Objective: To fully investigate the roles of gene variations associated with lipid metabolism in pediatric non-alcoholic fatty liver disease(NAFLD). Methods: One hundred obese children who were admitted to the gastroenterology department of Shenzhen Children′s Hospital from September 2017 to September 2018 meeting the inclusion criteria were collected.There were 66 males and 34 females aged 8-18 years.Exon sequencing was performed on blood samples from 100 subjects including 39 children with NAFLD(NAFLD group) and 61 healthy obese children(control group). The mutations of genes in lipid metabolism were investigated, and the functions of the variants were further evaluated through PPI analysis and Go term enrichment analysis and software tools which could predicts possible impact on the structure and function of proteins. Results: There were no significant differences between NAFLD and control group in gender and age(all P>0.05). Body mass index(BMI) and waist in the control group were significantly lower than those of NAFLD group(all P<0.000 1). PPI showed that protein microsomal triglyceride transfer protein microsomal triglyceride transfer protein (MTTP), apolipoprotein B (APOB) and Hepatic lipase C (LIPC) were directly interacted.Go analysis showed that the most enriched pathway were triacylglycerol, acylglycerol, neutral lipids, glycerol ether and organo ether (P<0.001). Two variants (chr4: 100504575: G>C, chr4: 100510903: A>G) located in MTTP were significantly differently distributed between 2 groups(all P=0.002), and a potential pathogenic mutation could exist in rs2306986 site. Conclusions The findings of this study indicate that lipid metabolism plays an important role in NAFLD and rs2306986 in MTTP was associated with higher susceptibility to NAFLD.

Objective To monitor the clinical epidemiology and etiology of acute diarrhea in children in the outpatient setting in Shanghai .Methods An active surveillance study in Children′s Hospital of Fudan University between August 2013 and July 2014 was conducted .Outpatient children with acute diarrhea were enrolled in this study and stool samples were collected .Pathogens including norovirus ,diarrheagenic Escherichia coli (DEC) , nontyphoidal Salmonella spp .(NTS),Campylobacter,Shigella,pathogenic vibrio and Yersinia enterocolitica were identified and typed .The χ2 test was used for statistical analysis .Results Of the 881 stool samples from enrolled children , the pathogens included into the target detection were identified in 246 (27 .92% ) cases . Norovirus ,DEC ,NTS ,Campylobacter and Shigella were detected in 98 (11 .12% ) cases ,74 (8 .40% ) cases , 61 (6 .92% ) cases ,34 (3 .86% ) cases and 2 (0 .23% ) cases ,respectively .Neither pathogenic vibrio nor Yersinia enterocolitica was identified .Children younger than 36 months old (3 .27% ,26/794) had a lower risk (χ2=7 .41 ,P=0 .006) of Campylobacter infection compared with older children (9 .20% ,8/87) .Vomiting (37 .76% ) and watery diarrhea (21 .34% ) were more commonly seen in children with norovirus infection;fever and mucous stool were commonly seen in diarrheal children with NTS infection (40 .98% and 21 .31% ,respectively) and Campylobacter infection (29 .41% and 26 .47% ,respectively) .Conclusion Enteric pathogens play a major role in childhood acute diarrhea in Shanghai .Continuous monitoring of enteric pathogens will be helpful for reasonable treatment and prevention of acute diarrhea in children .

Objective To monitor the epidemic pattern of influenza in children during the 2011-2012 season in Shanghai and to evaluate the socioeconomic burden of influenza in children.Methods We carried out a prospective surveillance program on influenza among children who visiting the outpatient clinic for influenza-like illness (ILI) between June 2011 and May 2012.Respiratory samples as well as related demographic and clinical data were obtained from the enrolled cases.Socio-economic burden was evaluated using the questionnaires for some of the confirmed cases during the outbreak.Results Out of the 1 119 enrolled cases,influenza viruses were virologically confirmed,using the RT-PCR in 370 (33.1％) otherwise healthy children.Among them,109 (9.7％) were positive for influenza A/H3N2 viruses,and 279 (24.9％) were positive for influenza B viruses.The 2011-2012 seasonal outbreak of influenza among children with Shanghai residency started with the major outbreak of influenza B during December 2011-Feburary 2012,followed by the smaller outbreak of influenza A/H3N2 during March-April,2012.A total of 69 influenza A/H3N2-infected cases and 163 influenza B-infected cases were surveyed to evaluate the influenza-associated disease burden.The average costs per case were 706.10 Yuan and the average indirect costs per case incurred by the work loss of family members were 293.80 Yuan,with the total average costs per case were 999.90 Yuan.Mean visits to medical settings were 2.7,with antibiotics used in 67.2％ of the cases.Secondary household cases were seen in 21.1％ of the cases.Pneumonia was diagnosed in 5.6％ of the cases.The burden of disease increased from both influenza A/H3N2 and influenza B but without significant differences between them.Conclusion Influenza A/H3N2 and influenza B viruses caused outbreaks of influenza in children with Shanghai residency during the 2011-2012 season.Socioeconomic burden of influenza in children showed significantly direct impact on the sick children and an indirect impact on their families.Influenza vaccination should be recommended in children to reduce the disease burden.

