Association of variants of ABCB11 with transient neonatal cholestasis.

BACKGROUND: The significance of ABCB11 variants have been studied in some cholestatic diseases, but this is not clear in transient neonatal cholestasis (TNC). The aim of the present study was to explore the association between ABCB11 variants and TNC. METHODS: This was a case-control study. A total of 192 children with TNC referred to a tertiary referral hospital in eastern China were enrolled as subjects, and 196 healthy children were selected as controls. Part of the promoter and exons of the ABCB11 gene were sequenced directly. The single nucleotide polymorphism (SNP) site of V444A was tested using fluorescent quantitative polymerase chain reaction. Potential consequences of variants were predicted using bioinformatics software. The biochemistry indices were compared between the patients with or without possibly pathogenic variants/mutations. RESULTS: Twenty-eight variants, including 14 novel ones, were detected. Four novel, possibly pathogenic mutations (I416I, K436N, R928Q and IVS7+5G>A) were detected in six subjects. The γ-glutamyltransferase level of these six was lower than in the others (P = 0.054). The genotype distribution of the four common SNP sites, V444A, A535A, A865V and A1082A, was not significantly different between TNC patients and controls. CONCLUSIONS: Approximately 3% of TNC cases can be attributed to ABCB11 mutations.

[Characteristics of the plasma amino acid spectrum of neonatal intrahepatic cholestasis caused by citrin deficiency].

OBJECTIVE: To investigate the plasma amino acid spectrum in infants more than 1-year-old with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in order to identify potential diagnostic markers of NICCD. METHODS: Infants less than 1 year of age who had been referred to our hospital for investigation of suspected conjugated hyperbilirubinemia between June 2003 and June 2009 were eligible for enrollment. A total of 182 infants were enrolled and divided into three groups: infants diagnosed with NICCD (n = 24), according to gene testing and/or western blotting results; infants diagnosed with biliary atresia (BA; n = 20), according to intra-operative cholangiography findings; and infants diagnosed with idiopathic neonatal intrahepatic hepatitis (INH; n = 138), according to exclusionary findings for diseases affecting the extrahepatic biliary system and no positive serology results to indicate infections with hepatitis B, C, A or E, toxoplasmosis, rubella, herpes simplex, human immunodeficiency virus-1, or syphilis. The plasma amino acid spectrum of each infant was analyzed by tandem mass spectrometry (MS/MS). The concentrations of 18 amino acids, as well as the ratio of each amino acid to total amino acids, were compared among the three groups. Selected ratios of amino acids were analyzed by receiver operating characteristic (ROC) curve analysis. RESULTS: Compared with the BA and INH groups, the NICCD group had significantly lower levels of alanine (Ala; 175.7 and 205.7 vs. 136.3 mumol/L, P = 0.0001), aspartic acid (Asp; 47.5 and 43.1 vs. 31.55 mumol/L, P = 0.0041), glutamic acid (Glu; 276.16 and 263.24 vs. 175.71 mumol/L, P = 0.0075) and tryptophan (Trp; 41.90 and 47.97 vs. 28.51 mumol/L, P = 0.0003), but significantly higher levels of methionine (Met; 28.24 and 29.35 vs. 71.40 mumol/L, P = 0.0390), tyrosine (Tyr; 55.8 and 57.02 vs. 116.81 mumol/L, P = 0.0072) and citrulline (Cit; 15.09 and 15.65 vs. 97.42 mumol/L, P = 0.0001). The ratio of each amino acid to total amino acids showed the same trends for the NICCD group. The calculated areas under the ROC curves of the ratios of Cit, Tyr, and Met to the total amino acids were 0.874 (95% CI: 0.752 - 0.996), 0.814 (95% CI: 0.706 - 0.923), and 0.705 (95% CI: 0.535 - 0.875) respectively. The calculated area under the ROC curve of the ratio of Cit to Ala was 0.893 (95% CI: 0.781 - 1.005), and when the cut-off value of the ratio of Cit to Ala was 0.14 for diagnosis of NICCD, the sensitivity and specificity were 75% and 95% respectively. CONCLUSION: The plasma amino acid spectrum may represent a diagnostic indicator for NICCD, particularly the ratio of Cit to Ala.

ABCB11 gene mutations in Chinese children with progressive intrahepatic cholestasis and low gamma glutamyltransferase.

