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Vol 15, No 6
Vol 15, No 6 December 2019 ISSN 1708-8569
Review articles
Original articles
Brief reports
Letters to the editor
Review articles:
Gianotti每Crosti syndrome (papular acrodermatitis of childhood) in the era of a viral recrudescence and vaccine opposition
  Alexander K. C. Leung, Consolato Maria Sergi, Joseph M. Lam, Kin Fon Leong
Background: Gianotti每Crosti syndrome is characterized by an acute onset of a papular or papulovesicular eruption with a symmetrical distribution.
Data sources: A PubMed search was conducted using Clinical Queries with the key terms ※Gianotti-Crosti syndrome§ OR ※papular acrodermatitis§. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. This paper is based on, but not limited to, the search results.
Results: The eruption of Gianotti每Crosti syndrome is found predominantly on the cheeks, extensor surfaces of the extremities, and buttocks. There is a sparing of antecubital and popliteal fossae as well as palms, soles, and mucosal surfaces. Although often asymptomatic, the lesions may be mildly to moderately pruritic. Gianotti每Crosti syndrome is most common in children between 1 and 6 years of age. The Epstein每Barr virus and the hepatitis B virus are the most common pathogens associated with Gianotti每Crosti syndrome. No treatment for Gianotti每Crosti syndrome is necessary because it is self-limited. In an era of vaccine hesitancy and refusal, Gianotti每Crosti syndrome may be important to mention to parents, because it can occur and trigger alarmism.
Conclusions: Gianotti每Crosti syndrome is mainly a disease of early childhood, characterized by an acute onset of a popular or papulovesicular eruption with a symmetrical distribution. With the advent of more universal vaccination against hepatitis B virus, Epstein每Barr virus has become the most common etiologic agent of Gianotti每Crosti syndrome. Few cases of post-vaccination Gianotti每Crosti syndrome have been reported. Currently, the emphasis should be placed on its self-limiting attribution.
  [Abstract] [Full Text] [PDF]  
Kabuki syndrome: review of the clinical features, diagnosis and epigenetic mechanisms
  Yi-Rou Wang, Nai-Xin Xu, Jian Wang, Xiu-Min Wang
Background: Kabuki syndrome (KS), is a infrequent inherited malformation syndrome caused by mutations in a H3 lysine 4 methylase (KMT2D) or an X-linked histone H3 lysine 27 demethylase (UTX/KDM6A ). The characteristics in patients with KS have not yet been well recognized.
Data sources: We used databases including PubMed and Google Scholar to search for publications about the clinical features and the etiology of Kabuki syndrome. The most relevant articles to the scope of this review were chosen for analysis.
Results: Clinical diagnosis of KS is challenging in initial period, because many clinical characteristics become apparent only in subsequent years. Recently, the genetic and functional interaction between KS-associated genes and their products have been elucidated. New clinical findings were reported including nervous system and intellectual performance, endocrine-related disorders and immune deficiency and autoimmune disease. Cancer risks of Kabuki syndrome was reviewed. Meanwhile, we discussed the Kabuki-like syndrome. Digital clinical genetic service, such as dysmorphology database can improve availability and provide high-quality diagnostic services. Given the significant clinical relevance of KS-associated genes and epigenetic modifications crosstalk, efforts in the research for new mechanisms are thus of maximum interest.
Conclusions: Kabuki syndrome has a strong clinical and biological heterogeneity. The main pathogenesis of Kabuki syndrome is the imbalance between switch-on and -off of the chromatin. The direction of drug research may be to regulate the normal opening of chromatin. Small molecule inhibitors of histone deacetylases may be helpful in treatment of mental retardation and reduce cancer risk in KS.
  [Abstract] [Full Text] [PDF]  
Childhood Langerhans cell histiocytosis: a disease with many faces
  Alexander K. C. Leung, Joseph M. Lam, Kin Fon Leong
Background: Langerhans cell histiocytosis (LCH) is a group of diseases characterized by the proliferation and accumulation of Langerhans cells. Clinical presentations of LCH vary widely.
Data sources: A PubMed search was conducted using Clinical Queries with the key term ※Langerhans cell histiocytosis§. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. This paper is based on, but not limited to, the search results.
