Clinical characteristics and molecular epidemiology of the novel influenza A (H1N1) infection in children in Shanghai / 中华儿科杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHOD</b>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.</p><p><b>RESULT</b>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.</p><p><b>CONCLUSION</b>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.</p>

The first confirmed pediatric case with H7N9 avian influenza virus infection in China / 中华儿科杂志

<p><b>OBJECTIVE</b>To understand the clinical and epidemiological aspects of avian influenza A (H7N9) virus infection in children.</p><p><b>METHOD</b>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.</p><p><b>RESULT</b>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.</p><p><b>CONCLUSION</b>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.</p>

Two cases of Shwachman-Diamond syndrome with genetic confirmation and literature review / 中华儿科杂志

<p><b>OBJECTIVE</b>To study clinical features and gene mutations in Shwachman-Diamond syndrome (SDS), a rare autosomal recessive disease, in children.</p><p><b>METHOD</b>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.</p><p><b>RESULT</b>(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%).</p><p><b>CONCLUSION</b>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.</p>

Characteristics of the plasma amino acid spectrum of neonatal intrahepatic cholestasis caused by citrin deficiency / 中华肝脏病杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>The plasma amino acid spectrum may represent a diagnostic indicator for NICCD, particularly the ratio of Cit to Ala.</p>

Epidemiological surveillance of norovirus and rotavirus diarrhea among outpatient children in five metropolitan cities / 中华儿科杂志

<p><b>OBJECTIVE</b>To survey the clinical epidemiological features of norovirus and rotavirus diarrhea among children living in 5 cities.</p><p><b>METHOD</b>A prospective epidemiological investigation was conducted among outpatient children with acute diarrhea between August 2008 and July 2009 in Shanghai, Hangzhou, Guangzhou, Chongqing and Tianjin. The stool samples were randomly collected from children with non-dysentery diarrhea. Group A rotavirus antigen was tested by the kit that applies colloidal gold method in all specimens. GI and GII genogroups of norovirus were detected by one-step real-time reverse-transcription polymerase chain reaction (RT-PCR). The detection rates, seasonality and susceptible age of both viruses-associated diarrhea were analyzed.</p><p><b>RESULT</b>During the one-year period, 5091 fecal samples were obtained, of which 1563 (30.7%) were rotavirus-positive. The detection rates of rotavirus were 29.5% (268/916) in Shanghai, 36.1% (334/926) in Hangzhou, 26.3% (254/968) in Guangzhou, 34.1% (359/1054) in Chongqing and 28.2% (348/1233) in Tianjin, respectively. Among the remaining 3528 rotavirus-negative samples, 1049 (29.7%) were identified to be norovirus-positive. The detection rates of norovirus were 21.2%(136/642) in Shanghai, 31.3% (185/592) in Hangzhou, 24.2% (173/714) in Guangzhou, 31.8% (221/695) in Chongqing and 37.7% (334/885) in Tianjin, respectively. It is estimated that the infection rate of norovirus among outpatients with acute diarrhea is at least more than 20.6% (1049/5092). Of 1049 norovirus strains, 1036 (98.7%) were GII genogroup and 16 (1.5%) were GI genogroup, 3 were mixed with GI and GII genogroups. The 1049 children with norovirus diarrhea aged between 1 month and 14 years with the median age of 10 months (mean: 13.9 ± 16.9 months) and 91.8% were 2 years old or younger. The 1563 children with rotavirus diarrhea aged between 1 month and 11.3 years with the median age of 10 months (mean: 12.9 ± 13.7 months) and 92.5% were 2 years old or younger. The median ages between norovirus-infected children and rotavirus-infected children were significantly different (P < 0.05). The peak seasons of rotavirus diarrhea spanned autumn and winter (from October to February). The peak seasons of norovirus diarrhea presented in the winter and spring (from November to April) in Tianjin. Norovirus became active in April and usually predominantly prevalent in the summer and autumn (from July to October) in Shanghai, Hangzhou and Chongqing. However, norovirus was sporadically prevalent in the spring and detected more commonly in the other seasons in Guangzhou.</p><p><b>CONCLUSION</b>Both rotavirus and norovirus are the major causative agents for childhood diarrhea. The seasonality of rotavirus diarrhea was similar among the 5 cities. Nevertheless, the seasonality of norovirus diarrhea was diverse in the different areas. In Tianjin located in the north of China, norovirus was quite prevalent in the cold season. In the east (Shanghai and Hangzhou) and south-west (Chongqing), norovirus prevailed dominantly in the summer and autumn. In the south (Guangzhou), the activity of norovirus was more obvious in the summer, autumn and winter.</p>

