Several fatal events occurred in Hunan, Guangdong and Sichuan Province in December, 2013. The events were reported by the news media, which followed growing public concern. Currently, more and more vaccines were developed and the immunization was adopted for more objectives. The clinicians, especially pediatricians will face a growing number of clinical problems related to the vaccine. The clinicians should pay attention to learn more knowledge about vaccines. This article describes the definition and classification of "adverse events following immunization" and "serious vaccine product-related reactions", and the signifcance and conclusion of causality assessment following immunization.

Malnutrition is not a simple disease, which occurs in the condition when the body does not get the right amount of nutrients to maintain healthy tissues and organ functions. Malnutrition generally refers both to undernutrition and overnutrition, but usually it is used to refer solely to a deficiency of nutrition. Infants and young children are the most vulnerable because of their high nutritional requirements for growth and development. Growth is an important indicator of health and nutritional status of a child. Generally, underweight, studding and wasting are used as the indicators of malnutrition. In fact, a gain in height is a better indicator of the adequacy of a diet than a gain in weight. Rates of weight gain needs to accompany accelerated height gain to maintain normal body proportions (weight-for-height). Now therefore WHO recommends using weight-for-height as the indicator of malnutrition of epidemic intensity in communities and of nutritional condition evaluation, including treatment assessment. The assessment of nutritional status is commonly summarized by the mnemonic "ABCD", which stands for anthropometric measurement (A), biochemical or laboratory tests (B), clinical indicators (C) and dietary assessment (D). Children with malnutrition are required to ingest more than 30 essential nutrients including both functional, protective nutrients (type I) and growth nutrients (type Ⅱ), in order to have a catch-up growth in weight and height.

Objective To evaluate the efficacy and safety of a phenylalanine-free amino acid-based enteral formula (AA-PKU2) in the treatment of children with phenylketonuria (PKU) aged 1-8 years. Methods A prospective, open, self-controlled, multi-center trial was performed, enrolling 121 PKU children (1-8 years in age) consecutively between July, 2009 and May, 2011. Enteral nutrition therapy was administered for 32 weeks. The data on blood phenylalanine (PHE) levels, metal development, weight, height, head circumference, serum nutritional biomarkers (total protein, pre-albumin, albumin, total cholesterol, total triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol), and measurements from routine blood and urine examinations and from renal and hepatic function tests were collected before the therapy and at 8 weeks and 32 weeks after the therapy and were comparatively analyzed. Results The mean blood PHE level at 8 and 32 weeks of AA-PKU2 treatment was 353±253 and 361±280 μmol/L respectively, significantly lower than that before the treatment (487±327 μmol/L; P<0.01). The difference in intelligence quotient scores before and after AA-PKU2 treatment was not significant (P >0.05) when assessed by the Gesell tests in children aged 1-4 years but significant (P<0.01) when assessed by WPPSI or WISR-R tests in children over 4 years. The average height, weight and head circumference at 8 and 32 weeks after treatment were significantly increased as compared to these measurements before treatment (P<0.01) with absolute levels similar to those in the control children. In contrast, the mean values of total protein, pre-albumin, albumin, total cholesterol, total triglyceride, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol at both time points were not different either from those prior to the treatment or from those in the control children. Mild diarrhea was the adverse events associated with AA-PKU2 treatment, which occurred in 3 (2.5%) cases. All these 3 patients fully recovered without treatment. Conclusions The phenylalanine-free amino acid-based formula, AA-PKU2, is effective and safe in controlling blood PHE levels and improving mental development with adequate nutritional support in PKU.

