In countries and regions with high vaccination coverage, several vaccine-preventable diseases have been resurged in recent years, such as measles, varicella, pertussis and mumps. Some studies have found that the clinical manifestation and epidemiological characteristics of these diseases were different from those in pre-vaccine era. This article reviewed the clinical and epidemiological features of vaccine-preventable diseases before and after wide immunization implementation, focusing on the situation in China, in order to attract the attention of clinicians, raise awareness, strengthen prevention and control, and promote in-depth research for these diseases.

Objective To investigate the level of IgG antibody to varicella in the healthy population aged 1-19 years in Harbin, China. Methods Random sampling was performed to select 1203 healthy individuals aged 1-19 years in Harbin. According to age, they were divided into ≥ 1 years group (n=240), ≥ 4 years group (n=396), ≥ 7 years group (n=364) and 14-19 years group (n=203). Enzyme-linked immunosorbent assay was used to measure the concentration of varicella-zoster virus (VZV)-IgG antibody in serum, and a concentration of VZV-IgG antibody of ≥ 100 mIU/mL was considered positive, suggesting that the subject had the ability to resist VZV infection. Results The overall positive rate of VZV-IgG antibody was 71.49% (860/1203), and the concentration of VZV-IgG antibody was 447±17 mIU/mL. The concentration of VZV-IgG antibody tended to increase with age (P < 0.05). The positive rate of VZV-IgG antibody in the urban population was significantly higher than that in the rural population (P < 0.05). There was significant difference in the positive rate of VZV-IgG antibody between the populations with different doses of varicella vaccination (P < 0.05), and the population with 2 doses of vaccination had the highest positive rate of VZV-IgG antibody. There was a signifcant difference in the concentration of VZV-IgG antibody between the populations with different medical histories (P < 0.05), and the population with a past history of varicella had the highest concentration. Conclusions Among the healthy population aged 1-19 years in Harbin, there is a signifcant difference in the level of VZV-IgG antibody between the urban and rural populations, as well as between different age groups. Varicella vaccination should be strengthened in areas with a low vaccination rate and the population aged <14 years.

Objective To investigate the alternative antimicrobial drugs for the treatment of neonatal pertussis and the antigen genotypes of Bordetella pertussis (B. pertussis) strains. Methods A total of 32 B. pertussis strains isolated from neonates between May 2013 and July 2018 were used in this study. E-test stripes were used to measure the minimal inhibitory concentration (MIC) of 18 antimicrobial drugs including erythromycin, sulfamethoxazole-trimethoprim (SMZ) and ampicillin. The 23S rRNA gene of isolated strains was amplifed and sequenced to identify the mutation site of erythromycin resistance gene, and the seven antigen genotypes of B. pertussis strains (ptxA, ptxC, ptxP, prn, fm2, fm3 and tcfA2) were analyzed. Results Of the 32 B. pertussis strains, 25 (78%) were resistant to erythromycin, azithromycin, clarithromycin and clindamycin, with an MIC of >256 mg/L, and A2047G mutation was observed in the 23S rRNA gene. All strains had an MIC of ≤ 0.064 mg/L for SMZ. The MIC of ampicillin, amoxicillin, amoxicillinclavulanic acid and ceftriaxone ranged from 0.032 to 1 mg/L. The strains resistant to macrolide antibiotics had an antigen genotype of ptxA1/ptxC1/ptxP1/prn1/fm2-1/fm3-1/tcfA2. Conclusions B. pertussis strains from neonates are often resistant to macrolides, and the in vitro test shows that off-label use of sulfonamides is a reliable regimen for the treatment of neonates with macrolide-resistant pertussis. The prevalence of drug-resistant strains further emphasizes the importance of immunoprophylaxis.