Clinical relevance of human bocavirus with acute respiratory tract infection and diarrhea in children: a prospective case-control study / 中华儿科杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHOD</b>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.</p><p><b>RESULT</b>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.</p><p><b>CONCLUSION</b>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.</p>

Molecular epidemiology of human metapneumovirus in children with acute lower respiratory tract infections in Shanghai / 中华流行病学杂志

Objective To understand the clinical and molecular epidemiologic features of human metapneumovirus (hMPV) in children with acute lower respiratory tract infection (ALRTI)from Oct.2006 to Feb.2008 in Shanghai.Methods We established a reliable and stable diagnostic method of TaqMan-MGB real-time reverse transcription polymerase chain reaction (RT-PCR) to detect hMPV in the clinically manifested respiratory samples.To understand the role of hMPV in children' s ALRTI,we tested other seven common respiratory viruses,using direct immunofluorescence assays (DFA).Results Data was analysed on the rates of detection among patients with respiratory bacteria,mycoplasma pneumonia and chlamydia among the targeted samples and enrolled patients to display the spectrum of respiratory pathogens and the changing pattern of pathogens with time.Of 622 samples,hMPV was detected to be positive in 24 (3.86%) samples.However,the prevalence of hMPV in the winter season of 2006 to 2007 was higher than that in the winter season of 2007 to 2008.The majority of children infected with hMPV were younger than 5 years old.Data from phylogenetic tree analysis further demonstrated A2 genotype hMPV circulating during the study period.Conclusion Respiratory viruses were important respiratory pathogens among children with ALRTI and respiratory syncytial virus.They were the two most common virus which might be followed by hMPV that causing the diseases.We confirmed that hMPV as an important pathogen of ALRTI in the children from Shanghai.

Analysis of 12 children with novel influenza A (H1N1) virus infection / 中华儿科杂志

<p><b>OBJECTIVE</b>Since late March 2009, a novel influenza H1N1 strain emerged in humans in Mexico and the United States. It has rapidly spread to many countries on different continents, prompting unprecedented activation of pandemic preparedness plans. The present study aimed to investigate the characteristics of children with the novel influenza A (H1N1) virus infection.</p><p><b>METHOD</b>Twelve cases with influenza A (H1N1) infection were diagnosed according to the criteria of the Center for Disease Control and Prevention (CDC) of China during 1 May to 15 July 2009 in the Pediatric Hospital of Fudan University were analyzed. Influenza A (H1N1) RNA was detected by RT-PCR in CDC Shanghai China.</p><p><b>RESULT</b>All the 12 children with the novel influenza A (H1N1) virus infection were imported cases, aged from 11 months to 14 years 7 months, 7 of whom were boys, 5 were girls. Five cases contacted closely with influenza A (H1N1) patients; 12 cases had fever and no vomiting or diarrhea; 7 had cough or runny nose or anorexia. One had shortness of breath. Of the 11 cases who could tell about symptoms correctly, 6 had sore throat, 3 had stomachache, and none had muscle pain. Two of the 12 cases had pneumonia, and the disease in 1 of them was fatal and needed intensive care. One case was isolated and treated at home. The 11 cases hospitalized were treated according to the guidance of influenza A (H1N1) diagnosis and treatment issued by the Ministry of Health of China. Ten hospitalized cases were treated with oseltamivir. All the cases recovered completely. The median length of hospital stay was 8.1 days (range, 6 to 16), and the time of negative test results of influenza A (H1N1) RNA from illness onset to collection of samples for viral testing was from 5 to 15 days.</p><p><b>CONCLUSION</b>Symptoms among children with the novel influenza A (H1N1) virus infection were classic and the majority of the cases we treated had a mild clinical course if they were isolated and treated promptly. Antivirals appears to have not had any major adverse effects. More data from different regions and large samples are needed to illuminate the characteristics of children with novel influenza A (H1N1) virus infection.</p>

