Management of Rare Diseases in Children: Status Quo, Progress and Prospects / 罕见病研究

There is uniformed definition of rare diseases in children, which can be viewed as rare diseases that develop in childhood, or the childhood of patients with rare diseases. Rare diseases are rarely seen in clinical setting, various in types and difficult to diagnose and treat. In the past few years, with the rapid development of medical technology and the establishment and wide application of rare disease management systems, great progress has been made in the diagnosis and treatment of rare diseases. Although the management of rare diseases is being gradually expanded and enhanced, there are still challenges, or opportunities for further improvement. China is a vast country with imbalanced distribution of medical resources. In many places, people have limited knowledge about the pathogenesis of many rare diseases. Capacities vary in the detection, diagnosis, and treatment of rare disease in different places. As a result, most rare diseases are either misdiagnosed or not diagnosed at all. Therefore, it is of great significance to establish a hierarchical system for the management of rare diseases, i.e., appropriate triage, risk stratification, early diagnosis and scientific treatment, and integrate regional resources into rare disease management. Studies have confirmed the existance of heterogeneity of rare diseases, with more than half of them occurring at birth or in childhood and that they are associated with a high mortality rate and a high incidence of functional disabilities in survivors. Therefore, rare diseases in child-ren deserve more attention. Standardized, protocol-based, law-based management of rare diseases in children is in urgent need. The article aims to discuss the status quo of the management of rare diseases in children, to summarize the clinical progress of rare diseases in children and to explore its prospects in the future, in the hope to provide some reference for the management of rare diseases in children.

Application of PACS system in the standardized residency training of cardiovascular medicine / 中华医学教育探索杂志

Objective:To evaluate the effect of PACS system (picture archiving and communication system) in the standardized residency training of cardiovascular medicine.Methods:Fifty-nine residents taking the standardized residency training of cardiovascular medicine in Changhai Hospital from 2018 to 2019 were randomly divided into PACS teaching group ( n = 30) and traditional teaching group ( n = 29). The research group adopted the PACS system for the teaching of cardiovascular medicine, and the control group took the traditional teaching method. The teaching effect was evaluated by theoretical examination, imaging examination and questionnaire. SPSS 19.0 was used for t test and chi-square test. Results:The theoretical and film reading scores of the PACS teaching group were significantly higher than those of the control group [(87.70 ± 6.52) vs. (80.55 ± 8.63); (86.67 ± 6.33) vs. (77.48 ± 10.29), P < 0.05)]. The results of the questionnaire showed that PACS teaching method was helpful for residents to master cardiovascular knowledge, arouse their learning interest and improve their clinical thinking ability. The satisfaction with the teaching method in the PACS teaching group was significantly higher than that in the traditional teaching group [(9.22 ± 0.44) vs. (8.26 ± 0.72), P < 0.05]. Conclusion:The application of PACS system in the teaching of cardiovascular medicine can significantly improve the teaching effect of residents.

The association between sleep quality and the degree of coronary atherosclerotic stenosis / 中国医师杂志

Objective@#To explore the correlation between sleep and the severity of coronary artery stenosis, and to further guide the prevention and control of coronary heart disease.@*Methods@#A total of 302 patients, including 183 males and 119 females, were enrolled in the department of cardiology of Changhai hospital from February to June 2019. The patients were divided into three groups according to the degree of stenosis (atherosclerotic group, atherosclerotic group with degree of stenosis <50%, atherosclerotic group with degree of stenosis 50%-70%, and atherosclerotic group with degree of stenosis >70%). General information, comorbidities and Pittsburgh sleep quality index (PSQI) of patients in each group were analyzed to compare the differences and analyze the risk factors of aggravated coronary artery stenosis.@*Results@#There were statistically significant differences in age, gender and diabetes among all groups (P<0.05). There was no statistically significant difference in the incidence of hypertension and hyperlipidemia in each group (P>0.05). Spearman correlation analysis showed that PSQI score was positively correlated with the degree of atherosclerosis (P<0.01). In the multivariate regression model, poorer sleep quality (OR=1.75, 95% CI: 1.14-2.69, P<0.05), shorter sleep time (OR=1.64, 95% CI: 1.05-2.55, P<0.05) and more diurnal dysfunction (OR=1.45, 95% CI: 1.11-1.88, P<0.01) were correlated with increased coronary artery stenosis. Higher PSQI total score (OR=1.13, 95% CI: 1.06-1.20, P<0.01) and lower PSQI evaluation grade (very bad vs very good: 13.85, 95% CI: 1.56-122.82, P<0.05) were also related to the increase of coronary artery stenosis.@*Conclusions@#Poorer sleep quality, shorter sleep time and more diurnal dysfunction were independent risk factors for the aggravation of coronary artery stenosis. Higher Pittsburgh sleep quality index was significantly associated with the severity of coronary artery stenosis.