BACKGROUND: Progressive familial intrahepatic cholestasis type 2 (PFIC2) is a severe autosomal recessive liver disorder of childhood that can cause cholestasis and progress to end-stage liver disease. ABCB11 gene mutations causing PFIC2 have been reported in some population groups, but not in mainland Chinese. AIMS: To elucidate the existence of and characterize ABCB11 gene mutations in mainland Chinese with progressive intrahepatic cholestasis and low gamma glutamyltransferase (GGT). METHODS: Twenty-four children presenting with progressive intrahepatic cholestasis and low GGT were admitted to a tertiary paediatric hospital in eastern China from January 2004 to July 2007. All encoding exons and flanking areas of the ABCB11 gene were sequenced. Hepatic histopathology results were obtained by review of the medical record. RESULTS: Twelve novel mutations of ABCB11 gene were found in seven patients: three nonsense mutations, six missense mutations, two splicing mutations and one intronic mutation. Giant cell transformation of hepatocytes was demonstrated in all the four patients with ABCB11 mutations and four of 12 patients without mutations in coding sequences of ABCB11 gene who received liver needle biopsy. CONCLUSIONS: ABCB11 gene mutations play an important role in Chinese patients with progressive intrahepatic cholestasis and low GGT. The characteristics of ABCB11 gene mutations in Chinese are different from other population groups. Histological examination may be helpful in diagnosis of PFIC2.

Characterization of ATP8B1 gene mutations and a hot-linked mutation found in Chinese children with progressive intrahepatic cholestasis and low GGT.

OBJECTIVES: The aim of the study was to elucidate the role and characteristics of ATP8B1 gene mutations in mainland Chinese children with progressive intrahepatic cholestasis and low gamma-glutamyltransferase (GGT). PATIENTS AND METHODS: Twenty-four children who presented with progressive intrahepatic cholestasis and low GGT were admitted to a tertiary pediatric hospital in eastern China from January 2004 to July 2007. Five children with homozygous or compound heterozygous ABCB11 gene mutations were excluded from the study. All encoding exons and their flanking areas of ATP8B1 gene were sequenced in the remaining 19 patients, in whom only 1 or no mutation of ABCB11 was found. Clinical features and liver histology obtained by reviewing the medical records were compared among patients with different genotypes. RESULTS: Nine mutations of ATP8B1 gene were found in 9 patients. All of them were novel except for mutations I694N and R952X. A linked P209T and IVS6+5G>T mutation was found in 4 of 9 patients, including 2 homozygotes and 2 heterozygotes. Giant cell transformation of hepatocytes was demonstrated in 1 of 6 patients with ATP8B1 mutations and 4 of 5 patients with ABCB11 mutations. CONCLUSIONS: ATP8B1 gene mutations play an important role in Chinese patients with progressive intrahepatic cholestasis and low GGT. The linked mutation P209T and IVS6+5G>T is a hot mutation in the Chinese population. Histological examination may be helpful in differentiating familial intrahepatic cholestasis type 1 from bile salt export pump-related disease.

[Expression of insulin receptor substrate-2 and its tyrosine phosphorylation in the hepatic tissue of chronic hepatitis B patients].

OBJECTIVE: To observe the expression of insulin receptor substrate-2 (IRS-2) mRNA and protein, and its tyrosine phosphorylation in hepatic tissue of chronic hepatitis B (CHB) patients, and to explore the role of IRS-2 on insulin resistance in CHB patients. METHODS: Eighteen patients with CHB were included, and 6 individuals with normal liver function were enrolled as control. Based on the insulin resistance index determined by homeostasis model assessment (HOMA), CHB patients were further divided into CHB without insulin resistance group (<2.69, n=10) and CHB with insulin resistance group (>2.69, n=8). Hepatic tissues were harvested from all patients during operation or with liver biopsy. The mRNA expression of IRS-2 in liver tissue was assessed by reverse transcription-polymerase chain reaction (RT-PCR), and the protein expression of IRS-2 was detected by Western blotting. Immunoprecipitation and enhanced chemiluminescent technique were used to measure the tyrosine phosphorylation of IRS-2. RESULTS: In CHB without insulin resistance group, the mRNA expression (0.38+/-0.06), the protein expression (0.94+/-0.18) and the tyrosine phosphorylation (0.78+/-0.09) of IRS-2 in hepatic tissue were decreased, but without statistically significant difference (all P>0.05), as compared to those in control group (0.45+/-0.11, 0.99+/-0.20, 1.00+/-0.23, respectively). In CHB with insulin resistance group, the mRNA expression (0.26+/-0.08), the protein expression (0.67+/-0.11) and the tyrosine phosphorylation (0.63+/-0.14) of IRS-2 in hepatic tissue were significantly decreased compared with those of the control group with statistically significant difference (P<0.05 or P<0.01). CONCLUSION: The decreased expression of mRNA and protein and the reduced tyrosine phosphorylation of IRS-2 in CHB patients with insulin resistance inducing impairment of the insulin signal pathway may be one of the mechanisms underlying insulin resistance.