SLC25A13 gene mutations in Chinese infants with intrahepatic cholestasis and abnormal blood amino acids / 中华肝脏病杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Randomized controlled multi-center trial for treatment of varicella in pediatric patients with hydrochloride valacyclovir / 中华儿科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of hydrochloride valacyclovir in treatment of varicella in pediatric patients between April 2006 and March 2007.</p><p><b>METHODS</b>A randomized controlled multi-center clinical trial was conducted in 5 pediatric centers, i.e., Children's Hospital of Fudan University, Children's Hospital of Zhejiang University, Children's Hospital of Nanjing Medical University, Pediatric Department of Tongji Hospital of Tongji Medical College, Huazhong University of Science & Technology and Children's Hospital, Chongqing University of Medical Sciences. Patients who were clinically diagnosed as varicella without any complications and were beyond 3 years of age were enrolled into the study from the out-patient clinics. The subjects were divided into two groups randomly, one was treated with hydrochloride valacyclovir, the other with ribavirin. There were 128 cases in the group treated with hydrochloride valacyclovir and 132 cases in control group treated with ribavirin. The treatment duration of two groups was five days. The clinical efficacy and safety were evaluated after the first day and the fourth day of the treatment and within three days after the end of the treatment. The clinical efficacy was assessed by efficacy index.</p><p><b>RESULTS</b>(1) The efficacy index on the fourth day of the therapy (0.80 +/- 0.24) in the valacyclovir group was significantly higher than that of ribavirin control group (0.59 +/- 0.37) (t = 5.42, P < 0.01). The efficacy index at the end of the treatment (0.86 +/- 0.14) in the hydrochloride valacyclovir group was also significantly higher than that (0.70 +/- 0.30) of the ribavirin control group (t = 5.43, P < 0.01). (2) In the valacyclovir and ribavirin groups, the effective rates on the fourth day of the therapy were 94.53% and 72.7% respectively (chi2) = 22.38, P < 0.01). The effective rates at the end of the therapy were 99.2% and 88.6%, respectively (chi(2) = 12.60, P < 0.01). The rates of cure of the two groups were 33.6% and 25.0% (chi2) = 2.32, P > 0.05). (3) No severe adverse drug reactions were observed in any of the two groups.</p><p><b>CONCLUSIONS</b>The hydrochloride valacyclovir was safe, reliable and convenient in treatment of uncomplicated varicella in children.</p>

Gene detection and clinical study of rhinovirus isolated from children with acute low respiratory tract infection in Shanghai / 中华传染病杂志

Objective To understand human rhinovirus (HRV) etiology of acute lower respiratory tract infection (ALRTI) in children in Shanghai area and establish a nested reverse transcription- polymerase chain reaction (nested RT-PCR) assay.Methods Three hundred and forty-two naso- pharyngeal secretion (NPS) samples from ALRTI cases who were hospitalized were collected during January 2005—December 2005.Nested RT-PCR techniques were used to detect HRV-specific RNA.The PCR products were sequenced and data of nucleotides were analyzed.The proportion of HRV infection in children with ALRTI,the distribution of gender,age and season,and clinical char- acteristics were also investigated.Results Forty-six (13.5%) of 342 samples were HRV positive detected by nested RT-PCR.The sequences of 15 positive samples shared high homology of 83%- 97% with HRV sequence in GenBank.Within the 15 positive samples,nucleotide homology varied from 64.4% to 98.4%,and the ratio of genetic variation was from 1.6% to 48.3%./00.These 15 ampli- cons attribute to the two branches of HRV cladogram.The sequences of 15 amplieons were highly varied,in which single nucleotide mutation and several nearby nueleotides mutations were found. Ribonucleotide deletion and insertion in the nucleotide sequence was also found.HRV positive sam- ples were detected in 33 boys and 13 girls,respectively.The ratio of infection cases between boys and girls was 2.5:1.Of 46 HRV infected cases,27 (58.7%) were less than 12 months of age and 38 (82.6%) were less than 3 years old.HRV infected ALRTI occured all the year round and peaked from March to May.Of the patients whose NPS samples were HRV positive detected by nested RT-PCR,45 patients were diagnosed with bronchopneumonia and 1 was diagnosed with asthmatic bronchitis.Fever of most patients was moderate.The peripheral blood leukocyte counts in thirty-nine (84.8%) patients were less than 10?10~9/L.Neutrophil percentages in thirty-seven (80.4%) patients were less than 0.50.C-reactive protein of thirty-six (78.3%) patients were less than 8 mg/L. All of these features were the characteristics of viral pneumonia.The complications were not common and conditions of most patients were not severe.All the children were cured.Conclusions This nes- ted RT-PCR technique is highly specific,rapid and convenient for the detection of HRV RNA in NPS of patients with ALRTI and the genome of HRV viruses is highly variable.The incidence of HRV infection predominates in children in Shanghai area.ALRTI of HRV is short of specificity and condi- tions of most patients are not severe and their prognoses are fine.