Objective To study the clinical features of children with acute disseminated encephalomyelitis (ADEM) and related recurrence factors. Methods A retrospective analysis was performed for the clinical data and prognosis of 73 children with ADEM who were hospitalized from November 2011 to January 2017. Results Among the 73 children, 41 (56%) had a history of infection before onset and 7 (10%) had a history of vaccination. All children had the symptoms of encephalopathy, including disturbance of consciousness in 47 children (64%) and mental and behavioral disorders in 54 children (74%). Pyrexia was observed in 53 children (73%), dyskinesia in 47 children (64%), headache in 47 children (64%) and vomiting in 40 children (55%). Brain MRI was performed for 65 children and the results showed involvement of the subcortical white matter (83%, 54/65), the deep nuclei (60%, 39/65), the brain stem (58%, 38/65) and the cerebellum (42%, 27/65). Spinal cord involvement was observed in 20 children (20/43, 47%). A total of 15 children experienced recurrence during follow-up. Compared with the non-recurrence group, the recurrence group had signifcantly higher percentages of children with deep nucleus involvement (P < 0.05), with injury in ≥ 3 spinal segments (P < 0.01) and with a time from disease onset to gamma-globulin/hormone treatment of >2 weeks (P < 0.05). Conclusions ADEM in children have various clinical manifestations. A small number of children may experience recurrence. Deep nucleus involvement on MRI, long spinal segmental injury (≥ 3 segments) and late treatment with gamma-globulin/hormone (>2 weeks) may be associated with the recurrence of ADEM.

Objective To study the clinical effect of psychological and behavioral intervention combined with biofeedback in the treatment of preschool children with attention deficit hyperactivity disorder (ADHD). Methods Sixty children each with inattentive, hyperactive/impulsive or combined type ADHD were enrolled. According to the intervention measure, they were randomly divided into 4 groups:control, psychological and behavioral intervention, biofeedback treatment and comprehensive treatment (psychological and behavioral intervention + biofeedback). Attention concentration time and impulse/hyperactivity and hyperactivity index scores of the Conners Parent Symptom Questionnaire (PSQ) were evaluated after 4 months of treatment. Results The attention concentration time increased in all types children with ADHD after psychological and behavioral intervention, biofeedback treatment or comprehensive treatment (P < 0.05). In children with inattentive ADHD, hyperactive/impulsive ADHD or combined-type ADHD, biofeedback or comprehensive treatment reduced the impulse/hyperactivity index score (P < 0.05). In children with inattentive or combined-type ADHD, psychological and behavioral intervention or comprehensive treatment reduced the hyperactivity index score (P < 0.05). In children with hyperactive/impulsive ADHD, biofeedback treatment, psychological and behavioral intervention or comprehensive treatment reduced the hyperactivity index score (P < 0.05). Conclusions In children with ADHD, psychological and behavioral intervention combined with biofeedback treatment can improve the attention concentration and impulsive/hyperactive and hyperactive symptoms. The treatment strategies are slightly different for children with different types of ADHD.

Objective To study the clinical effect of integrated sandplay therapy in preschool children with Asperger syndrome (AS). Methods A total of 44 preschool children with AS were randomly divided into an experimental group and a control group, with 22 children in each group. The children in the control group were given routine training, and those in the experimental group were given integrated sandplay therapy in addition to the routine training. The treatment response was assess by the Social Responsiveness Scale (SRS), emotional recognition tools and changes in sandplay theme characteristics after 6 months of treatment. Results Before intervention, there were no signifcant differences between the two groups in the total score of SRS, the score of each factor of SRS, and correct rates of facial expression recognition of the upright position, inverted position, upper face and lower face (P > 0.05). After 6 months of intervention, both groups had signifcant reductions in the total score of SRS and the score of each factor of SRS (P < 0.01); the control group had signifcant increases in the correct rates of facial expression recognition of all positions except the upright position (P < 0.05), while the experimental group had significant increases in the correct rates of facial expression recognition of all positions (P < 0.05). Compared with the control group after intervention, the experimental group had significantly lower total score of SRS and scores of all factors of SRS except social perception (P < 0.01) and signifcantly higher correct rates of facial expression recognition of all positions (P < 0.01). The experimental group had a signifcant change in the number of sandplay theme characteristics after intervention (P < 0.01). Conclusions Integrated sandplay therapy can improve social responsiveness and emotion recognition ability in preschool children with AS.