Objective To investigate the clinical features of nutritional iron deficiency anemia (IDA) and analyze the risk factors for the severity of anemia, and to provide a basis for the prevention and clinical diagnosis and treatment of this disease. Methods A retrospective analysis was performed on the clinical data of 372 children with IDA to investigate the risk factors for the severity of IDA. Results Of 372 cases, the male-to-female ratio of these patients was 2.72:1. Of all cases, 79.9% were aged 6 months to 2 years, and 30.7% were premature infants; 22.9% had a birth weight of < 2.5 kg, and 77.1% had a birth weight of ≥2.5 kg; 36.0% were delivered by natural birth, and 64.0% were delivered by caesarean section; 79.3% were not given solid foods in time; 46.2% had a history of lower respiratory tract infection/recurrent upper respiratory tract infection, diarrhea, trauma, or surgery. The univariate analysis showed that age, birth weight, gestational age, timely introduction of solid foods, and a history of lower respiratory tract infection/recurrent upper respiratory tract infection, diarrhea, trauma, or surgery were associated with the severity of anemia. The multivariate analysis showed that birth weight and the mentioned medical history were associated with the severity of anemia. Conclusions Nutritional IDA is common in children aged 6 months to 2 years. Nowadays, improper feeding pattern is still one of the main causes of IDA. Birth weight and a history of lower respiratory tract infection/recurrent upper respiratory tract infection, diarrhea, trauma, or surgery are closely associated with the severity of anemia.

Objective To investigate the relationship of leptin gene polymorphism with obesity in ethnic minority Hui and Uygur children in China. Methods Sixty-eight ethnic minority (35 Hui and 33 Uygur) children with obesity and 69 age-matched minority (36 Hui and 33 Uygur) children without obesity were recruited from six primary schools in the sub-urban areas of Urumqi. Venous blood was sampled from all subjects after fasting for 12 hours. Leptin gene C2549A polymorphism was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism methods. Blood concentrations of lipids, leptin and insulin were measured with biochemical methods and radioimmunoassys, respectively. Results In the 137 children tested, the prevalence of AA, AC and CC genotype was 9.5%, 33.6% and 56.9%, respectively. A allele frequency was significantly different between the two ethnic (i.e. Hui and Uygur) groups (P<0.05). A allele frequency and AA+ AC genotype frequency were not significantly different between obese and non-obese children in both ethnic groups (P >0.05). Blood leptin levels were not significantly different between obese and non-obese children with an AA+AC or CC genotype in both ethnic groups (P >0.05). Conclusions Leptin gene polymorphisms exist in Hui and Uygur children. The C2549A polymorphism is not significantly associated with the prevalence of obesity in both Hui and Uygur children.

Objective To determine the effect of gonadotropin releasing hormone agonist (GnRHa), by itself alone or in combination with recombinant human growth hormone (rhGH), on height in young girls (bone age≥10 years) with idiopathic central precocious puberty (ICPP). Methods Eighty girls with ICPP (9.0±0.7 years old) from six medical centers across Southeast and Southwest China participated in this study. They were allocated to treatment with GnRHa+rhGH (n=31) and GnRHa (n=49) respectively. Girls in the GnRHa+rhGH group (bone age 11.18±0.53 years) were treated with GnRHa for 25.29±6.92 months and rhGH for 12.87±7.02 months. Girls in the GnRHa group (bone age 11.03±0.50 years) were treated with GnRHa for 25.96±8.95 months. The height standard deviation for bone age (HtSDS-BA), predicted adult height, near-adult height and net height increase before and after treatment were recorded for girls in both groups. Results HtSDS-BA was significantly improved after treatment for both groups (P<0.01) and the HtSDS-BA value was superior in the GnRHa+rhGH group over the GnRHa group (P<0.01). Values in near adult height (157±6 cm vs 157±4 cm), net height increase after treatment (4.68 cm vs 3.89 cm), and predicted adult height after drug withdrawal (161±5 cm vs 158±5 cm) were higher in the GnRHa+rhGH group than the GnRHa group, but the differences were not significant. Conclusions Both GnRHa plus rhGH and GnRHa alone can improve the near adult height in girls with ICPP with a bone age ≥10 years to a similar extent. Adult height predicted based on bone age in ICPP girls following drug withdrawal is usually overestimated and precautions should be taken when this parameter is used.