Analysis of drug resistance and risk factors of community-acquired urinary tract infection caused by extended-spectrum β-lactamase-producing Escherichia coli in children / 中华实用儿科临床杂志

Objective@#To investigate the drug resistance and risk factors of community-acquired urinary tract infection(UTI) caused by extended-spectrum β-lactamase(ESBLs)-producing Escherichia coli in children.@*Methods@#The clinical data of 125 children with community-acquired urinary tract infection caused by Escherichia coli were analyzed, who were hospitalized at Department of Pediatric Nephrology of Tianjin Children′s Hospital from June 2017 to June 2018.The ESBLs-producing group and the non ESBLs-producing group were named depending on the production of the ESBLs.WHONET 5.6 bacterial resistance monitoring software was used to calculate the drug resistance rate of bacteria.The drug resistance rate and clinical data were analyzed by adopting χ2 test and Fisher′s exact probability method, then, factors with statistical significance identified by single factor analysis were further analyzed by multivariate Logistic regression analysis.@*Results@#Among 125 strains of Escherichia coli, 68 strains(54.4%) were ESBLs-producing Escherichia coli and 57 strains(45.6%) were non ESBLs-producing.The drug resistance rates of ESBLs-producing Escherichia coli to penicillins, cephalosporins, quinolones and monocyclic beta-lactams were higher than those of non ESBLs-producing strains, and the drug resistance rates to Ampicillin, Piperacillin, Cefazolin, Cefuroxime, Ceftriaxone and Cefotaxime were nearly 100%.The resistance rates of ESBLs-producing strains to Imipenem, Meropenem, Amikacin, Furantoin, Cefotetan and Piperacillin/Tazobactam were lower (< 5%). Univariate analysis showed that there were significant differences in recurrent UTI (χ2=12.043, P<0.01) and use of third-generation cephalosporins in the past 3 months(χ2=28.545, P<0.01) between ESBLs-producing group and non ESBLs-producing group.Multivariate Logistic regression analysis showed that use of third-generation cephalosporins in the past 3 months was an independent risk factor of community-acquired UTI caused by ESBLs-producing Escherichia coli(OR=11.285, 95%CI: 3.140-39.134, Wald=13.972, P<0.01).@*Conclusions@#The isolation rate of ESBLs-producing Escherichia coli in children with community-acquired UTI is high, and the drug resistance rate is high, so children who used third-generation cephalosporins in the past 3 months were more likely to develop community-acquired UTI caused by ESBLs-producing Escherichia coli.

Clinical significance of detection of urine renal injury biomarkers in children with primary nephrotic syndrome / 中华实用儿科临床杂志

Objective@#To investigate the clinical significance of detection of urine renal injury biomarkers in children with primary nephrotic syndrome (PNS).@*Methods@#Seventy-nine children with PNS at the Department of Nephrology, Tianjin Children′s Hospital were enrolled from January to December 2016, who were given sufficient glucocorticoid for 4 weeks.According to the response to glucocorticoid, they were divided into steroid-sensitive nephrotic syndrome (SSNS) group (63 cases) and steroid-resistant nephrotic syndrome (SRNS) group (16 cases), then they were divided into simple type and nephritic type according to diagnostic criteria.Urinary levels of microalbuminuria (MAlb), transferrin (TfR), retinal binding protein (RBP), N-acetyl-β-D-glucosaminidase (NAG), α1-microglobulin (α1-MG) and β2-microglobulin (β2-MG) were measured in the children before and after treatment, and the data were analyzed by the statistical method.@*Results@#Before treatment, the levels of RBP, NAG, α1-MG and β2-MG in the SSNS group [0.91(1.80) mg/L, 28.00(31.5) U/L, 8.40(14.2) mg/L, 0.45(0.35) mg/L]were lower than those in SRNS group[3.94(4.82) mg/L, 37.10(18.20) U/L, 11.10(21.42) mg/L, 0.66(1.41) mg/L], and the differences were statistically significant (all P<0.05); After treatment, the MAlb, TfR, RBP, NAG, α1-MG, β2-MG in the SSNS group [14.10(5.60) mg/L, 0.40(1.60) mg/L, 0.26(0.38) mg/L, 7.90(9.10) U/L, 2.00(4.40) mg/L, 0.27(0.35) mg/L] were lower than those before treatment[MAlb: 1 704.00(1 995.60) mg/L, TfR: 142.10(81.90) mg/L] and those after treatment in the SRNS group[557.90(1 857.17) mg/L, 117.40(102.10) mg/L, 4.19(5.15) mg/L, 38.80(32.43) U/L, 10.85(16.60) mg/L, 0.63(0.91) mg/L], and the differences were statistically significant (all P<0.05). However, before and after treatment, except for MAlb[before treatment: 2 258.75(2 028.43) mg/L], the indicators in the SRNS group were not significantly improved.Before treatment, the RBP in the SRNS group was significantly higher than that in the SSNS group in children with simple type PNS, and the RBP, NAG, α1-MG and β2-MG in the SRNS group were significantly higher than those in the SSNS group in children with nephritic type PNS (all P<0.05). According to receiver operating characteristic curve, there were obvious differences in the urinary levels of RBP, NAG and β2-MG, and area under curve(AUC) was 0.858, 0.837 and 0.679, respectively, all of which were <0.9, so the value of diagnosis was not high.Logistic regression analysis was used to identify RBP and NAG as influencing factors and to establish a model.Through the combined detection of these two indicators, the diagnostic value was higher (AUC was 0.956), and when the diagnostic sensitivity was 93.8%, the specificity could reach 82.5%.@*Conclusions@#Urinary RBP, NAG, α1-MG and β2-MG can early reflect tubular interstitial impairment in children with PNS, especially SRNS.Combined detection of RBP and NAG has certain value in predicting the efficacy of glucocorticoid.