Objective:To investigate the serum measles antibody in children with tumor and to provide the clinical evidence for measles vaccination strategy for this special population.Methods:From January 2016 to December 2018, the blood samples of children who were diagnosed with hematological malignancy or solid tumors and received chemotherapy in the Department of Hematology or Oncology Surgery of Children′s Hospital of Fudan University were collected. Enzyme-linked immunosorbent assay was used to quantitatively detect the level of measles IgG antibody, and dynamically monitor the changes of measles antibody level during chemotherapy. Kruskal-Wallis test and chi-square test were used for statistical analysis.Results:A total of 441 children with tumors were enrolled, with the positive rate of measles antibody of 79.1%(349/441), and only 43.3%(191/441) of children had the protective level of IgG antibody. There was a statistically significant difference of the antibody protection rate in children aged0.05). The protection rate of serum measles antibody in children with hematological malignancy and solid tumor were 45.6%(78/171) and 41.9%(113/270), respectively, and there was no statistically significant ( P>0.05). There were 16.3%(16/98) of children who were observed to lose the pre-existing protective antibody during chemotherapy. There was no statistically significant difference of the protection rate of serum among children who had finished chemotherapy 0.05). Conclusions:Serum measles antibody is below the protective level in more than 50% of children with malignancy after chemotherapy. Chemotherapy can compromise the protective antibody against measles. It is recommended for this special population to re-schedule measles vaccine after individualized evaluation to acquire the immuneprotection against measles.

Objective:To investigate the epidemiological characteristics of hospitalized children with respiratory syncytial virus (RSV)-associated acute lower respiratory tract infection (ALRTI), and to analyzed the risk factors for severe infection.Methods:The epidemiological and clinical data of hospitalized children with ALRTI and positive RSV test from Children′s Hospital of Fudan University from January 2013 to December 2018 were retrospectively analyzed.The hospitalized children from October 2016 to November 2017 were selected by random singular sequence and divided into severe infection group and non-severe infection group. The clinical data of the two groups were compared. Multivariate logistic regression analysis was used to analyze the risk factors of severe RSV-associated ALRTI.Results:A total of 34 192 hospitalized children were diagnosed with ALRTI, and 8 113(23.73%) children were positive for respiratory tract viruses, including 4 028(11.78%) children with RSV infection, which was higher than other common respiratory tract viruses. Among the 4 028 RSV-positive children, 2 550(63.31%) were under six months of age, 3 623(89.95%) were under two years of age. The detection rates of RSV in spring, summer, autumn and winter were 6.47%(553/8 551), 2.46%(176/7 161), 12.85%(1 042/8 111) and 21.77%(2 257/10 369), respectively. In 347 hospitalized children with RSV-associated ALRTI, 54 cases were severe cases. Multivariate logistic regression analysis showed that RSV-positive patients complicated with respiratory diseases ( Z=3.43), cardiovascular diseases ( Z=4.96), non-exclusive breast-feeding ( Z=-1.97) and premature birth ( Z=-1.98) were independent risk factors for severe RSV-associated ALRTI (all P<0.050). Conclusions:RSV is the most important and common viral pathogen in hospitalized children with ALRTI in Shanghai, and infants under six months of age are the most susceptible to RSV. RSV patients complicated with respiratory diseases, cardiovascular diseases, non-exclusive breast-feeding and premature birth are more likely to develope severe RSV-associated ALRTI.

Objective:To monitor the epidemiological characteristics of viral etiology in children with influenza-like illness and to guide the prevention and management of acute respiratory tract infections in childhood.Methods:Nasopharyngeal swabs were collected from the outpatient children seeking medical care in Children′s Hospital of Fudan University, Shanghai for influenza-like illness between January 2015 and December 2018. Multiplex real-time polymerase chain reaction was performed to detect respiratory syncytial virus (RSV), influenza virus (Flu), adenovirus (ADV), parainfluenza virus (PIV, type Ⅰ to type Ⅳ) and enterovirus (EV), and the epidemiological data were analyzed. Chi-square test was used for statistical analysis.Results:A total of 2 271 patients with influenza-like illness were enrolled, age range from two months to 182 months old, 1 280 cases(56.4%) were positive for the target respiratory viruses tested on respiratory samples. The detection rates of FluA, FluB, PIV, EV, ADV, RSV were 15.1%(343/2 271), 12.5%(284/2 271), 8.4%(191/2 271), 7.8%(177/2 271), 5.1%(116/2 271) and 6.7%(152/2 271), respectively.The detection rates of influenza virus were statistically different among the age groups ( χ2=39.33, P<0.05), which showed an increasing trend with the increasing ages. The detection rate of RSV was 9.7%(35/361) in infant group from zero to 12 months old, which was higher than other age groups. Usually, FluA had two epidemic peaks during the winter and summer seasons, the epidemics of FluB and RSV peaked during the winter season, and EV and PIV were more prevalent in the summer season. Conclusions:Influenza virus remains the most common viral pathogen responsible for childhood influenza-like illness in Shanghai.Influenza virus has high incidence in winter.Widely influenza vaccination is highly recommended for the effective prevention the influenza outbreaks.Continuous monitoring the epidemic trend of viral respiratory infections is imperative for the prevention and control of diseases.