Objective To study changes in T lymphocyte subsets in preterm infants with intrauterine growth retardation (IUGR). Methods The study enrolled 29 IUGR preterm infants, 38 preterm infants born appropriate for gestational age (AGA), and 20 healthy full-term infants. Peripheral blood was sampled during the first 24 hours of life, and again at a corrected age of 38 weeks of the preterm infants. T lymphocyte subsets were analyzed by flow cytometry, and absolute counts of leukocytes, total lymphocytes, and T lymphocytes were determined with an automated hematology analyzer. Results Within the first 24 hours of life, percentages of CD3⁺ and CD4⁺ were lower in IUGR preterm infants than in AGA preterm infants and full-term infants (P<0.05), percentages of CD8⁺ and CD4⁺/CD8⁺ ratio were lower in IUGR preterm infants than in full-term infants (P<0.05), and percentages of CD3⁺, CD4⁺ and CD4⁺/CD8⁺ ratio were lower in AGA preterm infants than in full-term infants (P<0.05). Moreover, the absolute counts of total lymphocytes were lower in IUGR preterm infants than in full-term infants (P<0.05); the absolute counts of T lymphocytes were lower in preterm infants, regardless of IUGR, than in full-term infants (P<0.05), and lower in IUGR infants than in AGA infants (P<0.05). At the corrected age of 38 weeks, percentages of CD3⁺, CD4⁺ and CD4⁺/CD8⁺ ratio were increased in both IUGR and AGA infants as compared to the measurements within the first 24 hours of life (P<0.05), and percentages of CD3⁺, CD4⁺, CD8⁺ and CD4⁺/CD8⁺ ratio were lower in IUGR infants than in AGA infants (P<0.05), whereas there were no significant differences in counts of leukocytes, total lymphocytes and T lymphocytes between IUGR and AGA infants (P >0.05). Conclusions There may be a certain degree of compromise in cell-mediated immunity in preterm infants with IUGR and this compromise may last to 38 weeks after birth.

Objective This study aimed to evaluate the effectiveness of multi-disciplinary treatment approaches in reducing neurological disabilities in premature infants. Methods A total of 117 infants who were born premature in our hospital between March 2008 and February 2010 but had no congenital malformations and no severe neonatal complications, were enrolled in this study. They were randomly allocated to a multi-disciplinary treatment group (n=63) and a control group (n=54). While patients in the control group underwent an early conventional treatment, those in the multi-disciplinary treatment group were subjected to regular development monitoring, neurological examination and screening for brain injury, neuro-nutrition and neurodevelopment therapies, and rehabilitation training. Results The incidence rates of abnormalities in posture, reflex, sleep, muscle tone and EEG were significantly lower in the multi-disciplinary treatment group than in the control froup (P<0.05) at corrected postnatal ages of 6-12 months. At corrected postnatal ages of 6, 12, 18 and 24 months, both mental development index (MDI) and psychomotor development index (PDI) scores were significantly higher in the multi-disciplinary treatment group than in the control group (P<0.05). At corrected postnatal age of 3 years, incidence rates of cerebral palsy, language barrier, abnormal muscle tone and hearing impairment were significantly lower in the multi-disciplinary treatment group than in the control group (P<0.05). Conclusions Early multi-disciplinary intervention approaches may significantly improve mental and motor developments and reduce the incidence of cerebral palsy-associated neurological disabilities in premature infants.