Objective To study the association of copy number of SMN1 and SMN2 with clinical phenotypes in children with spinal muscular atrophy (SMA). Methods A total of 45 children with SMA were enrolled. Multiplex ligation-dependent probe amplifcation was used to measure the gene copy numbers of SMN1 and SMN2. The association of copy number of SMN1 and SMN2 with clinical phenotypes was analyzed. Results Of the 45 children with SMA, 42 (93%) had a homozygous deletion of SMN1 exons 7 and 8, and 3 (7%) had a deletion of SMN1 exon 7 alone. No association was found between SMA clinical types and the deletion types of SMN1 exons 7 and 8 (P > 0.05). There was a signifcant difference in the distribution of SMN2 gene copy numbers between the children with SMA and the healthy children (P < 0.05). The children with SMA usually had two or three copies of SMN2 gene, while the healthy children usually had one or two copies of SMN2 gene. There was a significant difference in the distribution of SMN2 copy numbers among the children with different SMA clinical types (P < 0.05). The children with two copies of SMN2 gene had a signifcantly lower age of onset than those with three or four copies. Most of the children with type I SMA had two or three copies of SMN2 gene. Most of the children with type Ⅱ SMA had three copies of SMN2 gene. Most of the children with type Ⅲ SMA had three or four copies of SMN2 gene. Children with a higher copy number of SMN2 gene tended to have an older age of onset and better motor function and clinical outcome, and there was a signifcant association between SMN2 gene copy number and clinical outcome (P < 0.05). Conclusions The SMN2 gene can reduce the severity of SMA via the dosage compensation effect. SMN2 copy number is associated with the phenotype of SMA, and therefore, it can be used to predict disease severity.

Objective To investigate the incidence of neonatal birth trauma in the department of obstetrics in a single-center medical institution and the risk factors for neonatal birth trauma. Methods The maternal and infant medical records of all full-term singleton neonates delivered in the Department of Obstetrics, Peking University International Hospital, from October 2015 to September 2018 were collected. The neonates with birth trauma were assigned to case group, and those without birth trauma were assigned to control group. The risk factors for neonatal birth trauma were identified by multivariate logistic regression analysis. Results Of the 4 682 full-term singleton neonates delivered during the study period, 201 (4.29%) were diagnosed with birth trauma. The most frequent type of birth trauma was cephalohematoma (81.7%), followed by facial nerve palsy (9.1%). The multivariate logistic regression analysis identified vaginal delivery, forceps-assisted delivery, induction of labor by oxytocin, premature rupture of membranes and a large neonatal head circumference as the risk factors for birth trauma (OR=5.020, 23.294, 1.409, 1.928 and 2.295 respectively; P < 0.05). Conclusions The most frequent type of neonatal birth trauma is cephalohematoma. Vaginal delivery, forceps-assisted delivery, induction of labor by oxytocin, premature rupture of membranes and a large neonatal head circumference may increase the risk of neonatal birth trauma, and forceps-assisted delivery is the strongest independent risk factor for birth trauma.

Objective To study the clinical features, etiology and prognosis of neonates with nonimmune hydrops fetalis (NIHF). Methods A retrospective analysis was performed for the clinical data and outcomes of 23 neonates with NIHF. Results Of the 23 neonates with NIHF, 18 (78%) were preterm infants and 5 (22%) were full-term infants; 12 (52%) had birth asphyxia (including 5 cases of severe asphyxia). As for the causes of NIHF, 8 neonates (35%) had twintwin transfusion syndrome (TTTS), 3 (13%) had cardiovascular malformation, 3 (13%) had parvovirus B19 infection, 2 (9%) had congenital chylothorax, 1 (4%) had Turner syndrome, 1 (4%) had Coxsackie virus infection, and 5 (22%) had unknown etiology. Of the 23 neonates, 13 achieved clinical cure, 10 died, resulting in a neonatal mortality rate of 43%. Compared with the survival group, the death group had a signifcantly higher proportion of preterm infants or infants with asphyxia, 5-minute Apgar score <8 or heart failure (100%/100%/60%/60% vs 62%/15%/8%/8%; P < 0.05). Conclusions Birth asphyxia is common in neonates with NIHF. The neonates with a lower gestational age, a more serious asphyxia or heart failure have a higher risk of death in the neonatal period. Being the recipient of TTTS is a major cause of NIHF.

