Objective To explore the phenotype-genotype correlation of X-linked agammaglobulinemia（XLA） between clinical and immunological phenotypes and gene cDNA mutaions.
Methods Using anti-BTK monoclone antibody the expression level of BTK protein was measured by flowcytometry. The BTK mutations in XLA patients were detected using PCR and direct sequencing. Some of the patients′ mother and relatives were also taken BTK mutation analysis.
Results ①Forty of 50 XLA patients were identified to have BTK gene mutation.The major types of BTK mutation were missense(16 cases) and nonsense mutations(13 cases).②The age of onset of the XLA patients with missense mutations and other mutation were (1.4±1.1) and （1.4±0.7）years（P=0.45). The proportion of missense mutation increased, whereas the proportion of nonsense mutation decreased with the age of onset increasing. ③The numbers of circulating B cells of 34 cases(85%) were below 0.1%; 4 cases were between 1% and 2%. Among these 4 patients, two cases were missense mutation, one case was nonsense mutation and one case was splice-site mutation. Two cases with 2% B cells carried all missense mutiation. ④The major types of BTK mutation of the patients with low levels of serum IgG(<3 g·L-1) were missense mutation and nonsense mutation. ⑤There was no significant difference in exppression level of BTK protein between the patients with missense mutation and patients with other mutation types. ⑥6 of 21 cases with 2031 polymorphism had severe arthritis.Among 19 cases without 2031 polymorphism,3 cases had recurrent arthritis. ⑦28 of 32 mothers (87.5%) were confirmed to be carriers of BTK mutation.
Conclusions There was no clear genotype-phenotype correlation in Chinese XLA patients. Missense and nonsense mtation were the most common types of mutation in Chinese XLA patients. Missense mutation may be related to relatively high levels of IgG and expression level of BTK protein. Polymorphic variant (2031T>C) in exon 18 may partly contribute to the clinical phenotype of arthritis.
Objective The purpose of this cross-sectional study was to examine the prevalence of behavior problems and associated protective and risk factors among children aged 3 to 6 years in Huangpu district of Guangzhou.
Methods A community-based sample of 1 170 children was assessed with the Strengths and Difficulties Questionnaire(SDQ), Behavioral Style Questionnaire(BSQ), Family Environment Scale(FES) and a self-administered questionnaire including demographic characteristicts and children′s pre-,peri- and postnatal condition.
Results Totally 11.4%(134/1 170) children were rated as abnormal without significant gender differences. The most prevalent behavior problem was peer problem(23.2%), followed by hyperactivity(16.6%),conduct(11.8%),emotion(8.4%) and prosocial(8.4%). Multiple linear regression models explained 50% of the total variance of SDQ total difficulties score for children.Paternal educational,cohesion and intellectual-cultural orientation of family environment were significant protective factors against behaviour problems. Joint family,child′s medical history(congenital diseases,brain injury),temperamental low persistence, low adaptability, negative emotionality,low rhythmicity,high intensity and high activity were associated with higher SDQ total difficulties score (P<0.05).
Conclusions This study is consistent with previously reported risk factors for child behavior problems, and supports the need for a focus on early intervention and prevention strategies in the child mental health field.
Objective To analyze the clinical epidemiological characteristics of pediatric tuberculosis (TB) patients.
Methods A retrospective, descriptive study was undertaken among pediatric TB patients admitted to Beijing Children′s Hospital from January 2002 to December 2010. Clinical data including age, manifestation, type of TB and treatment were collected. Patients were classified into 3 group based on their history of BBC vaccination. Logistic regression analysis was applied to analyze the risk factors to the efficacy of TB treatment.
