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Special Topic and Discussion

Original Papers

  • Effect of zinc supplementation on mental development and motor development in infants: a meta-analysis
  • ZHU Di-ling, MAO Meng, YANG Wen-xu, YANG Hui-min
  • 2011 Vol. 6 (1): 4-10. DOI:
  • Abstract ( 4329 ) PDF (7932KB)( 3939 )
  • Objective To assess the efficacy of zinc supplementation for improving psychomotor developmental and mental developmental outcomes in infants younger than 3 years. Methods According to the requirements of Cochrane systematic review, a literature search was performed among PubMed, EMBASE, Cochrane library, CNKI, VIP and Wanfang data from the establishment of the database till October 2010. Mental developmental index (MDI), psychomotor developmental index (PDI) and development quotient (DQ) of 6-36 months after birth were measured as therapeutic efficacy index.RevMan 5.0 software was used for metaanalysis. The Cochrane handbook 5.0.2 was used to evaluate the methodological quality. Data extraction, quality assessment, and metaanalysis for the results of homogeneous studies were performed by two reviewers. Heterogeneity of the included articles was tested to select proper effective model. Measurement data were expressed as SMD, WMD and its 95%CI. Results Eightyfour articles were searched according to the inclusion and exclusion criteria, 21 reviews, 37 studies without zinc supplementation, 5 studies for pregnant mothers, 5 studies for children older than 3 years, 1 study in which zinc supplementation was not the only different intervention compared with control group and 5 studies without the outcomes were excluded. Ten RCTs meeting the inclusion criteria were enrolled. The assessment of literature quality showed 7 literatures described the method of random allocation in detail,8 literatures described allocation concealment, 8 literatures used double blind method,9 literatures reported complete data addressed and 9 literatures were free of selectively reporting. Only 1 literature described the sources of other bias.There was clinical heterogeneity in the 10 included studies. Nine RCTs (n=2 250) reported PDI with the Bayley Scales of Infant Development or Griffiths Mental Development Scales. There was no significant difference in the PDI between two groups, SMD=0.15(95%CI:-0.12 to 0.42). Eight RCTs (n=2 136) reported MDI with the Bayley Scales of Infant Development. There was no significant difference in the MDI between two groups, WMD=-0.08(95%CI:-1.55 to 1.40). Subgroup analyses were carried out for dosage, formulation (zinc alone or zinc combined with other nutrients) and nutrition status (varying measles case fatality rates). None of these subgroup analyses showed significant difference in the MDI or PDI between groups. One RCT (n=114) reported DQ using the Griffiths Mental Development Scales. The WMD of DQ was -0.72 (95%CI:-7.97 to 6.53). Another RCT (n=70) reported the change in Alberta Infant Motor Scale and did not show significant difference between groups, WMD=0.30(95%CI:-2.09 to 2.69). Conclusions Supplementation of zinc shows no effect on psychomotor development and mental development in infants. Further studies are needed to determine whether the findings are reproducible.

  • Meta-analysis of cyclophosphamide treating proliferative lupus nephritis
  • SHEN Qi,YANG Tong,HUANG Xian-wen,OU YANG Xiao-lin,GONG Xin-fang,HUANG-Jing
  • 2011 Vol. 6 (1): 11-22. DOI:
  • Abstract ( 3316 ) PDF (12512KB)( 4817 )
  • Objective To assess the effective and safety of Cyclophosphamide in the treatment of Proliferative Lupus Nephritis. Methods We search The Cochrane library 、PUBMED 、EMBASE 、CBMdisc 、CNKI 、VIP to 30 June 2009. Results Twenty-nine studies involving 1900 participants were included。 Meta-analysis showed:① High dose CTX Compared with Low dose CTX,The Doubling of serum creatinine have statistically significant, ② CTX plus steroids Compared with steroids alone,The ESRD、Doubling of serum creatinine and Relapse have statistically significant, The CTX plus steroids are less than control groups;And Stable renal function、Herpes zoster infection and Ovarian failure have statistically significant。 ③ CTX plus steroids Compared with MMFplus steroids,The Complete remission and Total remission have statistically significant;And Amenorrhoea and Leucopenia have statistically significant④ CTX plus AZA Compared with MMF,The Amenorrhoea and Leucopenia have statistically significant。Conclusion Available evidence show:Compared with steroids alone, The effect of CTX plus steroids is better than steroids alone;Compared with MMF plus steroids, The effect of CTX plus steroids is less than MMFplus steroids,and the side effect is higher than MMFplus steroids;Compared with MMF, The effect of CTX plus AZA was similar,but the side effect is higher than MMF;The smallest effective dose and shortest duration of treatment should be used to minimise gonadal toxicity,without compromising efficacy.