The association between sleep quality and the degree of coronary atherosclerotic stenosis / 中国医师杂志

Objective To explore the correlation between sleep and the severity of coronary artery stenosis,and to further guide the prevention and control of coronary heart disease.Methods A total of 302 patients,including 183 males and 119 females,were enrolled in the department of cardiology of Changhai hospital from February to June 2019.The patients were divided into three groups according to the degree of stenosis (atherosclerotic group,atherosclerotic group with degree of stenosis ＜ 50％,atherosclerotic group with degree of stenosis 50％-70％,and atherosclerotic group with degree of stenosis ＞ 70％).General information,comorbidities and Pittsburgh sleep quality index (PSQI) of patients in each group were analyzed to compare the differences and analyze the risk factors of aggravated coronary artery stenosis.Results There were statistically significant differences in age,gender and diabetes among all groups (P ＜ 0.05).There was no statistically significant difference in the incidence of hypertension and hyperlipidemia in each group (P ＞ 0.05).Spearman correlation analysis showed that PSQI score was positively correlated with the degree of atherosclerosis (P ＜ 0.01).In the multivariate regression model,poorer sleep quality (OR =1.75,95％ CI:1.14-2.69,P ＜0.05),shorter sleep time (OR =1.64,95％ CI:1.05-2.55,P ＜0.05) and more diurnal dysfunction (OR =1.45,95％ CI:1.11-1.88,P ＜0.01) were correlated with increased coronary artery stenosis.Higher PSQI total score (OR =1.13,95％ CI:1.06-1.20,P ＜ 0.01)and lower PSQI evaluation grade (very bad vs very good:13.85,95％ CI:1.56-122.82,P＜0.05) were also related to the increase of coronary artery stenosis.Conclusions Poorer sleep quality,shorter sleep time and more diurnal dysfunction were independent risk factors for the aggravation of coronary artery stenosis.Higher Pittsburgh sleep quality index was significantly associated with the severity of coronary artery ste-nosis.

A multicenter study of reference intervals for 15 laboratory parameters in Chinese children / 中华儿科杂志

Objective@#To establish comprehensive laboratory reference intervals for Chinese children.@*Methods@#This was a cross-sectional multicenter study. From June 2013 to December 2014, eligible healthy children aged from 6-month to 17-year were enrolled from 20 medical centers with informed consent. They were assessed by physical examination, questionnaire survey and abdominal ultrasound for eligibility. Fasting blood samples were collected and delivered to central laboratory. Measurements of 15 clinical laboratory parameters were performed, including estradiol (E2), testosterone(T), luteinizing hormone(LH), follicle-stimulating hormone(FSH), alanine transaminase(ALT), serum creatinine(Scr), cystatin C, immunoglobulin A(IgA), immunoglobulin G(IgG), immunoglobulin M(IgM), complement (C3, C4), alkaline phosphatase(ALP), uric acid(UA) and creatine kinase(CK). Reference intervals were established according to central 95% confidence intervals for reference population, stratified by age and sex.@*Results@#In total, 2 259 children were enrolled. Finally, 1 648 children were eligible for this study, including 830 boys and 818 girls, at a mean age of 7.4 years. Age- and sex- specific reference intervals have been established for the parameters. Reference intervals of sex hormones increased gradually with age. Concentrations of ALT, cystatin C, ALP and CK were higher in children under 2 years old. Serum levels of sex hormones, creatinine, immunoglobin, CK, ALP and urea increased rapidly in adolescence, with significant sex difference. In addition, reference intervals were variable depending on assay methods. Concentrations of ALT detected by reagents with pyridoxal 5'-phosphate(PLP) were higher than those detected by reagents without PLP. Compared with enzymatic method, Jaffe assay always got higher results of serum creatinine, especially in children younger than 9 years old.@*Conclusion@#This study established age- and sex- specific reference intervals, for 15 clinical laboratory parameters based on defined healthy children.