Objective To define cut-off values of plasma amino-terminal pro-B-type natriuretic peptide (NT-ProBNP) for the diagnosis of congenital heart failure (CHF) and evaluate the importance of plasma NT-ProBNP measurement in the assessment of cardiac function prior to heart surgery in infants with congenital heart disease (CHD). Methods Plasma levels of NT-proBNP were measured in 120 infants with CHD before heart surgery and in 100 age-matched healthy infants between June 2010 and June 2013. The data were stratified based on the presence or absence of CHF in the whole group of CHD infants and on age (i.e., <1 year and ≥1 year) and time (i.e., before surgery) within the subgroup of CHF infants. Results Of the 120 infants with CHD, 41 met the criteria for CHF defined in the Ross Classification for Heart Failure in Infants.The cut-off values of plasma NT-ProBNP were ≥498 ng/L for infants of all ages, 557 ng/L for <1 year age group and 452 ng/L for ≥1 year age group, respectively, in the 41 CHF patients. In CHF infants, plasma NT-proBNP was significantly decreased after protecting of cardiac function (P<0.001). Conclusions The cut-off values of plasma NT-ProBNP for CHF differ between infants <1 year and infants ≥1 year. Moreover, plasma NT-ProBNP can be used as an additional parameter in the preoperative assessment of cardiac function in CHD infants.

Objective To determine serum levels of resistin and visfatin in the patients with acute Kawasaki disease before and after intravenous immune globulin (IVIG) treatment. Methods A total of 50 children with acute Kawasaki disease were treated with IVIG for 48 hours between January 2011 and January 2013. As controls, 30 healthy children and 30 children with acute infectious diseases were included. Serum levels of resistin and visfatin were measured by ELISA both before and after the treatment. Results The baseline serum levels of resistin and visfatin were significantly higher in patients with acute Kawasaki disease than in the two control groups of subjects (i.e., healthy children and patients with acute infectious diseases; P<0.05). In the 50 patients with Kawasaki disease, 38 were not responding and 12 were responding. Serum resistin levels before treatment were significantly higher in non-responders than those in responders (P<0.05). A significant decrease in serum levels of resistin after treatment was observed in IVIG responders (P<0.05). Serum visfatin levels were not significantly different between IVIG responders and non-responders (P >0.05). Additionally, serum resistin and visfatin levels were not significantly different between acute Kawasaki disease patients with and without coronary artery lesions. Conclusions Resistin and visfatin may play important roles in the development of Kawasaki disease and serum resistin may be used as a novel outcome indicator of the IVIG treatment.

Objective To investigate the expression of myeloid-related protein complex (MRP-8/14) in children with acute Kawasaki Disease (KD). Methods A total of 41 children with acute KD and 40 age-and sex-matched control children with upper respiratory tract infection were recruited. Serum levels of MRP-8/MRP-14 complex were measured by ELISA, messenger ribonucleic acid (mRNA) abundance of MRP-8 and MRP-14 in circulating granulocytes and monocytes was determined by RT-PCR, and the number of circulating endothelial cells was determined by flow cytometry. Results When the analysis was stratified according to the presence or absence of coronary artery ectasia in the KD patient group, serum levels of MRP-8/MRP-14 complex, MRP-8 and MRP-14 mRNA abundance in granulocytes, and the number of circulating endothelial cells were all significantly higher in KD patients with coronary artery ectasia than in KD patients without coronary artery ectasia (P<0.05). Serum levels of MRP-8/MRP-14 complex were positively correlated with the number of endothelial cells in the circulation (r=0.69, P<0.05). Conclusions Serum levels of MRP-8/MRP-14 complex are elevated in a positive association with the number of circulating endothelial cells in KD children with coronary artery ectasia, suggesting a causative role in the development of coronary artery lesions.