Results: Generally, patients with LCH can be divided into two groups based on the extent of involvement at diagnosis, namely, single-system LCH and multisystem LCH. The involvement may be unifocal or multifocal. Patients with isolated bone lesions typically present between 5 and 15 years of age, whereas those with multisystem LCH tend to present before 5 years of age. The clinical spectrum is broad, ranging from an asymptomatic isolated skin or bone lesion to a life-threatening multisystem condition. Clinical manifestations include, among others, "punched out" lytic bone lesion, seborrheic dermatitis-like eruption, erythematous/reddish-brown crusted/scaly papules/maculopapules/plaques/patches, and eczematous lesions, diabetes insipidus, hepatosplenomegaly, cytopenias, lymphadenopathy, and an acute fulminant disseminated multisystem condition presenting with fever, skin rash, anemia, thrombocytopenia, lymphadenopathy, and hepatosplenomegaly. The diagnosis is clinicopathologic, based on typical clinical findings and histologic/immunohistochemical examination of a biopsy of lesional tissue. Positive CD1a, S100, and/or CD207 (Langerin) immunohistochemical staining of lesional cells is required for a definitive diagnosis. Watchful waiting is recommended for patients with skin-only LCH. Patients with symptomatic or refractory skin-only LCH may be treated with topical tacrolimus/corticosteroids, topical nitrogen mustard, oral methotrexate, or oral hydroxyurea. The current recommended first-line therapy for patients with multisystem LCH is 12 months therapy with prednisone and vinblastine. Mercaptopurine is added for patients with risk organ involvements.
Conclusions: Because of the broad spectrum of clinical manifestations and the extreme diversity of disease, LCH remains a diagnostic dilemma. Morphological identification of LCH cells and positive immunochemical staining with CD1a, S100, and/or CD207 (Langerin) of lesional cells are necessary for a definitive diagnosis.
  [Abstract] [Full Text] [PDF]  
Efficacy and adverse effects of oral propranolol in infantile
  Hao Yang, Dong-Lai Hu, Qiang Shu, Xiao-Dong Guo
Background: A number of clinical trials evaluated the efficacy and adverse effects of oral propranolol in the treatment of infantile hemangioma (IH), but the treatment has not yet been standardized. This meta-analysis aims to reevaluate the efficacy and adverse effects of oral propranolol in comparative studies and to provide a reliable basis for clinical administration in the therapy for IH.
Methods: Data were obtained from PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure and Wanfang database, from inception to December 1st, 2018. The pooled risk ratios (RR) with 95% confidence intervals (95% CI) were calculated and used to evaluate the effect size. The meta-analysis was performed using the random-effects model due to heterogeneity between the studies. The Cochrane Collaboration 6 aspects of bias, methodological index for non-randomized studies and the Newcastle每Ottawa Scale were used to assess the risk for bias. Sensitivity analysis, publication bias and subgroup analysis were performed.
Results: Eighteen unique studies involving 2701 unique children were included in the analysis. The response rate was reported in 18 trials, which compared oral propranolol with other treatments. The heterogeneity was statistically significant (P < 0.00001, I2 = 95%). The difference in the response rate was statistically significant (RR = 1.40, 95% CI 1.13每1.75) while compared with the controls. However, no significant difference in the adverse events rate (RR = 0.78, 95% CI 0.45每1.34) and relapse rate (RR = 1.45, 95% CI 0.66每3.16) were found. Otherwise, the subgroup analysis indicated that the RR was 1.64 (95% CI 0.24每11.36) for low-dose propranolol (1 mg/kg/day), 1.42 (95% CI 1.12每1.80) for medium dose (2 mg/kg/day) and 1.46 (95% CI 1.17每1.82) for high dose (3 mg/kg/day), but the high dose had higher adverse events rate than medium dose, with 3.60% and 86.22%, respectively. The effectiveness of propranolol therapy among cases of treatment duration less than 6 months (RR = 1.24, 95% CI 1.05每1.47) was inferior to that of treatment duration greater than or equal to 6 months (RR = 1.46, 95% CI 1.11每1.92).
Conclusions: This meta-analysis reveals that oral propranolol is superior to other treatments in improving response rate of IH and can be used as the first-line therapy for IH children. A dosage of 2 mg/kg/day propranolol orally may be a good choice for IH. However, further studies are essential.