Risk factor and drug-resistance analysis of acute pyelonephritis in children / 中华实用儿科临床杂志

Objective To investigate the distribution and antibiotic resistance to pathogens isolated from children with acute pyelonephritis(APN) and explore the risk factors for it.Methods A retrospective analysis was performed on the distribution and antibiotic resistance to 173 pathogens isolated from 264 children with APN who hospitalized at Tianjin Children's Hospital from March 2012 to March 2017.The antibiotic resistance to pathogens was determined by using antimicrobial susceptibility.The clinical indicators of children were compared with APN and 200 children with lower urinary tract infection,including sex,age,index of blood and urine.The risk factors for APN were analyzed.Results Gram-negative bacilli were the main pathogen (61.3％),and involved Escherichia coil (E.coil) of 34.1％.Gram-positive cocci accounted for 38.7％,and involved enterococcus faecium of 24.3％.The resistance rate of E.coli to Ampicillin was the highest(89.8％),but the rate significantly decreased by adding Amoxicillin/Clavulanic acid(47.5％).Compared with Ampicillin,the difference was statistically significant(P ＜ 0.05).The resistance rate of E.coli to Tocefoperazone/Sulbactam was significantly lower than to other cephalosporins(P ＜ 0.01).E.coli had lowest resistance rate to Imipenem (0.03 ％).The resistance rate of enterococcus faecium was low to Linezolid and Vancomycin(＜ 5％).Single and multiple regression analysis revealed that younger than 1 year old,children with urinary tract malformation,increasing procalcitonin (PCT) of blood and β2-microglobulin (β2-MG) and neutrophil gelatinase-associated lipocalin (NGAL) of urine were all the risk factors of APN (all P ＜ 0.05).Conclusions E.coil is the major pathogen in children with APN and the enterococci-caused APN has been increasing.These pathogens have a high antibiotic resistance rate.Antimicrobial therapy should be based on the findings of urine culture and antimicrobial susceptibility test.In the children,less than 1 year old,with urinary tract malformation,the increasing PCT of blood,β2-MG and NGAL of urine are the risk factors for APN.

Correlation of soluble thrombomodulin and high sensitive C reactive protein with hypercoagulability in children with primary nephrotic syndrome / 中华实用儿科临床杂志

Objective To explore the correlations of soluble thrombomodulin (sTM) and high sensitive C reactive protein(hs-CRP) levels with the hypercoagulable state and indicators of predicting thrombosis in children with primary nephrotic syndrome(PNS).Methods Sixty-four PNS patients who had primary clinical diagnosis or recurrence after hormone withdrawal for 6 months or more hospitalized in Department of Urology,the Second Children's Hospital of Tianjin from January 2010 to January 2014 were selected as PNS group.Thirty patients with inguinal hernia undergoing elective surgery hospitalized in Department of Surgery,the Second Children's Hospital of Tianjin from January 2010 to January 2014 were selected as control group.All the selected patients were extracted for venous blood samples,and the double-antibody sandwich enzyme-linked immunosorbent assay was used to detect plasma sTM levels,while immunoturbidimetric assay was used to detect plasma hs-CRP levels;the indicators of predicting thrombosis as blood lipid and fibrinogen(Fb) etc.were simultaneously detected.Inspection results were compared and the correlation was analyzed by using statistical methods.Results The level of plasma sTM in children with PNS was significantly higher than that in the control group[(1.63 ±0.68) μg/L vs.(0.30 ±0.24) μg/L],and the difference was statistically significant between the 2 groups (t =12.545,P ＜ 0.05).The level of plasma sTM in PNS group with urine protein negative was significantly lower than that before hormone treatment[(1.05 ± 0.56) μg/L vs.(1.63 ± 0.68) μg/L],and there was a statistically significant difference(t =6.298,P ＜ 0.05).The level of plasma sTM in children with PNS had positive correlation with 24 h urinary protein,low density lipoprotein,apolipoprotein B,lipoprotein a and Fb (r =0.379,0.203,0.184,0.177,0.224,all P ＜ 0.05).The level of plasma hs-CRP in children with PNS was significantly higher than that in the control group [(1.9 ± 1.7) mg/L vs.(0.7 ± 0.6) mg/L],and the difference was statistically significant between the 2 groups (t =3.487,P ＜ 0.05).In PNS group,the level of plasma hs-CRP with urine protein negative was significandy lower than that before hormone treatment[(0.4 ±0.3) mg/L vs.(1.9 ± 1.7) mg/L],and there was a statistically significant difference (t =5.473,P ＜ 0.05).The level of plasma hs-CRP in children with PNS was negatively correlated with plasma albumin (r =-0.194,P ＜ 0.05),but positively correlated with Fb (r =0.257,P ＜ 0.01).Plasma sTM and hs-CRP levels in children with PNS were positively correlated (r =0.395,P ＜ 0.05).Conclusions sTM involves in the formation process of PNS hypercoagulable state possibly through dual influencing by blood coagulation process and blood lipids.sTM may be used as one of the reference indicators for PNS activity and prediction of thrombosis.Plasma hs-CRP reflects the micro-inflammatory state in children with PNS,and involves in the formation of hypercoagulability by effecting blood coagulation process,and should be used as indicators for monitoring the hypercoagulability of active PNS.