[SLC25A13 gene mutations in Chinese infants with intrahepatic cholestasis and abnormal blood amino acids].

OBJECTIVE: To explore whether SLC25A13 gene mutation exists and what is its mutation spectrum in mainland Chinese infants with intrahepatic cholestasis and abnormal blood amino acids. METHODS: Blood amino acids were analyzed by mass chromatographic analysis in infants referred to Fudan University Children's Hospital from June 2003 to June 2007 for investigations of intrahepatic cholestasis of unknown origin. SLC25A13 gene mutations were studied in 14 children whose serum levels of citrulline and/or methionine were at least two times above the upper normal range. In patients in whom only one mutation was detected, all other exons and their neighboring sequences were then analyzed. RESULTS: Eight patients with SLC25A13 gene mutations, including 2 with compound heterozygous mutation 851del4/1638ins23, one with homozygous mutation 851del4/851del4, one with compound heterozygous mutation 851del4/R184X, one with homozygous mutation IVS6+1G more than A/IVS6+1G more than A, and 3 with heterozygous mutation 851del4 were found. CONCLUSIONS: SLC25A13 gene mutations exist in Chinese infants with intrahepatic cholestasis and abnormal blood amino acids. Their mutation spectrum is different from that in Japan. 851del4 is the most common mutation in our study. IVS6+1G more than A is a mutation that has not been reported before.

Auricular acupressure is an alternative in treating constipation in leukemia patients undergoing chemotherapy: A systematic review and meta-analysis.

OBJECTIVE: Auricular acupressure (AA) therapy has been widely used in Eastern Asia and Europe to prevent constipation in leukemia patients undergoing chemotherapy. The aim of this systematic review was to review data from randomized controlled trials (RCTs) of auricular acupressure therapy for preventing constipation in leukemia patients undergoing chemotherapy. METHODS: Databases that were searched from their inception until August 2017 included: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, as well as four Chinese databases [Chinese BioMedical Database, China National Knowledge Infrastructure, Wan-Fang Data, and the Chinese WeiPu Database]. In this systematic review, only RCTs that were related to the effects of auricular acupressure therapy on preventing constipation in leukemia patients undergoing chemotherapy were included. Study selection, data extraction, and validation were performed independently by two reviewers. Quantitative analyses of RCTs were performed using RevMan 5.3 software, and cochrane criteria for risk-of-bias were used to assess the methodological quality of the trials. RESULTS: A total of 5 RCTs met the inclusion criteria, and most were of low methodological quality. Participants in the AA plus routine care group showed significantly greater improvements in the Bristol Stool Form (BSF) [MD = 0.55, 95% CI (0.39, 0.71), p < 0.01] with low heterogeneity (Chi2 = 5.01, p = 0.29, I2 = 20%). Moreover, when compared with routine care alone, meta-analysis of three RCTs indicated favorable statistically significant effects of AA plus routine care on the Constipation Assessment Scale (CAS) [MD = -1.51, 95% CI (-1.89, -1.14), p < 0.01] with low heterogeneity (Chi2 = 1.63, p = 0.44, I2 = 0%). Furthermore, when compared with routine care alone, meta-analysis of two RCTs demonstrated statistically significant effects of AA plus routine care on the Patient Assessment of Constipation-Quality Of Life (PAC-QOL) [MD = -1.28, 95% CI (-1.44, -1.13), p < 0.01], with low heterogeneity (Chi2 = 0.19, p = 0.67, I2 = 0%). CONCLUSION: Taken together, as a potential safety therapy, only weak evidence supported the hypothesis that AA effectively prevented constipation in leukemia patients undergoing chemotherapy.

Chinese clinical practice guidelines for acute infectious diarrhea in children.