  [Abstract] [Full Text] [PDF]  
Original articles:
A clinical study to determine the threshold of bronchodilator response for diagnosing asthma in Chinese children
  Xiao-Hui Kang, Wan Wang, Ling Cao
Background: There is few objective, clinically feasible and inexpensive test for diagnosing childhood asthma. We want to find an ideal way to solve it.
Methods: The control group was 301 non-asthmatic children, and the asthma group was 286 asthmatic children. The asthmatic children were divided into three groups according to the severity of their disease. Pre- and post-bronchodilator spirometer tests were performed, and the main spirometer parameters were compared. The bronchodilator response (BDR) [BDR is used to determine the reversibility of airway obstruction by measuring the changes of forced expiratory volume in the first second (FEV 1) before and after inhalation of bronchodilators] was then determined, and the optimal threshold of BDR for diagnosing childhood asthma was found.
Results: 301 non-asthmatic children and 286 asthmatic children participated in the study, the demographics were similar. FEV1 for pre-bronchodilator of asthmatic children was significantly lower than that of non-asthmatic children (P ≒ 0.01). BDR of non-asthmatic children was 3.30 ㊣ 3.85%. BDR of asthmatic children was 9.45 ㊣ 9.15%. There was no significant difference in BDR for patients with different severities of asthma within the group. BDR had no statistical correlation with gender, age, height, weight in neither non-asthmatic children nor asthmatic children. On the receiver-operating characteristic curve, a BDR threshold of ≡ 7.5% offered an optimal balance in asthma diagnosis with a sensitivity rate of 50.7% and specificity rate of 87.7%. Meanwhile, with a BDR threshold of ≡ 12%, the sensitivity rate was 28.7% and the specificity rate was 96.3%.
Conclusion: A BDR threshold of ≡ 7.5% has more value in childhood asthma diagnosis as compared to ≡ 12%.
  [Abstract] [Full Text] [PDF]  
Adropin and glucagon-like peptide-2 are associated with glucose metabolism in obese children
  Rui-Min Chen, Xin Yuan, Qian Ouyang, Xiang-Quan Lin, Zhuan-Zhuan Ai, Ying Zhang, Xiao-Hong Yang
Background: The interaction of adropin, glucagon-like peptide-2 (GLP2), angiopoietin-like protein 4 (ANGPTL4), and with childhood obesity and glucose metabolism is inconsistent. This study is to evaluate the association of the three cytokines and glucose homeostasis.
Methods: This was a cross-sectional study of children with obesity ranging from 5 to 14 years compared to age- and sex-matched children of normal weight. Fasting plasma glucose (FPG), oral glucose tolerance test 2-hour plasma glucose (OGTT2hPG), and insulin (INS) were measured, and serum adropin, GLP2, and ANGPTL4 levels were measured by enzymelinked immunosorbent assay. The body mass index (BMI), BMI-Z scores, waist-to-hip ratio (WHR), and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated.
Results: Thirty-nine children (9.70 ㊣ 1.71 years, 18 females) with obesity and 29 normal weight children (8.98 ㊣ 1.98 years, 16 females) were assessed. The levels of INS, HOMA-IR and GLP2 of the obesity group were significantly higher than the controls (P < 0.05). Pearson correlation analysis showed that serum GLP2 was positively associated with WHR, FPG, and OGTT2hPG, and adropin was negatively associated with BMI, BMI-Z, WHR, INS, and HOMA-IR (all P < 0.05). Furthermore, GLP2 were negatively associated with adropin and ANGPTL4 (both P < 0.05). By binary logistic regression, adropin and GLP2 were found to be independent markers of obesity. Multiple linear regression showed that GLP2 was associated with OGTT2hPG, and adropin was associated with INS and HOMA-IR (all P < 0.05).
Conclusions: Obese children had elevated GLP2 concentrations, and adropin and GLP2 associated with both childhood obesity and glucose homeostasis. Furthermore, there may be a physiologic interplay between adropin and GLP2 in obese children.