Objective To analyze the clinical and immunological features of children with lupus nephritis (LN). Methods Chart records of 40 (4 male and 36 female) LN children who were admitted consecutively between January, 2005 and December, 2010 were reviewed. The baseline demographic, pathological and immunological data were analyzed. Results In the 40 LN patients analyzed, the mean age of the disease onset was 10.6±2.6 (range from 2.6 to 14.3) years, and 35 cases (88%) were school-age children. Proteinuria was detected in all 40 cases, including nephrotic-range proteinuria in 12 (30%) cases, and isolated proteinuria in 9 (22%) cases. Twenty-six (65%) patients had varying degrees of hematuria. Acute nephritis was the most common sub-type, accounting for 47% of the total cases. Among the 39 cases undergoing renal biopsy, 3 were unclassified and the remaining 36 were classified, respectively, as type Ⅳ LN (50%, 18 cases), type Ⅱ LN (22%, 8 cases). In the histopathologcally classified case, 100% were antinuclear antibody-positive, 61% were anti-dsDNA-positive, and 89% showed varying degrees of decrease in serum C3 and C4 concentrations. Following treatment for 6 months, a high LN remission rate (95%) was achieved; the acute renal activity index remained higher in Ⅳ, V+Ⅲ and V+Ⅳ subtypes than in other subtypes, while the chronic index and the degree of tubulointerstitial damage were not different between histopathological subtypes. Conclusions The clinical manifestations of LN children are diverse. Clinically, acute nephritis is the most common form of LN in children. Histopathologically, type Ⅳ is the most frequent subtype of LN. Early treatment may result in significant disease remission.

Objective To retrospectively assess serious systemic adverse effects of standardized dust-mite vaccine in children with asthma. Methods Medical records of 704 children (5-17 years in age) with asthma between January, 2005 and December, 2011 were reviewed. Serious systemic adverse events following treatment with a standardized dust-mite vaccine in these children were analyzed. Results A total of 336 systemic adverse reactions were observed in 17.0% (120/704) of the patients analyzed of these adverse reactions, 18 (5.4%) were serious (level 3), 318 (94.6%) were not serious (below level 3), and no single case of anaphylactic shock (level 4) was recorded. Systemic adverse events occurred most frequently in the 5 to 11-year age group and in the summer season (from June to August). In the 18 severe cases, the peak expiratory flow (PEF) dropped by 20% immediately after the vaccine injection, and other major clinical symptoms included cough, wheezing and urticaria. All children with serious systemic adverse effects were given inhaled hormone and atomized short-acting beta agonists, oral antihistamines, intravenous dexamethasone and/or intramuscular adrenaline. After these treatments, the clinical symptoms were significantly relieved. Conclusions The rate of serious systemic adverse events following allergen-specific immunotherapy is relatively low in children with allergic asthma. Conventional medications are effective in managing these immunotherapy-associated adverse events.

Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive disorder. It is known that MTHFR deficiency may result in hyperhomocysteinemia, but MTHFR deficiency-induced schizophrenia has been rarely reported. Here we present the clinical course, biochemical and genetic characteristics of schizophrenia resulted from MTHFR deficiency in a school-age boy. He was 13 years old. He was admitted with a two-year history of fear, auditory hallucination, learning difficulty, sleeping problems, irascibility, drowsing and giggling. At admission, he had significantly elevated plasma and urine levels of total homocysteine, significantly decreased levels of folate in serum and cerebrospinal fluid, and a normal blood concentration of methionine. Further DNA sequencing analysis showed 665C>T homozygous mutations in the MTHFR gene. The patient was diagnosed with MTHFR deficiency-associated schizophrenia and treatment with calcium folinate, vitamin B₁₂, vitamin B₆, and betaine was initiated. After the treatment for 1 week, his plasma and urine levels of homocysteine were decreased to a normal range and the clinical symptoms were significantly improved. After 3 months of treatment, the patient returned to school. He is now living with normal school life. In summary, children with late-onset MTHFR deficiency and secondary cerebral folate deficiency may lead to schizophrenia. This rare condition can be early diagnosed through analyses of blood and urine total homocysteine, amino acids in blood and folate in blood and cerebral fluid and successfully treated with folinic acid, vitamin B₆, vitamin B₁₂ and betaine.