Relationship between interleukin-12B gene + 1188 polymorphism and the susceptibility to hepatitis B virus intrauterine infection / 中华传染病杂志

10 mU/L (GroupⅡ,71 cases) when they were one year old.There were 40 healthy children in control group. The genomic DNA from the peripheral blood was extracted and polymerase chain reaction (PCR) and sequencing were employed to detect the IL-12B gene 3′UTR+1188 SNP.Results The frequency of AA,AC and CC genotype in GroupⅠwere 25.7%,44.3% and 30.0% respectively,and 36.6%, 47.9% and 15.5% in GroupⅡ,48.8%,39.0%,12.2%,in control group,respectively.The differ- ence of frequency of CC genotype and non-CC genotype between GroupⅠand GroupⅡwas significant (x~2=17.078,P

ABCB11 Gene Variation and Cholestatic Diseases / 实用儿科临床杂志

ABCB11 gene encodes bile salt export pump (BSEP).It is almost exclusively expressed in the canalicular microvilli of liver.It is the principal conveyor of bile acids from hepatocyte cytoplasm into bile canaliculus.It is clearly that BSEP defects can induce progressive familial intrahepatic cholestasis type 2 and benign recurrent intrahepatic cholestasis type 2.ABCB11 gene variation are also responsible for intrahepatic cholestasis of pregnancy,drug-induced cholestasis,primary sclerosis cholangitis and primary bile cirrhosis.This paper reviewed the association of ABCB11 gene variation and these diseases.

Acute Pancreatitis in 106 Children / 实用儿科临床杂志

Objective To understand the clinical features of children with acute pancreatitis.Method Clinical data of 106 in patients in Children′s Hospital with acute pancreatitis from Jul.1991 to Jan.2005 were analyzed retrospectively.Results The most frequent(etiologic) factors of childhood acute pancreatitis were idiopathic(35.8%),mumps virus infection(33.9%)and biliary tract diseases(15%).Abdominal pain(96.2%),vomiting(72.6%)and fever(45.3%) were the most common clinical symptoms.And the most common signs were abdominal tenderness(73.6%),abdominal wall rigidity(17.9%)and abdominal distention(10.6%).Multisystem damage usually occurred in childhood acute pancreatitis.Serum amylase,urinary amylase and serum lipase elevated 84.8%,58.5% and 55%in patients,respectively.Fifty-one percont patients had abnormal ultrasound imaging and 81% had abnormal computed tomographic imaging.In 5 patients who were subjected to endoscopic retrograde cholangiopancreatography(ERCP) and magnetic resonance cholangiopancreatography(MRCP),the pancreaticobiliary system was visualized clearly.Nonsurgical therapy was done in most patients,only 6 cases received surgical therapy.Sixty-five cases were cured and 40 cases straightened up,only 1 case died.The efficiency rate was 99%.Pseudocysts occurred in 2 patients.Conclusions Idiopathic pancreatitis and mumps virus infection are the most frequent etiologic factors for childhood acute pancreatitis.Symptoms and signs such as abdominal pain and abdominal tenderness are the important diagnostic bases of childhood acute pancreatitis.Childhood acute pancreatitis was always accompanied by multisystem damage.Pancreatic enzyme test and radiography test were helpful in the diagnosis of childhood acute pancreatitis.Nonsurgical therapy is the leading therapeutic means of childhood acute pancreatitis.Timely diagnosis and allopathy help to improve the prognosis of childhood acute pancreatitis.Pseudocyst is the primary complication of childhood acute pancreatitis.