Results ① Overall, 1 212 hospitalized TB children were enrolled. Distribution of types of TB in 9 years was similar. Main types of TB were pulmonary TB (45.5%, 552/1 212), extra-pulmonary TB (23.5%, 285/1 212 and hematogenous disseminated pulmonary TB(15.8%, 191/1 212). 57.2%(163/285) extra-pulmonary TB was mainly meningitis. ② The age of onset for all forms of TB showed a bimodal distribution, under 4 years old and 7-12 years old, accounting for 42.0% (509/1 212) and 30.5% (370/1 212) of the total cases respectively. Severe TB ( hematogenous disseminated pulmonary TB or tubercular meningitis) were mainly observed in infants, and the proportion gradually decreased with increasing age. ③ The proportion of severe TB in BCG-vaccinated patients was lower than that in non-vaccinated patients, 26.9% and 34.6% respectively(P=0.004). ④ TB treatment rate of success was related to sex and types of TB in children. Treatment rate of success was lower in females (77.8%) than in males (83.8%), P=0.015. Treatment rate of success was the highest in patients with Pulmonary TB (84.2%) and was the lowest in patients with hematogenous disseminated pulmonary TB (73.8%), P=0.006.
Conclusions Pediatric TB was mainly observed in children under 4 years old. Compared with adults TB, children were more susceptible to extra-pulmonary TB and severe TB. Treatment outcome of pediatric TB was poor in severe TB patients and in females. BCG was effective in preventing severe TB especially in infants. BCG vaccination should be strengthened in order to prevent the occurrence of TB in young age children, especially the occurrence of severe TB.
Objective To investigate the prevalence of common respiratory viruses in infants and young children with acute respiratory infection (ARI) during the pandemic of 2009 influenza A(H1N1) in Beijing．
Methods Primers and probes were designed to develop a novel multiplex real-time PCR for the detection of 7 respiratory viruses including respiratory syncytial virus (RSV) types A and B, parainfluenza virus (PIV) types 1, 2 and 3, adenovirus (ADV) and human bocavirus(HBoV) in clinical samples. Clinical specimens were collected from children who visited the Children′s Hospital affiliated to Capital Institute of Pediatrics with ARI from June 2009 to February 2010 and had been tested negative for 2009 influenza A(H1N1).
Results The method could detect as few as 10-300 copies of each target plasmid DNA, and could only specifically detect the target virus but not other viruses in specimens. The application of the method in 849 throat swab specimens indicated that the overall positive rate was 39.0%, 1.4% for RSV-A, 8.4% for RSV-B, 8.2% for PIV-1, 0.5% for PIV-2, 3.9% for PIV-3, 13.9% for ADV, 2.7% for HBoV, respectively. In the tested positive cases, 87.6% cases were under 5 years of age. Statistical analysis of the data demonstrated that the dominated subtype of RSV was RSV-B (85.5%) which caused an epidemic peak from Nov. 2009 to Feb. 2010; PIV infections were mainly associated with PIV-1 from Jul. 2009 to Oct. 2009 and with PIV-3 from Jun. 2009 to Sep. 2009; ADV had a relatively high detectable rate during the whole period (an average of 13.9%); and the detectable rate of HBoV increased from Sep. 2009 to Dec. 2009.
Conclusions In addition to influenza virus, ADV, RSV-B and PIV infections were also associated with ARI in children during 2009 pandemic influenza A（H1N1）in Beijing. No evidence showed that the characteristics of both the seasonality and the morbidity of the viruses involving in this study were impacted by the pandemic of the new influenza virus H1N1.
Objective A molecular epidemiological study on rotavirus(HRV), human calicivirus(HuCV), astrovirus(AstV) and adenovirus(AdV) was conducted in stool specimen from patients with diarrhea under 5 years of age in Nanjing Children Hospital of Nanjing Medical University from July 2009 to June 2010, to provide the basic data and theory evidence for prevention and treatment of viral diarrhea.
Methods In Nanjing Children′s Hospital of Nanjing Medical University from July 2009 to June 2010, 300 stool specimens were collected from outpatients under 5 years of age diagnosed as diarrhea. HRV was detected by ELISA, strain characterization was carried out by nested PCR. HuCV (including norovirus and sapovirus), AstV and AdV were detected by RT-multiplex PCR or PCR.