The effects of ACTH and Huaiqihuang on the treatment of recurrence nephrotic syndrome in children / 天津医药

Objective To observe the effects and safety of adrenocorticotropic hormone (ACTH) combined with Huaiqihuang on frequent relapse nephrotic syndrome (FRNS) in children. Methods Fifty-five child patients with FRNS were divided into control group, which was given glucocorticoid (GC) to maintain the treatment (group A, n=10), Huaiqihuang group (group B, n=17), ACTH group (group C, n=14) and ACTH combined with Huaiqihuang group (combined treatment group, group D, n=14). Continuous treatment was for 12 months. The GC treatment doses, the levels of basal secretion of adrenal cortex and adrenal cortex reserve were recorded at 6-month and 12-month respectively. And the recurrence rate and adverse reactions were observed in four groups. Results After 6-month treatment, the doses of GC were significantly lower in group C and group D than those in group A and group B (P0.05). After treatment for 6 months and 12 months, the recurrence rates of nephrotic syndrome were significantly lower in group C and group D than those of group A and group B (P<0.05). Conclusion The simple application of ACTH and the combination of Huaiqihuang can relieve the inhibition of long-term using GC on hypothalamic pituitary adrenal axis in FRNS patients.

Effects of ACTH combined with Huaiqihuang on rat hypothalamic pituitary adrenal axis / 天津医药

Objective To investigate the effects of adrenocorticotropic hormone (ACTH)combined with Huaiqihuang on hypothalamic pituitary adrenal (HPA) in rats. Methods Fifty rats were randomly divided into five groups according to the random number table method:normal control group (group A), prednisone group (group B), Huaiqihuang group (group C), ACTH group (group D) and combined treatment group (group E) with 10 rats in each group. Rats in group B, C, D and E were gavaged by acetic acid prednisone water solution 12.5 mg/(kg · d) for 4 weeks to establish HPA axis suppression model. Group A was given distilled water 10 mL/(kg·d) as control. Rats in group C and E were gavaged with Huaiqihuang 5 g/(kg·d) 30 minutes after intragastric administration of prednisone acetate. At the third week of the experiment, group D and E were subcutaneous injected with ACTH 200 μg/(kg·d). The serum cortisol levels were measured respectively at the start of the ex?periment, 2 weeks and 4 weeks of experiment. Animals were sacrificed at the end of the experiment, and then weights of the pituitary, adrenal glands and the viscera index were calculated. The pathological changes of the pituitary and adrenal glands were observed by HE stainning. Results After 2 weeks, the serum cortisol levels were significantly lower in group B, C, D and E than those of group A (Pgroup D>group C (P<0.05). At the same time, the weights of pituitary and adrenal gland and the viscera in?dex were higher in the three groups than those of B group (P<0.05). The HE staining showed that there were no significant changes in the distal part of the pituitary gland in five groups. The adrenal cortex zona was thinning and the structure was dis?ordered in group B. There were different degrees of hyperplasia in group C, group D, and group E, which was the most obvi?ous in group E. Conclusion ACTH combined with Huaiqihuang can promote adrenal cortex zona hyperplasia and cortisol secretion, which reduces the glucocorticoid induced inhibition of HPA axis in rats.

Effect of Azithromycin on the level of interleukin - 23,interleukin - 17 in serum of rats with Adriamycin -induced nephrosis / 中华实用儿科临床杂志

