Objective To investigate the sequences of the 3' end of genomes from enterovirus 71 isolated from pediatric patients with different symptoms in Beijing during 2008-2009.Methods Clinical specimens were collected from pediatric patients suffering from hand,foot and mouth disease(HFMD)and/or with neurological complications who visited the affiliated Children's Hospital during the epidemic seasons of 2008 and 2009 in Beijing.The samples were inoculated into the Vero cell line,and the virus isolates were further identified by nested reverse transcription-nested PCR(RT-nPCR)assay using universal enterovirus primers,type specific primers for EV71 and CA16.The 3' end of genomes(including 3D and 3' UTR regions)from 10 EV71 strains derived from various clinical presentations were amplified and sequenced.Results Analysis of the nucleotide sequences of the amplified fragments showed that the 3' end of genomes of 10 EV71 isolates include the 3D region of 1386 nucleotides(nt)encoding the 3D polymerase(3Dpol,462 amino acids),the terminator codon TGA and 3' UTR of 81 nt.Nucleotide sequence identities among 3D regions from these 10 EV71 isolates were in the range of 95.8%-99.6%,while the nucleotide sequence identities for 3' UTR were 96.3%-100%.The majority of nucleotide changes were located at the third codon positions which caused silent mutations,thus the amino acid sequence changes of 3Dpol among those 10 EV71isolates were scanty.The residues 140 and 263 which were R and 1 were substituted by K and V,respectively in 3 of 4 neurovirulent strains,whereas only 1 of 6 strains from mild cases had these 2 amino acid changes.The sequences of the 3D and 3' UTR regions of 10 EV71 isolates were compared to the representative strains of known genotypes from the GenBank.The nucleotide and amino acid sequences of 10 EV71 isolates in the 3D region exhibited highest homology to the subgenotype C4 of EV71(92.7%-94.2%and 96.8%-97.6%.respectively).However,3' UTR of 10 EV71 isolates shared the highest nucleotide identity with CA16/G10(88.9%-91.4%).The phylogenetic analysis based on the 3D regions demonstrated that 10 EV71 isolates had the closest genetic relationship with the representative isolate of CA sub-genotype of EV71 and shared more homology with CA16/G10 than other known genotypes of EV71.Conclusion Genetic analysis of the 3' end of genomes from 10 EV71 strains indicated that the 3' end of genome may play a role in the evolution of EV71.

Objective To investigate the etiological agents of hand, foot and mouth disease (HFMD) in children in spring and summer from 2007 to 2008 in Beijing and the characteristics of the disease by virus isolation and to provide the scientific evidence for prevention and treatment for HFMD. Methods During April to August, 2007 and May to September, 2008, 356 clinical specimens including 255 throat swabs and 101 vesicle fluids were collected from 256 patients with HFMD who visited the Children's Hospital Affiliated to Capital Institute of Pediatrics and children with severe HFMD with neural system complications from Ditan Hospital and Youan Hospital All of the specimens were inoculated into Vero cells for virus isolation. After the cell pathogenic effects (CPE) appeared, the isolates were identified by RT-PCR with the universal primers within 5'untranslated region of enterovirus and typed by specific primers for VP1 gene of EV71 and CA16, respectively. The throat swabs from all of 10 severe HFMD were tested for enterovirus by RT-PCR addition to virus isolation. Results Out of 256 patients, 188 were positive for enterovirus by virus isolation, with the overall positive rate of 73.4%. Among the 356 clinical specimens collected from these 256 patients, 239 enterovirus strains were isolated with the overall positive rate of 67.1%. The positive rate for virus isolation from vesicle fluid samples was 75.2% which was higher than the positive rate of isolation from throat swabs (63.9%), but the time for CPE appearing in cell culture showed no significant difference. The positive rate of virus isolation from throat swabs from children with severe HFMD was 50% (5/10) which was lower than overall positive rate (73.4%) from regular HFMD. The RT-PCR typing for virus isolates revealed that among 45 enterevirus strains isolated from the specimens collected in 2007 by the universal primer pairs, 43 were CAI6 (95.6%, 43/45) and 2 were EV71 (4.4%, 2/45), whereas for the specimens collected in 2008, out of 143 enterovirus isolates by PCR with universal primers, 117 were EV71 (82.4%, 117/142) and 24 were CA16 (16.8%, 24/142). All of 10 severe cases were positive for EV71 by RT-PCR directly from clinical specimens. Conclusion CA16 and EVT1 were the etiological pathogens of HFMD in Beijing during 2007 to 2008 HFMD seasons. The dominant type of enterovirus was different between 2007 and 2008. Enterovirus type CA16 was predominant in 2007, whereas EV71 was predominant in 2008. All of severe cases of HFMD in children in this study were caused by EV71.