  [Abstract] [Full Text] [PDF]  
Association of image-defined risk factors, tumor resectability, and prognosis in children with localized neuroblastoma
  An-An Zhang, Ci Pan, Min Xu, Xiao-Xia Wang, Qi-Dong Ye, Yi-Jin Gao, Jing-Yan Tang
Background: Although localized neuroblastoma has a good prognosis, some cases have undergone treatment failure or recurrence. Apart from biologic features such as MYCN status, we wondered whether some characteristics of growing tumors are prognostic, such as a well-encapsulated mass without infiltration of vital organs. We analyzed the diagnostic utility of image-defined risk factors (IDRFs) to predict successful treatment and prognosis. The overall goal was to achieve maximum cure rates for patients with localized neuroblastoma through a better understanding of clinical characteristics.
Methods: We retrospectively reviewed the images of patients with localized neuroblastoma who were enrolled between June 1998 and December 2012 at a single institution in Shanghai, China. Unequivocal categorization regarding IDRFs was available in 67 patients. IDRF was assessed at diagnosis and after four cycles of neoadjuvant chemotherapy, on average. The median follow-up period was 84 months (range: 48每132 months) after diagnosis.
Results: MRI and CT indicated a total of 177 IDRFs in these 67 patients. Logistic regression analysis revealed a highly significant negative correlation between the numbers of IDRFs and the possibility of complete removal of neuroblastoma. Intraspinal extension of the tumor, compression of the trachea, and encasement of the main artery in localized neuroblastoma were predictors for incomplete tumor resection. According to univariate analysis, ≡ 4 IDRFs and intraspinal extension of the tumor were significant indicators of poor prognosis.
Conclusions: The number of IDRFs was useful in predicting surgical outcome and event-free survival. The number of IDRFs should be considered in protocol planning, instead of IDRF presence or absence.
  [Abstract] [Full Text] [PDF]  
Community-acquired serious bacterial infections in the first 90 days of life: a revisit in the era of multi-drug-resistant organisms
  Dawood Yusef, Tamara Jahmani, Sajeda Kailani, Rawan Al-Rawi, Wasim Khasawneh, Miral Almomani
Background: Infants in the first 90 days of life are more prone to develop serious bacterial infections (SBIs). Multi-drug-resistant organisms (MDROs) are emerging as important pathogens causing SBIs. We reviewed the epidemiology of SBIs in infants 0每90 days old and compared the clinical features, laboratory values and final outcome for SBIs due to MDROs vs. non-MDROs.
Methods: Episodes of culture-proven SBIs (bacteremia, urinary tract infections, or meningitis) with age at onset of 0每90 days during a 7-year period were retrospectively reviewed. Health care-associated infections were excluded. We collected demographics, clinical features, and laboratory and microbiology data. We compared clinical characteristics, laboratory data, microbiologic results and final outcome for SBIs due to MDROs vs. non-MDROs.
Results: Ninety-four episodes (88 patients) including bacteremia (42.6%), urinary tract infections (54.3%) and meningitis (3.1%) were caused by Gram-negative bacteria (67%), and Gram-positive bacteria (33%). Escherichia coli, Klebsiella pneumoniae and GBS were the most common causes. MDROs caused SBIs in 39 patients (44.3%). SBIs due to MDROs were associated with more delay in providing targeted antimicrobial therapy compared to non-MDROs (74.4% vs. 0%, P ≒ 0.001), but no difference in case-fatality rate (12.8% vs. 12.2%, P = 1.0). Clinical features or basic laboratory values were not statistically different between the two groups.
Conclusions: The bacteriology of SBIs in the first 90 days of life is changing to include more MDROs, which causes more delay in providing targeted antimicrobial therapy. Awareness of the local epidemiology is crucial to ensure appropriate antibiotics are provided in a timely manner.
  [Abstract] [Full Text] [PDF]  
Inpatient use of racemic epinephrine for children admitted with croup
  Elaine Chiang, Omar Afandi, Sang Hoon Lee, Srinivasan Suresh, Raymond D. Pitetti, Sriram Ramgopal
Background: Pediatric patients with croup are frequently admitted if they require two doses of racemic epinephrine (RE) in the emergency department (ED). We aimed to identify factors associated with the need for additional therapy (> 2 RE doses) among pediatric patients with croup.