Study on the S region gene mutation of hepatitis B virus during prevention of HBV transmission in uterus with hepatitis B immunoglobulin / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the relationship between hepatitis B immunoglobulin (HBIG) injection before delivery and hepatitis B virus (HBV) S gene mutation.</p><p><b>METHODS</b>18 neonates infected with HBV in uterus and their mothers were divided to a) HBIG group (8) in which their mothers received HBIG injection before delivery and b) control group (10) in which their mothers never received any treatment HBV DNA fragments were amplified by nest-PCR from sera of these neonates and their mothers. S gene region of these HBV DNA fragments were directly sequenced and data on mutations was analyzed.</p><p><b>RESULTS</b>There was no significant difference on nucleotide and amino acid changes in the S gene between the HBIG group and the control group. The majority HBV strains of newborn (17/18) were identical to their mother's dominant strains before delivery, including four mutation HBV strains. Among 18 newborns with HBV intrauterine infection, 12 were infected by B type (adw2), and 6 by C type (adrq+).</p><p><b>CONCLUSION</b>Mothers who were asymptomatic HBsAg carrier and received injections ofHBIG before delivery would not be influenced by HBV S gene mutation. HBV intrauterine transmission with or without gene mutation might occur in the third-trimester of pregnancy. Gene mutation of HBV was not the main factor in intrauterine transmission of HBV.</p>

Detection of class I integron and its relation to antimicrobial resistance of Shigella flexneri in children / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate class I integron of Shigella flexneri, its prevalence in children, and its relation to bacterial resistance to antimicrobial agents.</p><p><b>METHODS</b>Totally 51 strains of Shigella flexneri were isolated from fecal samples of children suffering from bacterial diarrhea seen between June 2004 and November 2004 at Children's Hospital of Fudan University. Polymerase chain reaction (PCR) was employed to amplify various integron markers, including intI1, gene cassette region and 3' conserved region of class I intrgron; susceptibility of Shigella flexneri strains to 7 antimicrobial agents was determined by K-B (Kriby-Bauer) method.</p><p><b>RESULTS</b>Forty-six strains of Shigella flexneri had intI gene with a positive rate of 90.2% (46/51); 24 strains of Shigella flexneri were positive for qacEDelta1-sul1, the positive rate was 47.1% (24/51); proportion of the isolates positive for all the three regions of class I integron was 43.1% (22/51); 46 strains of intI positive Shigella flexneri were all positive for ant (3'')-I. Among 46 strains of intI positive isolates, proportions of the isolates positive and negative for qacEDelta1-sul1 were 47.8% (22/46) and 52.2% (24/46), respectively. In the class I integron positive Shigella flexneri, the resistance rates of ampicillin (chi(2) = 10.13, P < 0.01) and chloramphenicol (chi(2) = 19.97, P < 0.01) were significantly higher than those in the class I integron-negative group.</p><p><b>CONCLUSIONS</b>Class I integron was detected in 90.2% of Shigella flexneri in children; carriage of class I integron is related to antimicrobial resistance of Shigella flexneri.</p>

Relationship between cytokines gene polymorphism and susceptibility to hepatitis B virus intrauterine infection / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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).</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

Relationship between cytokine gene polymorphism and susceptibility to hepatitis B virus intrauterine infection / 中华流行病学杂志

<p><b>OBJECTIVE</b>To explore the possible relationship between cytokines (TNF-alpha, IFN-gamma, IL-4 and IL-10), which were expressed abnormal quantity in the peripheral blood to intrauterine HBV infectious children, gene single nucleotide polymorphism (SNP) and susceptibility to HBV intrauterine infection.</p><p><b>METHODS</b>A cross sectional study on molecular epidemiology was carried out. The subjects were selected from outpatients of the hepatitis B vaccine special clinics of our hospital. According to intrant criteria, children under high risk of HBV intrauterine infection were divided into immuno-failure group (group I) and immuno-effective group (group II) while children without high risk were included in the control group. Four gene SNP sites of TNF-alpha-238, IFN-gamma + 874, IL-4-590 and IL-10-1082 region were determined by real-time quantitative fluorescent PCR.</p><p><b>RESULTS</b>Significant differences of TNF-alpha-238 A allele frequency were found between group I and group II (chi(2) = 6.797, P < 0.05) as well as between group I and control group (chi(2) = 9.513, P < 0.05). No evident difference of TNF-alpha-238 A was found between group II and control group (chi(2) = 0.047, P > 0.05). 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 controls (chi(2) = 5.199, P < 0.05) but no significant difference was found between group II and control group (chi(2) = 0.602, P > 0.05). 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), group I and control group (chi(2) = 0.584, P > 0.05), or between group II and control group (chi(2) = 0.004, P > 0.05) respectively. 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 not found between group I and control group (chi(2) = 1.759, P > 0.05).</p><p><b>CONCLUSION</b>This study suggested the possibility that 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 seemed to be associated with preventive efficacy to HBV intrauterine infection.</p>