Objective To explore the effect of Azithromycin on the immune mechanisms through the IL - 23 /IL - 17 axis way by observing the changes in serum levels of IL - 23,IL - 17 in rats with Adriamycin - induced nephro-sis. Methods A total of 135 rats were randomly divided into control group,model group,Azithromycin intervention group,Prednisone intervention group and united intervention group. The model was induced through a tail intravenous injection of Adriamycin for 2 times. Nine rats were randomly selected from every group to detect blood and urinary bio-chemistry,and to observe the changes of the serum levels of IL - 23,IL - 17 by enzyme - linked immunosorbent assay in 4,6,and 8 weeks. Results Compared with the model group in the 8th week,the levels of 24 - hour urinary protein [model group(354. 83 ± 70. 87)mg/ d,Azithromycin intervention group(94. 59 ± 22. 67)mg/ d,Prenisone intervention group(65. 64 ± 8. 71)mg/ d,united intervention group(47. 44 ± 9. 56)mg/ d],cholesterol[ model group(8. 71 ± 1. 60)mmol/ L,Azithromycin intervention group(3. 54 ± 0. 30)mmol/ L,Prenisone intervention group(3. 10 ± 0. 18) mmol/ L,united intervention group(2. 56 ± 0. 40)mmol/ L]were reduced significantly,while the levels of albumin [model group(16. 77 ± 3. 15)g/ L,Azithromycin intervention group(33. 82 ± 1. 16)g/ L,Prenisone intervention group (37. 80 ± 2. 73)g/ L,united intervention group(40. 78 ± 2. 63)g/ L]were increased obviously in the intervention groups,and the differences were statistically significant(F = 152. 243,99. 838,155. 836,all P ﹤ 0. 05). The serum levels of IL - 23[model group(29. 60 ± 3. 97)ng/ L,Azithromycin intervention group(29. 61 ± 2. 62)ng/ L,Prenisone intervention group(29. 74 ± 2. 23)ng/ L,united intervention group(30. 31 ± 2. 20)ng/ L],IL - 17[ model group (22. 38 ± 2. 51)ng/ L,Azithromycin intervention group(21. 97 ± 1. 89)ng/ L,Prenisone intervention group(21. 43 ± 2. 42)ng/ L,united intervention group(21. 51 ± 2. 07)ng/ L]in the model group and 3 intervention groups were higher than the control group[(17. 35 ± 3. 01)ng/ L,(14. 03 ± 2. 42)ng/ L]in the 4th week,and there were significant differences(F = 33. 819,21. 373,all P ﹤ 0. 05);and the levels of IL - 23[in the 6th week,Azithromycin intervention group(27. 20 ± 1. 71)ng/ L,Prenisone intervention group(24. 39 ± 2. 06)ng/ L,united intervention group(21. 41 ± 1. 71)ng/ L,model group(35. 78 ± 3. 21)ng/ L;in the 8th week,Azithromycin intervention group(24. 60 ± 2. 91) ng/ L,Prenisone intervention group(21. 01 ± 1. 02)ng/ L,united intervention group(18. 93 ± 1. 35)ng/ L,model group (44. 47 ± 7. 84)ng/ L],IL - 17[in the 6th week,Azithromycin intervention group(19. 12 ± 0. 37)ng/ L,Prenidone in-tervention group(18. 54 ± 0. 36)ng/ L,united intervention group(17. 57 ± 0. 42)ng/ L,model group(26. 69 ± 3. 70) ng/ L;in the 8th week,Azithromycin intervention group(17. 44 ± 0. 46)ng/ L,Prenidone intervention group(16. 37 ± 0. 49)ng/ L,united intervention group(14. 71 ± 0. 99)ng/ L,model group(34. 03 ± 3. 45)ng/ L]in the 3 intervention groups were significantly lower than those of the model group in the 6th ,8th week(F = 82. 963,44. 659 in the 6th week, F = 75. 085,200. 383 in the 8th week,all P ﹤ 0. 05). The levels of IL - 23,IL - 17 in united intervention group were lower than those in respective intervention groups(P ﹤ 0. 05),and the levels in Prednisone intervention group were lower than those in Azithromycin intervention group(P ﹤ 0. 05). Conclusions IL - 23 / IL - 17 axis' high activity may be one of the immunologic mechanisms of Adriamycin - induced nephrosis. Azithromycin may inhibit the high activity of IL - 23 / IL - 17 axis to relieve the Adriamycin - induced nephrosis. The inhibition on IL - 23 / IL - 17 axis of Azithro-mycin was similar to Prednisone,and Azithromycin may enhance the effectiveness of Prednisone.

Research advances of membranoproliferative glomerulonephritis in children / 国际儿科学杂志

Membranoproliferative glomerulonephritis(MPGN)is immune pathological diagnosis,and it has all sorts of clinical manifestations,poor prognosis and high case fatality rate.The latest classification of MPGN is divided into immunecomplex-mediated and complement-mediated.On the basis of the potential patho-physiology,its related causes can be assessed in order to choose a more appropriate treatment method.Long alter-nate day glucocorticoid-therapy is beneficial to idiopathic MPGN in children.Biological agents used in the treat-ment of MPGN has made great progresses.

Application of gene chip in nephritic syndrome research / 天津医药

Nephrotic syndrome is a common kidney disease in childhood. Its pathogenesis has not been fully elucidat?ed. In recent years, gene chip is maturing and widely used in many fields. Its application in nephrotic syndrome could pro?vide important information of its pathogenesis and treatment target at gene level. This article reveiwed the current application of the gene chip technology and its prospects in the nephrotic syndrome.