Methods: We performed a single-center retrospective study of consecutive patients admitted from the ED with a diagnosis of croup between January 1, 2011 and December 31, 2015. Primary outcome was need for > 2 doses of RE. Secondary outcomes included time to third RE and 72-hour return visits. We performed logistic regression to identify factors associated with use of > 2 RE doses during hospitalization, and survival analysis to identify time to dosing of 3rd RE from 2nd RE.
Results: Of 353 included admissions [250 (70.8%) males, median age 1.48, interquartile range 0.97每2.51 years], 106/353 (30.0%) required > 2 RE. In univariate logistic regression, only recent use of steroids within 1 day prior to presentation (4.18, 1.48每11.83; P = 0.007) was associated with need for > 2 RE. Survival from third RE was 0.74 (95% CI 0.69每0.78), which was similar to the survival at 12 hours (0.70, 95% CI 0.65每0.75). Return visits occurred in 19 (5.4%) patients, of whom 12/19 (63.2%) were given RE.
Conclusions: Patients hospitalized for croup with recent use of steroids prior to ED presentation have a greater need for > 2 RE during hospitalization. The majority who require inpatient RE will do so within 8每12 hours. These data provide information for risk stratification and duration of monitoring for patients hospitalized with croup.
  [Abstract] [Full Text] [PDF]  
Efficacy and safety of interferon alpha-2b versus pegylated interferon alpha-2a monotherapy in children with chronic hepatitis B: a real-life cohort study from Shanghai, China
  Yao Hu, Ying-Zi Ye, Li-Jing Ye, Xiao-Hong Wang, Hui Yu
Background: Interferon alpha (IFN-汐) is a preferred therapy for antiviral treatment of children with chronic hepatitis B (CHB) aged > 1 year currently. Peginterferon alpha-2a (Peg-IFN 汐-2a) is a recommended international guideline for treatment of CHB children, which is limited to children aged > 3 years. But the exact efficacy and safety of IFN-汐 and Peg-IFN 汐-2a for treating CHB are not sufficient.
Methods: Clinical manifestations, baseline characteristics, related laboratory tests and adverse events were retrospectively analyzed in children with CHB, who visited Children*s Hospital of Fudan University and were treated with IFN 汐-2b or Peg-IFN 汐-2a monotherapy and followed up from January 2003 to October 2018.
Results: A total of 36 immune-active patients without advanced fi brosis were enrolled to be treated with IFN 汐-2b (group A, n = 18) or Peg-IFN 汐-2a (group B, n = 18). IFN 汐-2b or Peg-IFN 汐-2a was administered for a median of 48 weeks subcutaneously by body surface area (BSA) category at a dose of 3 MU/m2 or 104 米g/m2, respectively. HBV e antigen (HBeAg) seroconversion rates at 48 weeks post-treatment were higher in group A than group B (92.9% vs. 87.5%), so as the rates of HBsAg clearance (22.2% vs. 11.1%), and hepatitis B virus (HBV)-DNA < 1000 IU/mL (88.9% vs. 83.3%). Only mild flu-like symptoms and transient neutropenia appeared in some children at the early stage of treatment. No severe abnormal results was observed in other laboratory assessments.
Conclusion: The antiviral monotherapy of 48-week IFN 汐-2b or Peg-IFN 汐-2a in children with CHB is well tolerated and effective, which is associated with higher rates of HBeAg seroconversion and HBsAg clearance than in adults and previously pediatric patients.
  [Abstract] [Full Text] [PDF]  
Factors associated with exclusive breastfeeding in relation to knowledge, attitude and practice of breastfeeding mothers in Rabigh community, Western Saudi Arabia
  Moustafa A. Hegazi, Mousa Allebdi, Mohammed Almohammadi, Abdulelah Alnafie, Lama Al-Hazmi, Shahad Alyoubi
Background: There is much concern about declining rates of exclusive breastfeeding (EBF) all over the world including Saudi Arabia which deprives infants from many immunological, nutritional, and psychosocial benefits. This study was performed to determine EBF prevalence and factors influencing EBF in relation to knowledge, attitude and practice (KAP) of breastfeeding mothers (BFM) in Rabigh, Western Saudi Arabia.