OBJECTIVETo monitor the epidemiology of norovirus infection in diarrheal children in Shanghai between 2009 and 2011 and characterize the genotypes of norovirus strains.

METHODThe stool samples were collected from children visiting outpatient clinic for acute non-dysenteric diarrhea between 2009 and 2011.One step real-time RT-PCR was used for screening norovirus genogroups GI and GII. The genotypes of norovirus genogroup GII were classified based on the nucleotide sequences of both partial capsid and polymerase fragments.

RESULTA total of 2 288 outpatient children with acute diarrhea were included in this study, out of whom, 531 (23.1%) were positive for norovirus in the fecal specimens based on real-time RT-PCR test.Norovirus was prevalent throughout the year and an increased activity of norovirus infection was usually observed between July and October. Children <4 years of age accounted for 95.2% of norovirus-infected cases, and the detection rate of norovirus was significantly higher in diarrheal children <4 years than in those ≥ 4 years (24.4% vs. 10.7%,χ(2) = 10.66, P < 0.05).Of 531 norovirus-positive specimens, 4 (1.7%) were positive for genogroup GI and 527 (98.3%) positive for genogroup GII. Seven distinct capsid genotypes were identified in 234 norovirus strains, including 153 (64.4%) GII.4 (9 belonging to 2010 variants and 145 belonging to 2006b variants), 66 (27.6%) GII.3, 7 (2.9%) GII.2, 6 (2.5%) GII.6, 4 (1.7%) GII.12, 1 (0.4%) GII.7 and GII.14 in each. Seven polymerase genotypes were identified in 244 norovirus strains, including 189 (77.5%) GII.4 (14 belonging to 2010 variants and 175 belonging to 2006b variants), 47 (19.3%) GII.12, 2 (0.8%) GII.16, GII.b and GII.g in each, 1 (0.4%) GII.2 and GII.6 in each. A new GII.4-2010 (New Orleans) variant was first detected in June 2010 and sporadically circulated afterwards.Of 198 norovirus strains in which both polymerase and capsid genotypes were determined, 56 showed discordant results, indicating potential norovirus recombinants. The common discordant combinations of the polymerase and capsid genotypes were GII.12/GII.3 (69.6%) and GII.4/GII.3 (8.9%).

CONCLUSIONNorovirus is a common causative agent responsible for diarrhea in Shanghai children over the three years and norovirus-associated diarrhea was epidemic year round with high activity in late summer and autumn in Shanghai.Infants and young children are susceptible to norovirus infection. The circulating norovirus showed genetic diversity. The GII.4-2006b variant continued to predominate in Shanghai during the period of 2009-2011 despite the emergence of the novel GII.4-2010 (New Orleans) variant.

Adolescent ; Caliciviridae Infections ; epidemiology ; virology ; Capsid Proteins ; genetics ; Child ; Child, Preschool ; China ; epidemiology ; Diarrhea ; epidemiology ; virology ; Feces ; virology ; Female ; Gastroenteritis ; epidemiology ; virology ; Genetic Variation ; Genotype ; Humans ; Infant ; Male ; Molecular Epidemiology ; Norovirus ; classification ; genetics ; isolation & purification ; Prevalence ; RNA, Viral ; genetics ; isolation & purification ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA

Children with certain comorbidities and immunocompromising conditions are highly vulnerable to SARS-CoV-2 infection. Vaccination against SARS-CoV-2 is an important strategy to reduce death， critical illness and overall disease burden. With the evolving and increasing transmission of SARS-CoV-2， universal vaccination is essential to achieve this goal. Children with special medical conditions are considered as the priorities for SARS-CoV-2 vaccination. However， vaccine hesitancy towards the implementation of SARS-CoV-2 vaccination currently remains an urgent challenge. In order to promote the sustainable vaccination for those children in Shanghai as well as China， Shanghai municipal center for disease control and prevention， together with the national children’s medical center， children’s hospital of Fudan university and the expert group on immunization planning of the Shanghai preventive medicine association， organized a consensus expert working group to formulate the evidence-based recommendations and implementation suggestions for children with common chronic diseases， allergy history， diseases involving adverse events related to vaccination， and immunocompromising conditions， based on the published evidence of SARS-CoV-2 vaccination for populations and children with special medical conditions.