Clinical significance of determination of the expression levels of TGF-β1 and IL-18 mRNA in children with primary nephrotic syndrome / 临床儿科杂志

Objective To study the clinical significance of transforming growth factor (TGF)-β1 and interleukin (IL)-18 mRNA in the diagnosis and evaluation of disease severity of primary nephrotic syndrome (PNS) in children. Methods The ex-pression levels of TGF-β1 and IL-18 mRNA in peripheral blood mononuclear cells (PBMC) were measured by real-time lfuorescent quantitative polymerase reaction (RT-PCR) in 77 children with PNS and 30 healthy children (control group). Results In children with steroid-sensitive nephrotic syndrome (SSNS), the expression levels of TGF-β1 and IL-18 mRNA before treatment and at 1, 4 weeks after hormone therapy were signiifcantly lower in children with simple type nephrotic syndrome than those in children with nephritic type nephrotic syndrome (P<0.05). The level of TGF-β1 mRNA before treatment was signiifcantly lower in children with SSNS than that in children with steroid-resistant nephrotic syndrome (SRNS). With the extension of hormone therapy, the expression levels of TGF-β1 mRNA showed a trend of declining in children with PNA. In children with SRNS, the expression levels of TGF-β1 and IL-18 mRNA before treatment and at 1, 4 weeks after hormone therapy were signiifcantly lower in children with simple type NS than those in children with nephritic type nephrotic syndrome (P<0.05). In children with SSNS, the levels of TGF-β1 and IL-18 mRNA were signiifcantly higher in acute phase than those in the remission phase. Conclusions At the early stage of PNS, the detection of the expression levels of TGF-β1 and IL-18 mRNA is useful for evaluatation of disease activity, clinical identiifcation of nephritic type nephrotic syndrome and simple type nephrotic syndrome and early prediction of SRNS.

Application of TBL model in common diseases teaching for pre-selected medical non-commis-sioned officer trainees / 中华医学教育探索杂志

Objective To explore the comparative advantage of Team based learning (TBL) in common diseases teaching among pre-selected trainees for medical non-commissioned officer. Methods 200 trainees were randomly divided into two groups of equal size (each having 100 trainees), one TBL group and another lecture based learning (LBL) group as the control group. The teaching content was both Chapters of High Altitude Illness and Hypertension. In the LBL control group, the traditional lec-ture based teaching and learning manner was followed. In contrast, the trainees in the TBL group were assigned pre-lecture self-learning outline and questions to discuss in advance, team-based group dis-cussion was conducted, and scene simulation with typical disease case analysis were adopted in class. In both groups, the teaching effectiveness were evaluated by both exam test and questionnaire manner. Results It turned out the team based learning model resulted in significantly improved overall trainee assessment scores (88.90 ± 5.28 vs. 76.10 ± 5.12, P<0.05) and higher overall teacher satisfaction scores (8.63 ± 0.85 vs 7.18 ± 0.72, P<0.05), compared to the LBL group. Conclusion TBL model is more effective in improving trainees' capabilities of cultivating team work spirit, self-confidence, learn-ing enthusiasm, problem analysis and knowledge application. TBL model significantly brings more advantage in teaching pre-selected trainees for medical non-commissioned officer.

Clinical study on combined urine biomarker detection in kidney injury of child CMV infection / 天津医药

Objective To explore changes of urine transferrin (TFR),micro albumin (mALb),β2 microspheres protein (MG),α1MG and N-acetylβ-D amino group (NAG) in children with kidney injury induced by cytomegalovirus (CMV) infec?tion, and the outcome after treatment. Methods Fifty children with CMV infection were used as case group, and 35 chil?dren of convalescence stage of upper respiratory tract infection were used as control group. The serum levels of creatinine (Scr), blood urea nitrogen (BUN),β2MG, liver function, CMV-IgM, CMV-PCR and brainstem auditory (BAEP), head CT and urine routine test, urine TFR, mALb,β2MG,α2MG and NAG were detected. The sputum CMV-PCR was detected if childrencombined with CMV pneumonia. Ganciclovir (5mg/kg) was given to two groups, 1/12 h i.v. for 14 d. The urine TFR,mALb,β2MG, α2MG and NAG were detected again after treatment. Results There were no significant differences in the urine mALb and TFR between the two groups. The urine levels ofα1MG, NAG andβ2MG were higher in case group than those of control group. The urine levels ofα1MG, NAG andβ2MG were decreased after 2-week treatment in case group. There were no significant differences in urine mALb and TFR before and after treatment. Conclusion The combined detection ofβ2MG,α1MG and NAG can predict CMV kidney damage in children at a early stage.