ResultsIn the 300 children whose samples were collected, 188 patients were boys, 112 were girls. The age of children ranged from 1 to 59 months (mean±SD age: 10.5±9.2 months). At least one of the four viral agents was found in 60.0% (180/300) of the specimens. HRV, HuCV, AstV and AdV were identified in 37.7%（113/300）, 23.7% (71/300) , 4.0%(12/300), and 2.7%(8/300) in 300 specimens respectively. ①HRV G3 (38.9%) was the most prevailing serotype, followed by G2 (8.9%). Based on P typing, P［8］ (33.6%) was the most common genotype. The most common G-P combination was G3P［8］ (15.9%). The incidence of HRV infections peaked from October 2009 to January 2010, HRV was mostly found in children aged from 7 to 12 months. ②Of 71 HuCV positive samples, norovirus was detected in 67 cases and sapovirus was detected in 4 cases. HuCV infection peaked in August 2009, and was mostly found in children aged from 7 to 12 months. 95.8%(68/71) children aged under 24 months. ③Ten of 12 AstV infections occurred from October 2009 to January 2010, and AstV infected children were aged from 2 to 16 months. ④Of 8 AdV positive samples, there were seven serotypes: Ad31(2), Ad2(1), Ad3(1), Ad5(1), Ad7(1), Ad12(1) and Ad41(1). AdV infection peaked from January to June in 2010 and was mostly found in children aged from 7 to 12 months. ⑤Twenty-three of 300 samples were found positive to more than one viral agent, in which 12 samples contained both HRV and HuCV , and 5 samples contained both HRV and AstV, 1 sample contained both HRV and AdV, 2 samples contained both HuCV and AstV,1 sample contained both HuCV and AdV,1 sample contained both AstV and AdV, and 1 sample contained HRV, AstV and HuCV.
Conclusions The results indicated clearly the impact of viral agents in causing diarrhea in children and the importance of long-term systematic surveillance. HRV was also the most important pathogen, but HuCV, AstV and AdV should be given more attention.
Objective To investigate and compare the research topics of interventional diagnosis and therapy of congenital heart disease (CHD) through visualized structure networks based on path finder network (PFNET) analysis at home and abroad, point out the advantage and weakness of the native studies in this field.
Methods Medline database and China Biology Medicine disc (CBM) using MeSH keywords "heart defect, congenital" and "cardiac catheterization" were searched in March, 2011. After core key words had been charactered by Endnote X4 software, the co-occurrence matrix was built. After that, PFNET analysis was completed, leading the outside linking strength to be calculated. Then draw visualized network in Ucinet 6.0 software.
Results The search results included 3 000 and 1 015 articles in each database, which were imported into Endnote X4 software.The visualized structure of research topics was successfully built, and the structural differences between native and overseas researches were directly reflected. Clinic demands were the original driving force in both native and oversea research developments. The overseas research topics were more sufficient and fully developed, while the native researches showed more independent with less connection with open surgical procedure. And the characteristics of native researches were formed during the past 30 years with high speed development.
Conclusions Visualized structure networks based on PFNET analysis provide a systemic study about research topics of interventional diagnosis and therapy of CHD, intuitively illustrate the connections and developmental trends of the research topics in this field.
Objective To study the subject domain knowledge of interventional diagnosis and therapy of congenital heart disease (CHD) in our country using multiple statistical and social network analysis, and finally build visualized knowledge-mapping.
Methods The China Biology Medicine disc (CBM) using MeSH keywords "heart defect, congenital" and "cardiac catheterization" in March 2011 was searched. After core keywords had been characterized by Endnote X4, the co-occurrence matrix was built. Transformation, dimensionality reduction and clustering of the co-occurrence matrix were finished by SPSS 17.0 software, leading the strategic plot to be built.Then visualized network was drawn using Ucinet 6.0 software.
Results The searching results included 1 015 articles, which were imported into Endnote X4 software. The visualized domain knowledge-mapping was successfully built, and it directly reflected the structure of knowledge-mapping of the subject. And key clusters were formed, in which the "therapy", "method and instrument" and "echocardiography" clusters had been developed well.
Conclusions The "therapy" cluster stands in the center of the subject domain knowledge-mapping and is well developed with several clusters following. And the study of the "method and instrument" cluster makes a great contribution to the progress of the subject. The studies of echocardiography and pulmonary artery hypertension play an important role in the structure of the knowledge-mapping.
Objective To investigate the early diagnostic methods for renovascular hypertension(RVH) in children.