Detection of enterovirus 71 and coxsackievirus A16 from children with hand, foot and mouth disease in Shanghai, 2002 / 中华儿科杂志

<p><b>OBJECTIVE</b>It was noticed that coxsackievirus A16 (CA16) and enterovirus 71 (EV71) were two major etiological agents of hand, foot and mouth disease (HFMD) in children. Recently there were several large outbreaks of HFMD in the Asia-Pacific region, and there was a propensity to cause severe complications or death in children under 5 years of age. The severe forms were associated with EV71 infection. Although epidemics of HFMD have been reported in the mainland of China, few reports about EV71 as the pathogen of HFMD epidemics are available. The present study was conducted to investigate the causal agent of an HFMD epidemic in children in Shanghai from April to June of 2002.</p><p><b>METHODS</b>Totally 102 specimens (including vesicle fluid, stool and throat swabs) were collected from 72 patients with HFMD. The specimens were inoculated into Vero and/or RD cells. At first all the isolates were respectively neutralized by the RIVM pools of enterovirus antiserum, the type-specific antisera to EV71 or to CA16. Secondly all untyped isolates were tested by RT-PCR assay with two specific primer pairs for VP1 genes of EV71 and CA16 respectively. The EV71 and CA16 were identified depending on the size of PCR products. Sequence analyses of VP1 genes of 9 virus strains were performed by the laboratory of China CDC.</p><p><b>RESULTS</b>Viruses were isolated from 91 specimens from 67 patients. Serotyping by neutralization failed for all the isolates. But the RT-PCR results indicated that the viruses isolated from 78 specimens from 58 patients were identified as positive for CA16 and the isolates from 13 specimens from 9 patients were identified as positive for EV71, the ratio between CA16 and EV71 was 6.4:1. The results of sequence analyses were consistent with those of PCR assay. Two EV71 strains isolated in this study belonged to a new lineage (C4) within genogroup C. One patient with EV71-associated HFMD had a complication of encephalitis with convulsion, shock, coma and dyspnea.</p><p><b>CONCLUSION</b>CA16 and EV71 were the primary causes of HFMD during the epidemic. It was the first report of EV71-associated severe encephalitis occurred in patients with HFMD in Shanghai.</p>

Clinical Cross Sectional Study of Herpes Simplex Virus Infection of Central Nervous System in Newborn Infants / 实用儿科临床杂志

Objective To investigate the prevalence of herpes simplex virus(HSV) infection of central nervous system(CNS) in newborn infant,and analyze its clinical characteristics.Methods Cerebrospinal fluid(CSF) was collected from 40 acute viral infection of central nervous system who were hospitalized during June 2001 to June 2002.Polymerse chain reacton techniques(nested-PCR)was used to detect HSVspecific DNA in CSF,enzyme-linked immunosorbert assays(ELISA)was applied to detect HSV-specific IgM and IgG antibody in CSF and serum specimens.Results Two cases of neonatal patients were HSV-1 DNA PCR positive in CSF,both(mo)-ther were normal during pregnancy without a history of genital herpes.Clinical presentations of one case belonged to disseminated HSV infections and the other was limited to CNS infections.HSV-2 DNA PCR of 40 cases of neonatal patients were negative in CSF.Conclusions The rate of HSV neonatal CNS infection was 5% among viral neonatal CNS infections.HSV type 1 in the period,which showed that HSV type 1 may be the common type of HSV neonatal CNS infections.The result seems to be related to low prevalence for HSV-2(among) pregnancy women in China.