  • Sequence analyses for full length genomes of human enterovirus 71 strains isolated from children in Beijing from 2008 to 2009
  • ZHANG Hui-juan, ZHU Ru-nan, QIAN Yuan, DENG Jie, ZHAO Lin-qing, WANG Fang, DENG Li, ZHANG Yan-ling
  • 2011 Vol. 6 (1): 23-30. DOI:
  • Abstract ( 2965 ) PDF (12199KB)( 3276 )
  • Objective To investigate whether the variation of the pathogenicity of enterovirus71(EV71) was related to the variation of the nucleotide sequencing of the virus of the full length genomes of EV71 strains isolated from pediatric patients with hand, foot and mouth disease (HFMD) presenting different symptoms in Beijing from 2008 to 2009. Methods Five EV71 strains in 2008 and 4 EV71 strains in 2009 isolated from Laboratory of Virology of Capital Institute of Pediatrics were chosen, of which 4 EV71 strains were isolated from severe HFMD children with high fever, continuous convulsion and loss of consciousness. Five EV71 strains were isolated from mild HFMD children.The full length genomes from 9 EV71 strains isolated from children with various clinical presentations were sequenced by amplification with RT-PCR and sequencing of 10 overlapped gene fragments covering full length of the genomes. Their nucleotide and amino acid sequences were aligned and phylogenetic relations of the sequences were analyzed by using DNAStar and MEGA software (version 4.1). Results The full length of 9 EV71 strains isolated from children in Beijing from 2008 to 2009 was 7 405 bp or 7 406 bp (Poly A tail not included) with a deletion in the 5′UTR for 6 out of these 9 strains. The overall nucleotide sequence identities of these 9 EV71 isolates were in the range of 96.3%-99.4%, while amino acid sequence identities were 98.2%-99.6%. The homology of the nucleotide sequences of VP1 of these 9 EV71 isolates was 96.9%-99.9%, while the homology of the amino acid sequences was 98.3%-100.0%. The majority of nucleotide changes were located at the third codon positions which caused silent mutations, thus the deduced amino acid sequence changes among those 9 EV71 isolates were scanty. The residue 144 in the VP2 protein and the residues 140 and 263 in the 3D polymerase (3Dpol) which were T, R and I were substituted by S, K and V, respectively in 3 out of 4 neurovirulent strains. Two bases, G and A at the nucleotides 208 and 254 in the 5′UTR were substituted respectively by A and G in the same 3 of those 4 neurovirulent strains. The nucleotide sequences of 9 EV71 isolates in the 5′UTR, P1, P2, P3 and 3′UTR regions exhibited the highest homology to the subgenotype C4 of EV71. However, when compared with CVA16 prototype strain G10, the nucleotide identities within the 3D and 3′UTR regions were higher than those of known genotypes A, B, C1-C3 and C5 of EV71. These 9 EV71 isolates formed a branch with other EV71 isolates circulating in mainland China and Taiwan previously identified as genotype C4 on the two phylogenetic trees. Conclusions The data from this study suggests that mutations at the residue 144 in the VP2 protein (T→S), the residues 140 and 263 in the 3Dpol (R→K and I→V) and the nucleotide 254 in the 5′UTR (A→G) may be associated with the severity of clinical presentations. Based on the entire VP1 gene sequences, the EV71 viruses circulating in Beijing from 2008 to 2009 should be classified as the subgenotype C4. The nonstructural protein encoding genomic regions may play a role in the evolution of EV71.