Methods Children diagnosed as RVH in Peking University First Hospital from January 1996 to July 2011 were included. The data including early diagnosis and treatment, age, gender, clinical characteristics and imaging examination results were collected and analyzed retrospectively.
Results Totally 29 children diagnosed as RVH were included aged from 0.5 to 15 years with a mean age of 7 years. There were 18 boys and 11 girls. The duration of diagnosis ranged from 15 days to 7 years, the average duration was 11 months. Nine children (31.0%) were diagnosed half year after some misdiagnosis such as gastritis, epilepsy, renal and cardiac diseases. Hypertension was found in 3 children due to convulsion after fluid injection. The most common onset symptoms included headache (34.5%), vomiting (34.5%), and convulsion (31.0%). The mean blood pressure was 182/127mmHg. Twenty five children were diagnosed as unilateral renal vascular stenosis and 4 children were diagnosed as bilateral renal vascular stenosis. Twenty three children were diagnosed by renal arterial angiography, 4 children were diagnosed by renal arterial ultrasound examination, 1 child was diagnosed by renal arterial ultrasound examination combined with computed tomography, 1 child was diagnosed by renal arterial ultrasound examination and MRA. Among the children diagnosed by renal angiography, the difference in bilateral renal size exceeded 1.5 cm in 10/17 children. The renal arterial ultrasound and CT examination detected 31.3%(5/16) and half (3/6) renal vascular hypertension respectively. Renography examination showed that 93.8% (15/16) of children with RVH had compromised renal function. Elevated serum renin and angiotensin were seen in 88.9%(16/18) patients. Hypokalemia was observed in 41.4% (12/29) of them. Ten children (34.5%) were diagnosed as Takayasu disease, 3 of them received nephrectomy, and 2 relapsed.
Conclusions The misdiagnosis of RVH patients was common. Blood pressure should be monitored for children with symptoms of headache, vomiting and convulsion especially before fluid injection. Renography was a sensitive method for detection of compromised renal function. For children with hypertension, renal ultrasound could be used as a screening tool. The difference of bilateral renal size exceeding 1.5 cm deserved further investigation of RVH. High serum renin and angiotensin and hypokalemia had suggestive roles for RVH. Renal arterial ultrasound and CT examinations were not sensitive enough. For children who were suspected as RVH, renal arterial angiography should be performed as early as possible. Etiology diagnosis should be made especially for Takayasu arteritis.
Objective To summarize the results of 8 cases with bronchopulmonary dysplasia (BPD) for 6 years clinical follow-up study.
Methods Eight cases with BPD born at the Affiliated Yuying Children′s Hospital of Wenzhou Medical College from January 2004 to December 2005 were contacted by out-patient follow-up or telephone at the age of 1, 3 and 6 years in order to explore the long-term outcome of BPD.
Results Three cases of BPD children were contacted by telephone at 1 year old and 5 cases were contacted by out-patient follow-up at this age. Two cases of BPD children were contacted by telephone at 3 years old and 6 cases were contacted by out-patient follow-up at this age. Eight cases of BPD children were all contacted by out-patient follow-up at 6 years old. The re-hospitalization times were 22, 6 and 1 due to recurrent pneumonia or acute bronchitis at the age of 1, 3 and 6 years, respectively. The wheezing times were 10 (4 cases), 6 (3 cases) and 3 (2 cases) at the age of 1, 3 and 6 years, respectively. Pulmonary function tests showed abnormalities in 5 cases (62.5%), including small airway changes, mild obstructive ventilatory dysfunction, etc. Chest radiography showed ground grass opacity, vesicle formation in 3 cases, thickness or turbulence of texture in bilateral lungs, irregular opacity in 3 cases and local emphysema in 2 cases.
Conclusions BPD significantly increased the risk of re-hospitalization after birth. It occurred commonly at the age of 1 year and decreased at pre-school age.Clinical follow-up at the age of 6 years found that 62.5% of the cases showed abnormal pulmonary function,and the characteristics of ground grass opacity, vesicle formation and local emphysema in chest image.
Objective To describe the clinical features and outcome of Wegener′s granulomatosis in children.