BACKGROUND: The guidelines addressed the evidence-based indications for the management of children with acute infectious diarrhea in Chinese pediatric population. DATA SOURCES: The experts group of evidence development put forward clinical problems, collects evidence, forms preliminary recommendations, and then uses open-ended discussions to form recommendations. The literature review was done for developing this guideline in databases including PubMed, Cochrane, EMBASE, China Biomedical Database, and Chinese Journal Full-text Database up to June 2013. Search the topic "acute diarrhea" or "enteritis" and "adolescent" or "child" or "Pediatric patient" or "Baby" or "Infant". RESULTS: For the treatment of mild, moderate dehydration, hypotonic oral rehydration solutions (ORS) are strongly recommended. Intravenous (IV) rehydration is recommended for severe dehydration, with a mixture of alkali-containing dextrose sodium solution. Nasogastric feeding tube rehydration is used for children with severe dehydration without IV infusion conditions with ORS solution. Regular feeding should resume as soon as possible after oral rehydration or IV rehydration. The lactose-free diet can shorten the diarrhea duration. Zinc supplements are recommended in children with acute infectious diarrhea. Saccharomyces boulardii and Lactobacillus Rhamnus are recommended to be used in acute watery diarrhea. Saccharomyces boulardii is recommended in children with antibiotic-associated diarrhea as well. Montmorillonite and Racecadotril (acetorphan) can improve the symptoms of diarrhea or shorten the course of acute watery diarrhea. Antibiotics are recommended with dysenteric-like diarrhea, suspected cholera with severe dehydration, immunodeficiency, and premature delivery children with chronic underlying disease; otherwise, antibiotics are not recommended. CONCLUSION: The principles of the most controversial treatments with of acute infectious disease are reaching to a consensus in China.

Relationship between IFN-gamma gene polymorphism and susceptibility to intrauterine HBV infection.

AIM: To explore the susceptibility of children to intrauterine HBV infection by studying the relationship between IFN-gamma gene polymorphism, including IFN-gamma+874A/T single nucleotide polymorphism (SNP) and CA repeat microsatellite polymorphism and intrauterine HBV infection. METHODS: A TaqMan fluorescence polymerase chain reaction in the IFN-gamma+874A/T single nucleotide polymorphism was tested in the intrauterine HBV infection group (group I) and the normal immune children group (group II). Capillary electrophoresis was performed in the above two groups to assay the IFN-gamma CA repeat microsatellite polymorphism. RESULTS: Frequencies of AA, AT and TT genotypes were 67.4%, 19.6% and 13.0% in the intrauterine HBV infection group, and 45.2%, 30.1% and 24.7% in the normal immune children group, respectively. A significant difference was found in the frequency distribution of IFN-gamma+874 genotype between the two groups (chi2 = 5.102, P = 0.02389). In the intrauterine HBV infection group the AA genotype was more common than in the normal immune group. Frequency of IFN-gamma+874A allele was 77.17% in the intrauterine HBV infection group, and 60.27% in the normal immune children group. In the intrauterine HBV infection group the IFN-gamma+874A allele was more common than in normal immune group. A significant difference was found in the frequency distribution between the two groups (chi2 = 7.238, P = 0.02389, OR = 2.228, 95% CI = 1.244-3.992). (CA12)+/(CA12)+ of IFN-gamma CA microsatellite polymorphism was 11.90% in the intrauterine HBV infection group and 26.47% in the normal immune children group. A significant difference was found in the frequency distribution between the two groups (chi2 = 5.64, P = 0.0176). Frequency of IFN-gamma CA repeat was 25% in the intrauterine HBV infection group and 43.38% in the normal immune children group. The frequency of IFN-gamma CA repeat was less in the intrauterine HBV infection group than in normal immune group. A significant difference was found in the frequency distribution between the two groups (chi2 = 7.548, P = 0.0060). CONCLUSION: There is a relationship between IFN-gamma+874A/T SNP and intrauterine HBV infection as well as between IFN-gamma CA microsatellite polymorphism and intrauterine HBV infection. IFN-gamma gene polymorphism might be important in determining individual's susceptibility to intrauterine HBV infection.

Transformation of hepatitis B serologic markers in babies born to hepatitis B surface antigen positive mothers.

AIM: To better understand the clinical significance of hepatitis B serologic markers in babies born to hepatitis B surface antigen (HBsAg) positive mothers, the incidence of maternal serologic markers of hepatitis B via placenta and its transformation in these babies were investigated. METHODS: Mothers with positive HBsAg were selected in the third trimester of pregnancy. Their babies received immunoprophylaxis with hepatitis B immunoglobulin and hepatitis B vaccine after birth, and were consecutively followed up for hepatitis B serologic markers and HBV DNA at birth, mo 1, 4, 7, 12, and 24. RESULTS: Forty-two babies entered the study, including 16 born to hepatitis B e antigen (HBeAg)-positive HBsAg carrier mothers and 26 to HBeAg-negative HBsAg carrier mothers. Apart from four babies born to HBeAg-positive carrier mothers and demonstrated persistent positive HBeAg eventually became HBV carriers, all other babies developed anti-HBs before 12 mo of age. Among the other 12 babies born to HBeAg-positive carrier mothers, HBeAg was detected in 7 at birth, in 4 at mo 1, and in none of them thereafter. No antibody response to the transplacental HBeAg was detected. Among the babies born to HBeAg-negative carrier mothers, anti-HBe was detected 100% at birth and mo 1, in 88.5% at mo 4, in 46.2% at mo 7, in 4.2% at mo 12 and none in mo 24. Among all the immunoprophylaxis-protected babies born to either HBeAg-positive or HBeAg-negative carrier mothers, anti-HBc was detected in 100% at birth, mo 1 and mo 4, in 78.9% at mo 7, in 36.1% at mo 12 and in none at mo 24. CONCLUSION: HBeAg can pass through human placenta from mother to fetus and become undetectable before 4 mo of age, but no antibodies response to the transplacental HBeAg can be detected till mo 24 in the immunoprophylaxis-protected babies. The sole existence of anti-HBe before 1 year of age or anti-HBc before 2 years of age in babies born to HBsAg carrier mothers may simply represent the transplacental maternal antibodies, instead of indicators of HBV infection status.