  • The analysis of relationship between creatine kinase, troponin Ⅰ and the prognosis in critically ill children with sepsis
  • HUANG Jiao-tian, ZHU Yi-min, LU Xiu-lan
  • 2011 Vol. 6 (1): 31-36. DOI:
  • Abstract ( 2951 ) PDF (4966KB)( 3662 )
  • Objective To investigate the incidence of myocardial injury in the critically ill septic childern,and the relationship between elevations of serum troponin Ⅰ (cTnⅠ), creatine kinase (CKMB) and the prognosis outcomes, including the incidence of myocardial injury ,mortality, acute physiology and chronic health Ⅱ (APACHE Ⅱ) score. To evaluate the significance of elevations of cTnⅠ, CKMB and APACHE Ⅱ in critically ill children with sepsis. Methods Children with severe sepsis hospitalized in ICU of Hunan Provincial Children′s Hospital from August 2009 to May 2010 were retrospectively collected as sepsis group and chidren without sepsis were chosen as control group. The levels of troponin Ⅰ, creatine kinase and APACHE Ⅱ score, myocardial injury, mortality and quality of life were measured. The levels of troponin Ⅰ, creatine kinase concentration and the duration were compared. Results Totally 656 children were enrolled into the study, including 459 in sepsis group(352 boys and 107 girls) and 197 in nonsepsis group(151 boys and 46 girls). Two hundred and five (44.7%) of the 459 critically ill children with sepsis showed elevated levels of cTnⅠ or/and CKMB.The levels of cTnⅠ, CKMB and APACHE Ⅱ score were positively correllated. Serum CKMB,cTnⅠ and APACHE Ⅱ scores were independent risk factors for predicting mortality of septic patients.The levels of CKMB and cTnⅠ in death group were significantly higher than in survival group. The levels of CKMB and cTnⅠ in high APACHE Ⅱscores(≥25) group were significantly higher than in low APACHE Ⅱ scores(<25)group.The patients with high APACHE Ⅱ scores and high serum CKMB,cTnⅠ levels had shorter survival time. Conclusions The incidence of myocardial injury defined by elevated levels of cTnⅠ and CKMB is unexpectedly high and is associated with mortality. Continuous monitoring of serum cTnⅠ, CKMB concentration and APACHE Ⅱ score of children with sepsis, not only help to assess the condition of children, but also predict the prognosis of them.

  • Association between Polymorphism of Surfactant Protein B Gene and Neonatal Respiratory Distress Syndrome.
  • ZENG Ling-kong, LI Wen-bing, PAN Rui, SHAN Rui-yan, ZHOU Yu-rong, ZHANG Jia, CHANG Li-wen
  • 2011 Vol. 6 (1): 37-41. DOI:
  • Abstract ( 3140 ) PDF (1004KB)( 3922 )
  • Objective To study the relationship between gene polymorphisms of surfactant protein B (SPB) and neonatal respiratory distress symdrome susceptibility. Methods Children diagnosed as neonatal respiratory distress syndrome(NRDS ) from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were enrolled. The children born at the same gestation age were taken as control group and the ratio of NRDS group to control group was 1∶2. Genomic DNA was extracted from peripheral blood by EDTA anticoagulation,using a standard Phenol/chloroform extraction procedure. The genetic polymorphisms of SPB18A/C and SPB1580C/T were analyzed with polymerase chain reaction restriction fragment length polymorphism(PCR-RFLP) using the restriction enzyme Apapl and DdeⅠ. Statistical analyses were carried out using SPSS software version 13.0. The Hardyweinberg equilibrium was determined for both NRDS and control groups. χ2 test was used to detect the difference between two groups. Results Ninety one children with NDRS were chosen as NRDS group and 182 children were enrolled as control group from 2008 to 2010. ①The SPB18 AA, AC, and CC genotype frequencies in NRDS group were 11.0%, 40.7%, 48.4% versus 6.6%, 31.3%, and 62.1% in control group, both were with no significant difference(P>0.05). The frequencies of A allele were higher in NRDS group than those in control group(22.3% vs 31.3%). ②The SPB1580 TT, TC, and CC genotype frequencies in NRDS group were 5.5%, 63.7%, 45.1% versus 30.8%, 6.6%, and 48.4% in control group, both were with no significant difference(P>0.05). The frequencies of C allele were higher in NRDS group than those in control group(79.1% vs 70.9%). ③ The genotype frequencies of 1580 C among Han and American, Brazilian, Dane were 79%, 35%, 41% and 46%(P<0.05) and 72% in Japanese(P>0.05). The Genotype frequencies of -18A among Han and American, Brazilian, Dane were 31%, 58%, 57% and 61%(P<0.05). Conclusions The genetic polymorphisms of SPB-18A/C and SPB1580C/T were the independent risk factors of neonatal respiratory distress syndrome. The polymorphisms of SPB-18A/C and 1580C/T differ among races.