Methods: Data about factors that could be associated with EBF and KAP of BFM were collected by cross-sectional questionnaire-based study from 420 BFM.
Results: Prevalence of EBF for 6 months was 27.6% which is far below World Health Organization recommendations. Demographic, socioeconomic, biomedical as well as most studied variables of KAP of 50% to over 90% of participating mothers were adequate to account for low EBF rate. Proper knowledge about benefits of colostrum and continuation of breastfeeding for 2 years was given by only 86.2% and 36.7% of BFM, respectively. The most significant independent factors associated with EBF were perception of sufficient human milk [adjusted odds ratio (AOR) 2.89; 95% confidence interval (CI) 1.72每4.89], absence of nipple pain (AOR 2.77; 95% CI 1.72每4.45) and mothers without university education (AOR 1.86; 95% CI 1.15每3.01). Early introduction of formula in hospital after birth was the main inappropriate feeding practice in 76.2% of infants of BFM.
Conclusion: Findings of this study should be utilized by Rabigh community and other national or worldwide communities with similar characters to promote EBF by targeted educational programs after identification of significant factors influencing EBF and gaps in KAP of BFM.
  [Abstract] [Full Text] [PDF]  
Brief reports:
Optimization and application of a dried blood spot-based genetic screening method for thalassemia in Shenzhen newborns
  Wei Wen, Meng Guo, Hong-bing Peng, Li Ma
Background: To optimize and apply an approach suitable for large-scale neonatal thalassemia genetic screening in China, thalassemia genotypes were determined by polymerase chain reaction-reverse dot blot using DNA extracted from dried blood spots (DBS) obtained from newborn screening programs.
Methods: Firstly, the most suitable commercial DNA extraction kit for DBS was screened. Then, the appropriate amount of DBS required for the automated high-throughput DNA extraction system was evaluated. Finally, the thalassemia prevalence and genotype spectrum in Shenzhen were investigated in 2028 newborns using the optimized screening procedure.
Results: The Magentec extraction kit was best suited for the automated DBS DNA extraction system using eight 3-mm DBS discs. The neonatal thalassemia prevalence in Shenzhen was 9.12%; 6.31% 汐-thalassemia, 2.37% 汕-thalassemia, and 0.44% 汐-/汕-thalassemia.
Conclusions: Genetic screening based on DBS can precisely identify the thalassemia genotypes. Both 汐- and 汕-thalassemia are widely distributed in Shenzhen newborns. Newborn genetic screening is important for establishing a comprehensive thalassemia prevention program and for public education.
  [Abstract] [Full Text] [PDF]  
Is a nasogastric tube necessary after transumbilical laparoscopic-assisted appendectomy in children with perforated appendicitis?
  Akinori Sekioka, Koji Fukumoto, Toshiaki Takahashi, Hiromu Miyake, Kengo Nakaya, Akiyoshi Nomura, Yutaka Yamada, Naoto Urushihara
Background: This study assessed the necessity of postoperative nasogastric tube (NGT) use in acute pediatric cases of perforated appendicitis.
Methods: All cases of acute pediatric perforated appendicitis managed with transumbilical laparoscopic-assisted appendectomy at our hospital from 2011 to 2017 were retrospectively reviewed. Sixty-two cases were selected and divided into two groups based on NGT placement.
Results: There were no significant differences between the two groups in most parameters of patient demographics, or surgical data. Notably, the mean time to first oral intake and to regular diet was significantly shorter in no-NGT group (1 day vs 3 days, P < 0.0001; and 4 days vs 7 days, P = 0.003, respectively). Postoperative length of stay was significantly shorter in no-NGT group (7 days vs 9 days, P < 0.0001).
Conclusion: Considering the results of our analysis, we believe that routine NGT placement is not always necessary in these situations.
  [Abstract] [Full Text] [PDF]  
Letters to the editor:
What should professionals do for the parents of children with ADHD?
  Shu-Jiong Mao, Jian Shen
  [Abstract] [Full Text] [PDF]  
Acute poisoning: an old-time classic issue in pediatrics
  Despoina Gkentzi, Xenophon Sinopidis, Diamanto Gourdoupi, Manolis Mentis, Ageliki Karatza, Gabriel Dimitriou
  [Abstract] [Full Text] [PDF]  
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