床杂志

Gastrointestinal motility disorders are in high incidence in children.Due to moderate prokinetic effects,poor symptomatic responses and the presence of adverse effects,there is a clear need for new classes of prokinetics.Currently available drug classes in adult include antidopami-nergic agents,serotonergic agents,and motilin-receptor while there are less available drug classes in children.The aim of the present article is to review and address the present use of promotility drugs in the treatment of different gastrointestinal motor disorders,as well as the potential for future developments.