  • Study on the relationship between human milk neutral oligosaccharides and FUT2 gene polymorphism
  • ZHANG Zhuo-jun, ZHANG Lei, YAO Wen, WANG Yan-yan, Ardythe Morrow, PENG Yong-mei
  • 2011 Vol. 6 (1): 42-47. DOI:
  • Abstract ( 2501 ) PDF (1899KB)( 2892 )
  • Objective To investigate the concentration of human milk neutral oligosaccharides 2 weeks after birth and genetic sequence variation in gene FUT2. Oligosaccharides concentration was analyzed based on SNPs to explore the relationship between oligosaccharides differences and gene polymorphisms. Methods Term infants and their mothers who planned to give the infants at least 75% breast milk in 3 months after delivery were included. Breast milk and saliva sample were collected at 2 week postpartum. Neutral oligosaccharides concentration of breast milk was analyzed by high performance liquid chromatography. Saliva sample was collected using Oragene Kit. DNA was extracted from saliva sample and used for SNP assay. Results One hundred and ten breastfeeding motherinfant pairs in Shanghai were recruited in this study, of them 78 mothers were taken human milk neutral oligosaccharides detection. According to the classification of the neutral oligosaccharides, Le(a-,b-) accounted for 21.8%; Le(a-,b+) accounted for 51.3% and Le(a+,b-) accounted for 26.9% in breast milk. There were three genotypes of SNP (rs1047781) i.e. AA, AT and TT (26.7%, 48.6% and 24.8% respectively). Sixty mothers were taken the detection of human milk neutral oligosaccharides and SNP rs1047781 polymorphisms. The concentration of ɑ1,2 linked oligosaccharides was significantly different among the three groups. Conclusions The distribution of Lewis phenotype according to the classification of the neutral oligosaccharides matches with the distribution of general population in China. It is the important regulating spot of ɑ1,2 linked oligosaccharides concentration in Chinese mothers′ breast milk.

  • Differences in fecal calprotectin levels of six-month-old infants in poor rural and affluent urban areas in China and its determinants
  • LIU Jin-rong, SHENG Xiao-yang, HU Yan-qi, YU Xiao-gang, LIU Shan-shan, ZHANG Jie
  • 2011 Vol. 6 (1): 48-53. DOI:
  • Abstract ( 3017 ) PDF (1137KB)( 3024 )
  • Objective To compare fecal calprotectin(FC)levels in poor rural and affluent urban infants, to evaluate the impact of breastfeeding and complementary feeding on FC levels. Methods From October 2009 to June 2010, the feces were obtained from poor rural infants in Yunnan and affluent urban infants in Shanghai. The samples were examined with an ELISA kit. The breastfeeding and complementary feeding information of infants was collected. FC levels in infants were compared between the two areas, the impact of breastfeeding and complementary feeding on FC levels was analyzed. Results 145 infants were involved in the study, 10 infants missed part of information, finally 135 infants were enrolled into the study, of them 96 infants were from poor rural area, 39 infants were from affluent urban area. FC levels were beyond the test range (>600 μg·g-1) in 36 infants. The rate in poor rural infants (34 infants, 35.4%) was significantly higher than that in affluent urban infants (2 infants, 5.1%) (P<0.01). In other 99 infants whose FC levels were less than 600 μg·g-1, the median level was 172.0 μg·g-1 (24.5-595.9 μg·g-1), which was significantly higher than the cutoff level in adults (<50 μg·g-1). There was no difference between boys and girls. In affluent urban infants, FC levels were beyond the test range in 2 infants. The median FC level in other 37 infants was 138.8 μg·g-1(26.2-557.2 μg·g-1). But in poor rural infants, FC levels were beyond the test range in 34 infants. The median FC level in other 62 infants was 196.4 μg·g-1(24.5-595.9 μg·g-1), which was significantly higher than that in affluent urban infants (P<0.05). Breastfeeding and complementary feeding had no impact on FC levels. Weight gain in the first six months in affluent urban infants was significantly higher than that in poor rural infants, (5.0±0.9) kg vs (4.3±0.9) kg,P<0.01. Conclusions FC levels in sixmonthold infants are much higher than the cutoff level in adults. FC levels are higher in sixmonthold infants in poor rural area than those in affluent urban area, especially, FC levels are beyond the test range in 35.4% infants in poor rural area. It is warranted to further study if the high FC levels imply mild gut inflammation or the immunostimulation impacts the infant growth.

Methology in Evidence-based Medicine

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