Objective To investigate the status and clinical and epidemiological characteristics of human metapneumovirus (hMPV) and human bocavirus (HBoV) infections in children with acute respiratory tract infections (ARTIs) in Taiyuan. Methods A total of 549 children with ARTIs from November 2012 to May 2013 and November 2013 to May 2014 were recruited. The pharyngeal swab specimens were collected. The hMPV and HBoV were detected by using real-time PCR. Results In 549 children, 56 children (10.2%) were hMPV positive on swab specimens, 15 children (2.7%) were HBoV positive on swab specimens. The detection rates of hMPV and HBoV in November 2012 to May 2013 were 12.3%and 2.0%, respectively, and in November 2013 to May 2014 were 6.5%and 4.0%, respectively. The detection rate of hMPV was signiifcantly different between two periods (P<0.05), while the detection rate of HBoV has no signiifcant difference between two periods. In different months, the detection rate of hMPV and HBoV showed no signiifcant difference. The highest detection rates of hMPV and HBoV were all in children younger than two years old. The highest detection rate of hMPV was in children with asthmatic bronchitis or bronchiolitis. Conclusion In Taiyuan, during the monitoring periods, the ARITS are associated with childhood hMPV and HBoV infection especially in infants and toddlers. hMPV is one of the most important pathogens in infants and toddlers with wheezing.

Growth differentiation factor-15 (GDF-15) is a distant branch of the transforming growth factor-β (TGF-β) superfamily. Recent studies indicate that GDF-15 plays important physiological roles and has clinical implication in the initiation and development of various cardiovascular diseases. GDF-15 can both be used as a biomarker for the evaluation of cardiovascular disease occurrence and progression and a predictor for the risk stratification and long-term prognosis of cardiovascular diseases. The purpose of this review is to illustrate the latest research progress of GDF-15 in atherosclerosis and acute coronary syndrome obtained through the clinical research and basic experiments in cardiovascular diseases, to provide evidence for the selection of GDF-15 as useful biomarkers in the diagnosis and treatment of cardiovascular diseases.

Objective To analyze the status of occupational hazards in key positions of the small and micro book and newspaper printing enterprises in Beijing City. Methods A total of 16 small and micro printing enterprises in Beijing City were selected as the research subjects using the judgment sampling method. The status of occupational hazard was assessed using on-site occupational health investigations. The volatile chemical components in organic solvents such as inks and cleaning agents used in the workplace, the level of chemical hazardous agents in the air, and noise intensity were detected and analyzed. Results A total of 1 105 workers from 16 small and micro printing enterprises were included. The occupational hazard exposure rate was 22.2% (245/1 105), with chemical hazardous agents and noise exposure rates of 13.5% and 22.2%, respectively. The rate of compliance with occupational health training among the head of the enterprise and the occupational health management personnel, the regular detection rate of occupational hazards in last year, and the rate for the occupational health examination in last year were both 100.0%. The rate for annual update of occupational hazard project reporting was 93.8% (15/16). The usage rates of gas mask and noise-proof earplug were 68.8% (11/16) and 50.0% (8/16), respectively. The effectiveness rates of anti-toxic and noise-reduction facilities were 87.5% (14/16) and 62.5% (10/16). The sign setting rates of chemical hazardous agents and noise warning were 93.8% (15/16). Acetone and isopropanol were found in ink and cleaning agents in 15 printing enterprises, while toluene, xylene, and ethylbenzene were found in three, two, and one enterprise, respectively. Benzene, 1,2-dichloroethane, n-hexane, and trichloroethylene were not found in all 16 enterprises. Both the exposure concentration of short term and exposure concentration of time weighted average of the above chemical hazards were lower than the lower limit of quantitation of the detection method in the workplace and work site air among the 16 printing enterprises, and none of concentration was exceeded the national standard. A total of 240 noise work sites were detected, and the national noise-exceeding rate was 11.2%(27/240). Conclusion Noise hazards are prominent in the small and micro printing enterprises in Beijing City, and attention should be paid to the prevention and protection of noise-exposure. The usage rate of personal protective equipment is not high, and the training and on-site supervision management of protective equipment wearing in workers should be strengthened.