Objective To study changes in paired-immunoglobulin-like receptor B (PirB) expression after hypoxic-ischemic brain damage (HIBD) as well as the role for targeted inhibition of PirB activity in nerve regeneration in rats. Methods Newborn Sprague-Dawleyrats rats were divided into: a sham operation group (n=30), a HIBD group (n=30), and an anti PirB antibody treatment group (n=6). In the HIBD group, HIBD was induced by right carotid artery ligature and subsequent exposure to hypoxia (8% O₂) for 3 hours. In the sham operation group, right carotid artery was dissected as in the HIBD group but no ligature and hypoxic exposure was not applied. In the two groups, 6 animals were sacrificed at 0, 6, 12, 24 and 72 hours after the operation and hypoxic exposure. In the antibody treatment group, after carotid artery ligation and hypoxia exposure as in the HIBD group, an anti PirB antibody was injected intracerebrally and animals were sacrificed 72 hours after the injection. Immediately after sacrifice of the animals at designated time points, brain tissue specimens were collected. The presence and content of PirB protein were assessed by immunohistochemistry and Western blot analysis respectively, the abundance of PirB mRNA was determined by RT-PCR, and the Rho kinase (Rock) activity was determined by immunoprecipitation. Results At 72 hours after operation, PirB mRNA abundance and protein content in the brain were significantly increased as compared with the measurements at 0 hour after operation in the HIBD group (P<0.05); ROCK activity was significantly increased in the HIBD group as compared with the sham operation and anti PirB antibody groups (P<0.05). Conclusions PirB might be involved in HIBD through a Rho-ROCK-dependent mechanism and antibody-mediated neutralization of PirB in the brain may offer a novel therapeutic strategy for HIBD.

Objective To study the effect of β₈ expression on transforming growth factor β1(TGF-β1) activation in astrocytes with oxygen glucose deprivation (OGD). Methods Astrocytes were cultured and then subjected to OGD to generate hypoxia-ischemia (HI) model in vitro. Immunocytochemistry was used to detect the expression and distribution of β₈ in nomoxia cultured cells. β₈ protein expression was quantified by Western blot at 12 hours, 1 day and 2 days after OGD. Astrocytes and luciferase reporter cells (TMLC) were co-cultured. β₈ RNA interference system was established to specifically inhibit β₈ expression in cultured astrocytes. TGF-β1 activation was then detected in the co-culture system. Results β₈ was mainly located in the cytoplasm and neurites of astrocytes. OGD resulted in increase of β₈ protein expression at 12 hours after reoxygenation in astrocytes, which was peaked at 1 day after reoxygenation. TGF-β1 activation was in accordance with β₈ expression in astrocyte-TMLC co-culture system after reoxygenation. After the inhibition of β₈, TGF-β1 activation was significantly reduced in all time points. Conclusions The highly expressed β₈ plays important roles in the regulation of TGF-β1 activation in neonatal rats with hypoxic-ischemic brain damage.

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Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by non-cardiogenic, acute and progressive respiratory failure mediated by a variety of injurious stimuli. ALI can progress to ARDS if an effective management is not taken. The mortality rate remains high due to the complex pathogenesis and ineffective management of ARDS. At present, effective treatment methods for ALI are not available and thus it is important to study the pathogenesis and early diagnosis of ALI. This article reviews some of the biomarkers associated with ALI, with a focus on early diagnosis and future studies.

Steroid-resistant nephrotic syndrome poses a significant clinical challenge. Its pathogenesis has not been fully elucidated. In recent years, numerous studies have shown that podocyte-specific gene mutations may play important roles in the development of steroid-resistant nephrotic syndrome. Among the identified genes mutated in podocytes include NPHS2, NPHS1, WT1, TRPC6, MDR1, PLCE1, LMX1B, and LAMB2. This review aims to summarize the characteristics of these mutated genes in podocytes. The putative role for these podocyte-specific mutated genes in the pathogenesis, diagnosis, treatment and prognosis of steroid-resistant nephrotic syndrome is also discussed.