Relationship between cytokines gene polymorphism and susceptibility to hepatitis B virus intrauterine infection.

BACKGROUND: The influences of genomic background are confirmed in more diseases. Immunologic tolerance after intrauterine infection of hepatitis B virus is considered to occur in T cells. Cytokines work effectively in eliminating virus by immune system after hepatitis B virus infection. To explore the relationship between cytokines (tumor necrosis factor-alpha, interferon-gamma, interleukin-4 and interleukin-10), which expressed abnormal quantity in the peripheral blood to intrauterine hepatitis B virus infectious children, gene single nucleotide polymorphism (SNP) and susceptibility to hepatitis B virus intrauterine infection. METHODS: This is a cross sectional study of molecular clinical epidemiology. The subjects in this study were selected from outpatients of hepatitis B vaccine follow-up special clinics of our hospital in the period. According to intrant criteria, the high risk children of hepatitis B virus (HBV) intrauterine infection were divided into immune failure group (group I); and immune effective group (group II) and non high risk children belonged to the control group. Four gene SNP sites of TNF-alpha -238, IFN-gamma +874, IL-4 -590 and IL-10 -1082 were determined by real-time quantitative fluorescent polymerase chain reaction (PCR). RESULTS: The significant differences of TNF-alpha -238 A allele frequency were found between group I and group II (chi(2) = 6.797, P < 0.05) and between group I and the control group (chi(2) = 9.513, P < 0.05). No evident differences of TNF-alpha -238 A were found between group II and control group (chi(2) = 0.047, P > 0.05); the significant differences of IFN-gamma +874 A allele frequency were found between group I and group II (chi(2) = 7.238, P < 0.05), and between group I and the control group (chi(2) = 5.199, P < 0.05). No evident differences were found between group II and the control group (chi(2) = 0.602, P > 0.05); the significant differences of IL-4 -590 C/T allele frequency were not found between group I and group II (chi(2) = 0.632, P > 0.05), also group I and the control group (chi(2) = 0.584, P > 0.05), and the group II and the control group (chi(2) = 0.004, P > 0.05) respectively; The significant differences of IL-10 -1082 G allele frequency were found between group II and group I (chi(2) = 10.359, P < 0.001), and between group II and the controls (chi(2) = 35.418, P < 0.001), but the significant differences were not found between group I and the control group (chi(2) = 1.759, P > 0.05). CONCLUSIONS: This study suggested the possibility that the TNF-alpha -238 A allele and IFN-gamma +874 A allele were associated with HBV intrauterine infection. There was no evident relationship between IL-4 -590 C/T allele SNP and susceptibility to HBV intrauterine infection, but the IL-10 -1082 G allele was associated with preventive efficacy to HBV intrauterine infection.

[Relationship between genetic polymorphism of tumor necrosis factor-alpha and susceptibility to intrauterine HBV infection].

OBJECTIVE: To study the possible relationship between tumor necrosis factor (TNF)-alpha-238G/A gene polymorphism and the susceptibility to intrauterine HBV infection. METHODS: Two hundred and fifty-six children, including 130 infants born to HBsAg positive mothers were divided into two groups: forty-five children with intrauterine HBV infection (group I) and 85 children without intrauterine HBV infection (group II), with a control group of 126. TNF-alpha-238G/A gene polymorphism was examined in all 256 children, by means of real-time quantitative fluorescent PCR. RESULTS: A significant difference of TNF-alpha-238A allele frequency was found between group I and group II (x2=6.797, P=0.009), and between group I and the controls group (x2=0.047, P=0.002), but there was no significant difference between group II and the control groups (x2=0.047, p=0.828). CONCLUSION: This study found that genetic polymorphism of tumor necrosis factor-a was associated with intrauterine HBV infection

[The first confirmed pediatric case with H7N9 avian influenza virus infection in China].