Objective:To summarize the clinical manifestations, diagnosis, treatment and prognosis of acute flaccid myelitis (AFM) in children.Methods:Clinical characteristics of 4 AFM cases from Department of Neurology, Children′s Hospital Affiliated to Capital Institute of Pediatrics, from September 2018 to November 2022, were analyzed retrospectively.Results:The age of 4 children with AFM was 7 years, 4 years and 3 months, 7 years and 1 month, 6 years and 5 months, respectively. There were 2 boys and 2 girls. Prodromal infection status showed 3 children of respiratory tract infection and 1 child of digestive tract infection. The main manifestation was asymmetrical limb weakness after infection, and the affected limb range was from monoplegia to quadriplegia. Cranial nerve injury was involved in 1 child, no encephalopathy. Magnetic resonance imaging in the spinal cord of all 4 children showed long T1 and T2 signals, mainly involving gray matter. Cerebrospinal fluid cell-protein separation was observed in 2 children. Pathogen detected in 1 child pharyngeal swab was enterovirus D68. Antibody IgM to adenovirus was positive in the blood of 1 child. Antibody IgG against Echo and Coxsackie B virus were positive in the blood of another child. After glucocorticoid, human immunoglobulin or simple symptomatic treatment and at the same time under later rehabilitation training, muscle strength recovered to different degrees, but there were disabilities left in 3 children.Conclusions:AFM should be considered in children with acute and asymmetrical flaccid paralysis accompanied by abnormal magnetic resonance imaging signal in the central region of spinal cord, especially post-infection. The effective treatment is limited and the prognosis is poor.

Objective To investigate the prevalence of influenza virus infections in infants and young children during the pandemic period of 2009 influenza A(H1N1)in Beijing.Methods Throat swabs were collected from children visited the affiliated Children's Hospital to Capital Institute of Pediatrics for influenza-like illness from June 1,2009 to February 28,2010.The specific gene segments of 2009 pandemic influenza H1N1 and seasonal influenza viruses were amplified from samples by real-time RT-PCR recommended by WHO and National Influenza Reference Center of China.Results Out of 4363 clinical samples tested by real-time RT-PCR,the total positive rate of influenza A viruses was 29.3%,including 623(14.3%)identified as 2009 pandemic influenza A(H1N1)and 657(15.1%)influenza A viruses without subtype identity.Among those pandemic influenza H1N1 positive,23 were severe cases with 5 deaths.The ages for 618 pandemic influenza H1N1 infected children with completed information were from 14 days to 16 years.The ratio of male to female wag 1.3:1.Among them,25.2% were patients in age group of 1 to 3 years old and distribution of children in age groups of 3 to 6 years old and 6 to 12 years old were similar(about 30.0%).During the survey period,it appeared only one prevalence wave of pandemic influenza H1N1.The positive rate of pandemic H1N1 increased in September and the peak(36.5%of positive rate)was in November and then declined to 2.7%in February 2010.The data from routine influenza virus surveillance from 20-30 clinical samples collected each week indicated an alternative prevalence of seasonal H3N2,pandemic H1N1 and influenza B during this study period.Respiratory syncytial virus(RSV)became predominant in children after the circulating of pandemic H1N1.Conclusion There was an epidemic of pandemic influenza H1N1 in children in Beijing from June 2009 to February 2010,especially in those of preschool and school aged children.Seasonal influenza viruses and pandemic influenza H1N1 were contributed alternatively.

Objective: To investigate the clinical characteristics of respiratory syncytial virus(RSV)bronchiolitis and molecular biological characteristics of RSV in children in Beijing. Method: In a systematic retrospective study, 2 296 nasopharyngeal aspirates (NPA) were collected from children diagnosed with bronchiolitis from July 2006 to June 2016 for respiratory virus screening using direct immunofluorescence assay (DFA). For specimens positive for RSV, subgroup A or B was confirmed by real time RT-PCR and genotype of RSV was determined by amplifying the full G glycoprotein gene and sequencing. Clinical data were evaluated by the modified Tal score to compare the severity between RSV subtypes, as well as genotypes. Statistical analyses were performed using t test, Mann-Whitney U test and χ² test. Result: In 2 296 bronchiolitis cases, 961(41.9%) were RSV positive, including 719(74.8%) RSV A and 236 (24.6%) RSV B. The dominant RSV subtype changed from year to year: A-A-B-B-A-A-B-AB-A-AB and more bronchiolitis cases were identified in RSV A dominant years. Six genotypes of RSV A (NA1, NA2, NA3, NA4, GA5 and ON1) and 5 genotypes of RSV B (BA3, BA7, BA9, BA10 and CB1) were prevalent in Beijing. The dominant genotypes of RSV A were NA1 (55.9%) with high rates (50.0%-100%) before 2014 and ON1 (39.1%), mainly detected after 2014, while BA9 (90.6%) was the absolute dominant RSV B genotype. No significant difference in the severity of bronchiolitis was shown between cases of RSV A and B. Children positive for NA1 were more likely to stay longer in hospital (Median time: 8 days) compared to the group positive for ON1(Median time: 6 days ) (U=1.035, P=0.005) and had higher proportion of moderate to severe degree symptoms (Moderate: 41.0%, Severe: 10.0%) compared with ON1 group (Moderate: 22.9%, Severe: 4.3%) (U=9.785, P=0.008). In the group positive for ON1, more children had fever (ON1: 38.6%, NA1: 15.0%) (χ²=11.064, P=0.001) and more were younger than 3 months(ON1: 54.3%, NA1: 33.0%) (χ²=77.408, P<0.001). Conclusion The dominant RSV subgroup changed from year to year with a shifting pattern. The correlation between RSV genotypes and the severity of disease was documented in the study.