Objective To study the features of serum metabolites in preterm infants based on gas chromatographymass spectrometry (GC-MS), and to find differentially expressed metabolites in the serum of preterm infants. Methods Serum samples were collected from 19 preterm infants and 20 full-term infants before feeding. GC-MS was used to measure metabolic profles, and the metabolic features of 397 serum metabolites in preterm infants were analyzed. Results There was a signifcant difference in serum metabolic features between the preterm and full-term infants before feeding. There were significant differences between the full-term and preterm infants in the levels of metabolites such as O-phosphonothreonine, digicitrin, tannic acid, and fructose-1,6-diphosphate (P < 0.01), suggesting that the above differentially expressed metabolites were highly differentiated between the preterm and full-term infants. Most differentially expressed metabolites were involved in the metabolic pathways such as ABC transporters, β-alanine and pyrimidines and were correlated with some clinical parameters (albumin and total bilirubin) (P < 0.05). Conclusions There is a significant difference in serum metabolites between preterm and full-term infants before feeding. Metabolomics plays an important role in improving metabolic disorders and exploring metabolism-related diseases in preterm infants.

Objective To study the clinical effect and safety of tacrolimus (TAC) combined with glucocorticoid (GC) versus mycophenolate mofetil (MMF) combined with GC in the treatment of primary IgA nephropathy (IgAN) in children. Methods A retrospective analysis was performed for the clinical data of children with primary IgAN confrmed by renal pathology between January 2012 and December 2017. These children were divided into TAC group and MMF group according to the treatment regimen. Their clinical data before treatment and at 1, 3, and 6 months of treatment were collected, and the remission status of IgAN and adverse reactions were compared between the two groups. Results A total of 43 children who met the inclusion criteria were enrolled, with 15 children in the TAC group and 28 children in the MMF group. At 1 month of treatment, there was no signifcant difference in the remission status between the two groups (P > 0.05). At 3 and 6 months of treatment, the TAC group had a signifcantly better remission status than the MMF group (P < 0.05). At 1 month of treatment, the TAC group had higher serum albumin levels than the MMF group (P < 0.05). Both groups had a signifcant increase in serum albumin levels at each time point after treatment (P < 0.0083) and a signifcant increase in the glomerular fltration rate (GFR) at 3 and 6 months of treatment (P < 0.0083). There was no signifcant difference in the overall incidence rate of adverse reactions between the two groups (P > 0.05), but fungal infection was observed in one child from the TAC group. Conclusions TAC combined with GC can effectively reduce urinary protein in children with primary IgAN, and it has a better short-term clinical effect than MMF combined with GC, with good safety.

Objective To investigate the epidemiological and clinical features of cow's milk protein allergy (CMPA) in infants presenting mainly with gastrointestinal symptoms. Methods A retrospective analysis was performed for the clinical data of 280 hospitalized infants, who were diagnosed with CMPA presenting mainly with gastrointestinal symptoms. Results Among the 280 infants, 203 infants(72.5%) were aged of less than 6 months. Major manifestations included diarrhea in 171 infants (61.1%), hematochezia in 149 infants (53.2%), vomiting in 71 infants (25.4%), eczema in 57 infants (20.4%), malnutrition in 42 infants (15%) and constipation in 13 infants (4.6%). Of the 280 infants, 258 (92.1%) had mild-to-moderate CMPA and 22 (7.9%) had severe CMPA. Compared with the mild-to-moderate CMPA group, the severe CMPA group had a significantly higher incidence rate of malnutrition (50.0% vs 12.0%) and a signifcantly lower incidence rate of hematochezia (22.7% vs 55.8%). The breastfeeding CMPA group had signifcantly lower incidence rates of malnutrition (10.3% vs 24.6%) and severe CMPA (4.4% vs 18.0%) than the artifcial feeding CMPA group, and the artifcial feeding CMPA group had a signifcantly lower incidence rate of hematochezia than the breastfeeding and mixed feeding CMPA groups (37.7% vs 56.6%/59.0%). Conclusions CMPA presenting mainly with gastrointestinal symptoms is more common in infants aged of less than 6 months. Diarrhea and hematochezia are the most common manifestations at the time of onset. Most infants have mild-to-moderate allergy. Compared with breastfeeding, artifcial feeding is more likely to cause malnutrition and severe CMPA.