OBJECTIVE: To understand the clinical and epidemiological aspects of avian influenza A (H7N9) virus infection in children. METHOD: The clinical data of the first confirmed pediatric case of avian influenza A(H7N9) virus infection were collected, and the epidemiological information, presenting symptoms, laboratory investigation, management and outcome were analyzed. The data of the pediatric cases were also compared with those of the adults cases. RESULT: The case reported in this paper was a previously healthy 3.6-year-old boy residing in rural area of Shanghai. He had onset of fever and mild rhinorrhea on 31 March 2013 and he was afebrile and well since April 3. Influenza A (H7N9) virus was detected in his nasopharyngeal sample collected on 1 April through national Influenza-like Illness surveillance using real-time reverse transcriptase PCR and virus culture.His family raised domestic poultry with no apparent disease and there was no virological evidence of H7N9 infection. Monitoring and testing of 16 contacts had not found any secondary infection. CONCLUSION: The clinical course of H7N9 avian influenza virus infection in children was relatively mild as compared to adult cases. The source of infection and detail of exposure for children have not been known yet. Continued surveillance studies of mild and severe respiratory disease and subclinical infection are essential to further characterize the epidemiology and clinical spectrum of this emerging H7N9 virus infection in children.

[Two cases of Shwachman-Diamond syndrome with genetic confirmation and literature review].

OBJECTIVE: To study clinical features and gene mutations in Shwachman-Diamond syndrome (SDS), a rare autosomal recessive disease, in children. METHOD: Clinical manifestations, laboratory examinations, image studies, and genetic testing of two cases with SDS were presented, analyzed, and discussed; 311 SDS cases from the related literature since 2004 were reviewed. RESULT: (1) The two cases both presented with characteristic exocrine pancreatic insufficiency evidenced by abnormal pancreas on imaging and growth retardation, persistent or intermittent neutropenia (<1500×10(6)/L) and/or anemia, and skeletal abnormalities. Analysis of the SBDS gene revealed the same compound heterozygous genotype (c.183_184TA > CT, c.258+2T > C) for both subjects. This genotype is the result of the inheritance of abnormal alleles from both healthy parents. (2) Among 311 cases, 75 cases having complete clinical data were characterized by exocrine pancreatic dysfunction (61/75; 81.3%), hematologic abnormalities with single- or multi-lineage cytopenia (64/75; 85.3%), and bone abnormalities (47/75; 62.7%). c.183_184TA > CT, c.258+2T > C, and c. [ 183_184TA > CT; 258+2T > C] are the major types of SBDS gene mutation(85/138;61.6%). CONCLUSION: SDS is characterized by exocrine pancreatic dysfunction with malabsorption, malnutrition, and growth failure; hematologic abnormalities with single- or multi-lineage cytopenia, and bone abnormalities. The diagnosis of SDS relies on a combination of clinical features and gene-based tests. The SDS patients need long term follow-up and management.

[Clinical characteristics and molecular epidemiology of the novel influenza A (H1N1) infection in children in Shanghai].

OBJECTIVE: To investigate the epidemiological features, genetic drift in the epitopes of hemagglutinin (HA) of the novel influenza A (H1N1) virus and oseltamivir-resistant variants characterized by H275Y and N295S mutations in children in Shanghai since the outbreak. METHOD: Between June 2009 and May 2012, a prospective surveillance study was carried out in Shanghainese children who attended the outpatient clinic of Children's Hospital of Fudan University for influenza-like illness. One-step real-time fluorescence quantitative RT-PCR was performed to detect seasonal influenza A and influenza B virus and the novel influenza A (H1N1) virus in the respiratory samples. Genetic drift from the vaccine strain in HA epitopes of the novel influenza H1N1 virus and the molecular markers associated with oseltamivir resistance in neuraminidase (NA) were analyzed. RESULT: Out of 3475 enrolled cases, the novel influenza A (H1N1) virus was confirmed virologically in 222 (6.4%) otherwise healthy children with 133 (59.9%) being boys and 89 (40.1%) girls. The median ages of children with the novel influenza A (H1N1) virus infection during the first wave from August 2009 to February 2010 and the second wave from December 2010 to February 2011 were 53.5 months and 32.0 months, respectively (Z = -4.601, P = 0.000); 119 (46.9%) had the close contact with persons suffering from fever or respiratory infection, of whom, 68 (57.1%) contacts were family members and 47 (39.5%) contacts were classmates. During the outbreak in 2009-2010 season, 66 (40.9%) were exposed to primary index cases, school students were the major exposure subjects, accounting for 50.0%. The nucleotide sequences of HA1 gene were highly homologous between the vaccine strain A/California/07/2009 and Shanghai circulating novel influenza A (H1N1) strains and only S83P mutation in epitope E of HA was detected inclusively in the circulating strains. The H275Y and N295S amino acid mutations associated with oseltamivir resistance were not found in the circulating novel influenza (H1N1) strains. CONCLUSION: Two major waves of the novel influenza A (H1N1) outbreaks occurred in Shanghainese children during 2009-2011. Institutional children were the major affected individuals during the 2009 pandemic wave. Households and schools were the main sites of transmission among children during influenza pandemic. Influenza vaccination should be enhanced in children and their close family contacts. The novel influenza A (H1N1) virus in Shanghai has not undergone significant genetic changes. Oseltamivir is effective for the treatment of the novel influenza A (H1N1) virus.