Objective:To investigate the main factors that influence ALT abnormalities in workers exposed to benzene.Methods:In June 2022, data of 613 enterprises with benzene hazards and 585 enterprises with non-benzene hazards in Tianjin in 2021 were collected, and occupational health examination data of 13018 workers with benzene exposure and 13018 workers with non-benzene exposure were collected, and the region, enterprise type, industry classification and enterprise scale of the employer were analyzed. And occupational health examination data of workers with benzene exposure and non-benzene exposure. The effects of personal general situation, occupational history, enterprise information and benzene exposure on alanine aminotransferase were evaluated by additive interaction.Results:Compared with the group of non-benzene-exposed workers, the personal general conditions, occupational history, company information were higher in the benzene-exposed workers, and the differences were statistically significant ( P<0.05). The quantitative analysis of additive interaction found that gender ( RERI=2.632, 95% CI: 1.966-3.297; AP=0.383, 95% CI: 0.311-0.456; S=1.813, 95% CI: 1.530-2.149), age ( RERI=1.142, 95% CI: 0.928-1.356; AP=0.462, 95% CI: 0.371-0.552; S=4.461, 95% CI: 1.800-11.053), length of service ( RERI=-1.199, 95% CI: -1.653--0.745; AP=-0.456, 95% CI: -0.640--0.271; S=0.576, 95% CI: 0.479-0.693), region ( RERI=0.421, 95% CI: 0.148-0.694; AP=0.161, 95% CI: 0.053-0.268; S=1.350, 95% CI: 1.057-1.726), industry classification ( RERI=0.627, 95% CI: 0.345-0.910; AP=0.232, 95% CI: 0.132-0.332; S=1.584, 95% CI: 1.233-2.035) and benzene exposure had a statistically significant additive interaction with abnormal serum ALT. Conclusion:Emphasis should be placed on male workers under the age of 40 in the petrochemical industry, oil storage and transportation, and power production, so as to protect the health of workers more specifically and reduce the risk of disability due to disease.

Objective:To investigate the main factors that influence ALT abnormalities in workers exposed to benzene.Methods:In June 2022, data of 613 enterprises with benzene hazards and 585 enterprises with non-benzene hazards in Tianjin in 2021 were collected, and occupational health examination data of 13018 workers with benzene exposure and 13018 workers with non-benzene exposure were collected, and the region, enterprise type, industry classification and enterprise scale of the employer were analyzed. And occupational health examination data of workers with benzene exposure and non-benzene exposure. The effects of personal general situation, occupational history, enterprise information and benzene exposure on alanine aminotransferase were evaluated by additive interaction.Results:Compared with the group of non-benzene-exposed workers, the personal general conditions, occupational history, company information were higher in the benzene-exposed workers, and the differences were statistically significant ( P<0.05). The quantitative analysis of additive interaction found that gender ( RERI=2.632, 95% CI: 1.966-3.297; AP=0.383, 95% CI: 0.311-0.456; S=1.813, 95% CI: 1.530-2.149), age ( RERI=1.142, 95% CI: 0.928-1.356; AP=0.462, 95% CI: 0.371-0.552; S=4.461, 95% CI: 1.800-11.053), length of service ( RERI=-1.199, 95% CI: -1.653--0.745; AP=-0.456, 95% CI: -0.640--0.271; S=0.576, 95% CI: 0.479-0.693), region ( RERI=0.421, 95% CI: 0.148-0.694; AP=0.161, 95% CI: 0.053-0.268; S=1.350, 95% CI: 1.057-1.726), industry classification ( RERI=0.627, 95% CI: 0.345-0.910; AP=0.232, 95% CI: 0.132-0.332; S=1.584, 95% CI: 1.233-2.035) and benzene exposure had a statistically significant additive interaction with abnormal serum ALT. Conclusion:Emphasis should be placed on male workers under the age of 40 in the petrochemical industry, oil storage and transportation, and power production, so as to protect the health of workers more specifically and reduce the risk of disability due to disease.