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Objective To study the role of miR-431 in lung development and morphology. Methods According to the stage of lung development in rats, Sprague-Dawley rats at embryonic day 16 (E16), embryonic day (E19), embryonic day (E21), postnatal day 1 (P1), postnatal day 3 (P3), postnatal day 7 (P7), postnatal day 14 (P14) and 10 weeks after birth (P10 weeks) were selected, and lung tissue samples were collected for observation. Hematoxylin-eosin staining and transmission electron microscopy were performed to observe the morphology of lung tissue. Fluorescence in situ hybridization and real-time PCR were used to measure the expression of miR-431 during the critical stages of lung development (E19, E21 and P3). Results The E19 group had the formation of the lamellar body and type Ⅱ alveolar epithelial cells in the fetal lung tissue. The number of lamellar bodies increased with the increasing gestational age, with aggregation and excretion. Pulmonary alveoli formed rapidly, the lung interstitium became thinner, and the microvascular system became mature after birth. Fluorescence in situ hybridization and real-time PCR showed that the expression of miR-431 gradually decreased with the increasing gestational age (P < 0.05). Conclusions The systematic and continuous morphological data of lung development is obtained in this experiment. In addition, miR-431 may play an important role in the negative regulation of lung development, which provides basis and direction for further research on the mechanism of lung development and related diseases.

Objective To study the effects of respiratory syncytial virus (RSV) infection on epidermal growth factor receptor (EGFR), tight junction association proteins and mucin in the human airway epithelial cells. Methods Human airway epithelial cells NCI-H292 were randomly treated by ultraviolet light-inactivated RSV (control group) or thawed RSV (RSV infection group). After 48 hours of treatment, the protein levels of occludin, E-cadherin, phosphorylated EGFR and EGFR in NCI-H292 cells were measured by Western blot. The distribution and expression levels of occludin and E-cadherin in NCI-H292 cells were examined by immunofluorescence technique. The expression levels of MUC5AC mRNA in NCI-H292 cells were assessed by RT-PCR. Results The protein levels of occludin and E-cadherin were signifcantly reduced in the RSV infection group compared with the control group (P < 0.05). The protein levels of phosphorylated EGFR and EGFR increased signifcantly in the RSV infection group compared with the control group (P < 0.05). The MUC5AC mRNA levels also increased signifcantly in the RSV infection group compared with the control group (P < 0.05). Conclusions RSV may down-regulate the tight junction association proteins and upregulate the expression of MUC5AC in airway epithelial cells, which contributes to epithelial barrier dysfunction. EGFR phosphorylation may play an important role in regulation of airway barrier.

Objective To study the methylation level and dynamic change of 5-hydroxymethylcytosine (5hmC) in mitochondrial DNA (mtDNA) in the cerebral cortex of neonatal rats with hypoxic-ischemic brain damage. Methods A total of 24 male Sprague-Dawley rats aged 7 days were randomly divided into control group, 24-hour model group and 48-hour model group (n=8 each). Common carotid artery ligation combined with hypoxic treatment was performed to establish an animal model of hypoxic-ischemic brain damage. The rats in the control group were not given ligation or hypoxic treatment. Oxidative bisulfte sequencing was used to measure the level of 5hmC in the cerebral cortex. Western blot was used to measure the expression of 5hmC-related enzymes TET1, TET2 and DNMT1. Results The 24- and 48-hour model groups had a signifcantly higher level of 5hmC than the control group (P < 0.05). Western blot showed a signifcant increase in the expression of DNMT1 in the 24- and 48-hour model groups (P < 0.05). Compared with the control group, the 24- and 48-hour model groups had signifcant differences in the 5hmC level at multiple mitochondrial genetic loci (P < 0.05). Conclusions The level of DNMT1, a key enzyme for 5hmC modifcation in mtDNA, in the cerebral cortex increases in neonatal rats with hypoxic-ischemic brain damage, suggesting that there is an abnormal methylation level of 5hmC after hypoxic-ischemic brain damage, which might be associated with the regulation of hypoxic-ischemic brain damage.