Intervention effect of leukotriene receptor antagonist on adriamycin-induced nephropathy rats / 中华实用儿科临床杂志

Objective To explore the effect of leukotriene receptor antagonist (LTRAs,montelukast) on serum indicators,urine indicators,renal pathology,intercellular adhesion molecule-1 (ICAM-1),nephrin and podocalyxin on renal tissue in adriamycin(ADR)-induced nephropathy(ADN) rats.Methods ADN was induced through a tail intravenons injection of ADR.The 40 healthy male Wistar rats were randomly divided into 5 groups:group A (control group),group B(ADN group),group C(prednisone-treated group),group D(montelukast-treated group) and group E (prednisone and montelukast-treated group).Twenty-four-hour urinary protein (24 h-up) and serum index were measured serially in the 4th,8th week and the values of creatinine clearance rate(Ccr) were calculated.At the end of the 8th week,all rats were sacrificed to collect kidney tissues for microscopy observation of renal pathological changes.The expression of nephrin,podocalyxin and ICAM-1 in renal tissues were detected through immunohistochemistry method.Results Compared with group A,in the 4th week,24 h-up and albumin reached the level of ADR nephropathy model.Compared with group B,in the 8th week,24 h-up,cholesterol,serum creatinine and renal pathology changes in the 3 treated groups were significantly reduced (P ＜ 0.05),but serum total protein,albumin and Ccr significantly increased (P ＜ 0.05),while extracellular matrix/glomerulararea and renal pathology score significantly reduced (P ＜ 0.01),and ICAM-1 significantly decreased(P ＜0.01).Compared with group C and group D,expressions of nephrin and podocalyxin in group E were the highest.Besides,the curative effect of integrated treatment was better than other treatments.Conclusions Maybe through inhibition of ICAM-1,LTRAs had a protective effect on renal tissue.The integrated treatment of LTRAs with prednisone has a synergistic effect and drug effect is superior to any drug alone in ADN.

Analysis of frequent relapses related factors of primary nephrotic syndrome in children / 国际儿科学杂志

Objective To explore the influencing factors of frequent relapse primary nephritic syndrome (PNS) in children according to the statistical analysis of their clinical data and laboratory examinations. Method We collected in-hospital and out-patient medical records of children who were diagnosed PNS from Jan. 2007 to Feb. 2010 and whole clinical data were analyzed. Results In 245 cases of children with steroid sensitine nephrotic syndrome, non-frequent replapse (NFR) accounted for 82.4% and frequent relapse (FR) accounted for 17.6%. In univariate analysis, period of first relapse between initial treatment remission within 3 months , level of serum total protein and cholesterol and IgE at onset had statistical significance in FR children and NFR children, which were significant predictors of FR. The logistic regression analysis revealed that the first relapse after initial treatment remission within 3 months and increasing of serum IgE level (more than 358 IU/ml)were risk factors of FR. Among frequent relapses factors, infection, especially upper respiratory tract infection was the first (65. 1%). The relapse with motivation mainly in January to March, accounted for 30. 4%. Conclusion FR had a proportion of 17. 6% in children with PNS under regular glucocorticoid treatment. It showed seasonality feature that relapse. peak in winter and spring. Level of the serum total protein less than 40g/L and cholesterol more than 10mmol/L at onset can be predictive index of FR. Infections are the main motivation of relapse, but the relapse by irregular treatment and specific constitutions should be pay more attentions too.

Intervention of azithromycin on adriamycin-induced nephropathy rats / 中华肾脏病杂志

Objective To investigate the effects of azithromycin on serum indicators, urine indicators, renal pathology, intercellular adhesion molecule-1 (ICAM-1), nephrin and podocalyxin in adriamycin(ADR)-induced nephropathy(ADN) rats. Methods ADR nephropathy was induced by a tail intravenous injection of ADR. The rats were randomly divided into azithromycin-treated group, prednisone -treated group, integrated treatment group, model group and control group. Serum index and 24 h urine protein were measured serially at 0, 4th, 8th weeks. The values of creatinine clearance (Ccr) were calculated. Kidney tissues were collected for microscopy observation. The expressions of nephrin, podocalyxin and ICAM-1 in renal tissue were detected by immunohistochemistry SP. Results Compared with normal control group, at the 4th week, 24 hours urine protein and albumin reached the level of ADR nephropathy model. Compared with model group, at the 8th week, 24 h urine protein, cholesterol, serum creatinine, renal pathology changes in the three treated group rats were significantly reduced (P<0.05), serum total protein, albumin and Ccr (except C group) significantly raised (P<0.05), ECM/GA and renal pathology score significantly reduced (P<0.01), ICAM-1 significantly decreased (P<0.01), nephrin and podocalyxin significantly increased. Besides, the curative effect of integrated treatment was better than other treatment group. Conclusions Azithromycin induces similar responses in ADR nephropathy as prednisone, but its early protective effect of renal function is worse than prednisone.The integrated treatment of azithromycin and prednisone has a synergistic effect, and the efficacy is superior to each drug alone.