Methods A retrospective study of 10 patients diagnosed as Wegener′s granulomatosis was conducted at Department of Pediatrics, Peking Union Medical College Hospital from October 1990 to July 2010 to analyze the clinical manifestations, examination results, pathological data, treatment and outcome.
Results Of 10 patients, 6 were males and 4 were females. The ages of patients at disease onset varied from 7 to 17.1 years. The median age was 13.9 years. Time for diagnosis ranged from 2 to 24 months and follow-up time ranged from 4 months to 19 years. ①Seven children presented with fever at disease onset, fatigue in 3 patients and weight loss in 2 patients. Upper airway involvement occurred in all patients. Eight patients had pulmonary involvement. Renal involvement occurred in 4 patients. Joints, skin, eyes and nervous system were rarely involved. ②c-ANCA positive reaction was seen in 8 patients. ③Sinus imaging studies were taken in 9 patients, sinusitis in 4 patients, sinus mass in 3 patients and violation of eyes in 2 patients. Eight patients underwent chest CT examination, multiple pulmonary nodules with or without cavity formation in 5 patients, invasive lesions in 2 patients, and pleural effusion in 1 patient. Brain MRI showed ischemic changes in 2 patients. ④Pathological examination (7 nasal mucosa samples, 2 lung samples, 1 kidney sample) showed necrotizing granuloma and (or) vasculitis. ⑤All children were given corticosteroids and cyclophosphamide at the beginning of treatment. Treatment was changed to use glucocorticoid and methotrexate in 2 patients and 1 patient was given cyclosporine A. All patients were remitted after treatment. ⑥Seven patients relapsed, 1 patient had renal insufficiency and 1 patient died of respiratory failure during the period of follow-up.
Conclusions The upper respiratory tract, lung and kidney were the most commonly involved organs in Wegener′s granulomatosis. Positive c-ANCA and pathological examination were helpful to the diagnosis. Treatment with corticosteroid and immunosuppressive could achieve good outcome.
Objective To analyze the effect of GH therapy on idiopathic short stature (ISS) patients and the influential factors.
Methods Patients who accepted rhGH therapy and regularly revisited were chosen as rhGH group, and patients who didn′t accept rhGH therapy as control group. Growth velocity (GV) and increment in height SDS (ΔHtSDS) were used as outcome variables of growth responses to rhGH therapy. Then the effect and influential factors or the changes on those untreated such as bone age, height age were retrospectively analyzed during the follow-up.
Results Thirty-five patients were recruited in rhGH group and 33 patients in control group. The ΔHtSDS and GV of patients in rhGH group during the first 3 months, -6 months, -9 months, -12 months were (0.22±0.13), (0.20±0.10), (0.12±0.14), (0.14±0.15) and (10.78±2.70) cm, (10.52±2.44)cm, (8.31±2.78)cm, (8.50±2.29) cm respectively. The height increments in the first 6 months and 6-12 months were 5.24 cm (0.43 SDS) and 4.24 cm (0.26 SDS), it was 9.54 cm (0.68 SDS) in the first year and 7.00 cm (0.17 SDS) in the second year. According to the simple correlation analysis, it was found that ΔHtSDS in the first year was negatively correlated with patients′ age and positively correlated with ΔHtSDS in 3 months after treatment, GV levels in first year were negatively correlated with the peak of GH level and GV in 3 months after treatment. There were significant differences in ΔHtSDS among prepubertal, midpubertal and postpubertal children one year after treatment(P=0.016), ΔHtSDS was significantly higher in prepuberty than midpuberty and postpuberty. But there was no significant difference in GV. Besides, the increment of height age in rhGH group was significantly larger than control group, but there was no significant difference in increment of bone age between two groups. The levels of IGF-1 elevated in rhGH group signigicantly 1 month after treatment and slowed down afterwards.
Conclusions For ISS patients, therapy should be started at an earlier age ,at least before the puberty in order to achieve better cost-effect ratio. The therapeutic effect in the first 3 months may be a good predictor of one year therapeutic efficacy. While the rhGH therapy didn′t significantly accelerate the increment of bone age of patients.