Seroprevalence of Bordetella pertussis antibody in children and adolescents in China.

BACKGROUND: This multicenter study was undertaken to investigate the serologic evidence of antibodies to Bordetella pertussis toxin (IgG-PT) in children and adolescents. METHODS: IgG-PT value in a single serum collected from 1616 children and adolescents was measured by enzyme-linked immunosorbent assay in the Food and Drug Administration (FDA)-units per milliliter from November 2008 to October 2009. The relationship between time since infection and IgG anti-PT levels were analyzed and the estimated age-specific incidences of infection were calculated. RESULTS: The sera IgG-PT geometric mean concentrations of the samples were 1.7 FDA-U/mL. The sera protective rates of all the subjects were 6.6% (95% confidential interval [CI]: 5.4%, 7.8%). The rates in the group aged 2 years was 9.2% (95% CI: 3.5%, 14.9%), which was significantly higher than in those aged ≥ 3 years (χ = 1615, P = 0.000). In the group aged ≥ 3 years, 4.0% (95% CI: 3.0%, 5.0%) of the individuals tested showed an IgG-PT level ≥ 40 FDA-U/mL, which was equivalent to an estimated incidence of B. pertussis infection of 7000 (95% CI: 5300, 8800) per 100,000 population per year in the year before serum sampling. There were 2 peaks of estimated incidence. One peak incidence of 9100 (95% CI: 4300, 14000) per 100,000 population per year was found in the population aged >6 to 8 years. Another peak was in the population of 12- to 20-year olds with the estimated incidence of 14,600 (95% CI: 9100, 20100) per 100,000 per year. CONCLUSIONS: The levels of protective antibodies against pertussis were very low in the immunized children aged 2 to 20 years. A booster dose of immunization for older children or adolescents should be an urgent priority. Moreover, using enzyme-linked immunosorbent assay to determine the efficiency of vaccines and even to obtain the serodiagnosis would be beneficial in controlling pertussis.

[A prospective cohort study on community children vaccinated with Haemophilus influenzae type b].

OBJECTIVE: To evaluate the epidemiological effect of Haemophilus influenzae type b conjugate vaccine (Hib). METHODS: Prospective Cohort Study was conducted to detect carrier rate of Hi in unvaccinated and vaccinated children by bacteria culture and Nest-PCR. Carrier rate of Hi and the incidence of lower respiratory tract infection in two groups children were analysed. RESULTS: The carrier rate of Hib in two groups children was very lower. The positive rate of NTHi in unvaccinated children was higher than vaccinated children significantly, which was mainly happened in the Children of 2-3 years old. The incidence of lower respiratory tract infection in unvaccinated children was higher than vaccinated children obviously. The protective effect of Hib vaccine against bronchitis was over 90%. The incidence of bronchitis of Hi culture positive was higher than that of Hi culture negative significantly. CONCLUSION: Children's bronchitis is related to the Hi carrier rate. To inoculate Hib vaccine can reduce the carrier rate of Hi and the incidence of bronchitis.

[Clinical relevance of human bocavirus with acute respiratory tract infection and diarrhea in children: a prospective case-control study].

OBJECTIVE: To explore the causative role of human bocavirus (HBOV) played in acute respiratory infection and diarrhea in children, a case-control study was prospectively conducted to investigate HBOV detection in symptomatic children with acute respiratory tract infection, diarrhea and asymptomatic children. METHOD: Between Oct. and Dec. of 2008, 436 nasopharyngeal aspirates (NPA) from hospitalized children with acute respiratory infection and 150 NPA from asymptomatic children undergoing cardiac operations were consecutively collected. During the same time, 220 stool samples were taken from outpatients with acute watery diarrhea and 200 control specimens were obtained from children without diarrhea. HBOV was screened in all samples by real-time PCR method. HBOV-positive respiratory samples were tested for other 9 common respiratory viruses and Mycoplasma pneumoniae. HBOV-positive fecal samples were also tested for common enteric viruses causing diarrhea. RESULT: HBOV was detected in NPA samples from 45 (10.3%) of 436 symptomatic patients and from 1(0.7%) of 150 asymptomatic control children. There was a statistically significant difference in the detection rates of HBOV between the symptomatic group and the asymptomatic group (P < 0.001). HBOV co-existence with other respiratory pathogens occurred in 44.7% (20/45) of NPA from symptomatic patients. HBOV was detected in 10.3% (43/417) children with community-acquired respiratory infection and 10.5% (2/19) children with nosocomial respiratory infection. Children with HBOV infection were 1.3 to 72 months of age (mean: 18.3 ± 13.6 months). HBOV was found positive in 6 (2.7%) of 220 stool samples from diarrheal outpatients and in 4 (2%) of 200 control samples. All children with HBOV positive detection in the stool samples were less than 4 years old. No statistical significance was found (P > 0.05) in HBOV between diarrhea patients and asymptomatic ones. In addition, 5 of 6 HBOV-positive fecal specimens from children with diarrhea were found co-infected with rotavirus. CONCLUSION: This study supports that HBOV is related to acute respiratory infection in children and HBOV infection usually occurs in infants and young children. However, further study is needed to clarify if HBOV plays a pathogenic role in diarrhea in children.

Urinary copper/zinc ratio: a promising parameter for replacement of 24-hour urinary copper excretion for diagnosis of Wilson's disease in children.

BACKGROUND: Although 24-hour urinary copper excretion is valuable for diagnosis of Wilson's disease, accurate, timed collection entails practical difficulties. This study aimed to investigate the feasibility of morning urinary copper/creatinine or copper/zinc ratio as replacement parameter for diagnosing Wilson's disease. METHODS: Five random urinary samples collected during 24 hours from two inpatients were used to estimate the consistency of urinary copper/creatinine and copper/zinc ratios. The correlation of the ratios with 24-hour urinary copper excretion was studied in 15 patients with liver diseases. The diagnostic value of morning urinary copper/zinc ratio was further studied in 9 children with Wilson's disease and 22 children with other liver diseases. RESULTS: The coefficients of variation of urinary copper/creatinine and copper/zinc ratios during 24 hours were 12.5% and 9.3% respectively. The morning urinary copper/creatinine ratio, copper/zinc ratio, and 24-hour urinary copper excretion were correlated well. The area under receiver-operating characteristic curve was comparable between the morning urinary copper/zinc ratio and 24-hour urinary copper excretion (0.983 vs. 0.977). CONCLUSION: Morning urinary copper/zinc ratio seems to be a promising parameter in replacement of 24-hour urinary copper excretion for diagnosis of Wilson's disease.

Human bocavirus in children with respiratory tract infection in Shanghai: a retrospective study.

BACKGROUND: Human bocavirus (HBoV) was first reported in 2005. The worldwide presence of HBoV in children with acute respiratory tract infection (ARTI) has been confirmed. This study aimed to understand the prevalence and clinical features of HBoV in children with ARTI in Shanghai and explore the causative implication of HBoV in ARTI. METHODS: We retrospectively reviewed the medical records of 349 hospitalized children with ARTI between November 2006 and January 2007. From these children, 351 nasopharyngeal aspirate samples were collected; 325 of the samples were obtained from those with community-acquired ARTI and 26 from those with hospital-acquired ARTI. All samples were routinely screened for seven common respiratory viruses by immunofluorescence and further tested for HBoV by polymerase chain reaction. RESULTS: HBoV was detected in 16 (4.6%) of the 351 samples, and it was the second most commonly detected virus after respiratory syncytial virus. Three (19%) HBoV-positive samples were dual infection with respiratory syncytial virus or parainfluenza virus type 3. Of the 325 children with community-acquired ARTI, HBoV was identified to be positive in 11 (3.4%), of whom 6 were diagnosed with pneumonia with patchy or interstitial infiltrates in the lung indicated by chest radiography, 3 with bronchitis, and 2 with bronchial asthma exacerbation with attendant lung infection. Out of the 26 children with nosocomial ARTI, 5 (19.2%) had bronchitis which was found to be HBoV positive without co-detection of other viruses. The HBoV-positive children were aged 1.7 months to 43 months and their mean age was 13.7 months. Sixteen (100%) children had cough, 11 (68.8%) had wheezing, and 10 (62.5%) had fever. CONCLUSIONS: HBoV was circulating in Shanghai during the study period, and which was detected frequently in children with ARTI. HBoV was found to be associated with community-acquired ARTI and may play a pathogenic role in nosocomial ARTI.