There is uniformed definition of rare diseases in children, which can be viewed as rare diseases that develop in childhood, or the childhood of patients with rare diseases. Rare diseases are rarely seen in clinical setting, various in types and difficult to diagnose and treat. In the past few years, with the rapid development of medical technology and the establishment and wide application of rare disease management systems, great progress has been made in the diagnosis and treatment of rare diseases. Although the management of rare diseases is being gradually expanded and enhanced, there are still challenges, or opportunities for further improvement. China is a vast country with imbalanced distribution of medical resources. In many places, people have limited knowledge about the pathogenesis of many rare diseases. Capacities vary in the detection, diagnosis, and treatment of rare disease in different places. As a result, most rare diseases are either misdiagnosed or not diagnosed at all. Therefore, it is of great significance to establish a hierarchical system for the management of rare diseases, i.e., appropriate triage, risk stratification, early diagnosis and scientific treatment, and integrate regional resources into rare disease management. Studies have confirmed the existance of heterogeneity of rare diseases, with more than half of them occurring at birth or in childhood and that they are associated with a high mortality rate and a high incidence of functional disabilities in survivors. Therefore, rare diseases in child-ren deserve more attention. Standardized, protocol-based, law-based management of rare diseases in children is in urgent need. The article aims to discuss the status quo of the management of rare diseases in children, to summarize the clinical progress of rare diseases in children and to explore its prospects in the future, in the hope to provide some reference for the management of rare diseases in children.

Objective:To evaluate the effect of PACS system (picture archiving and communication system) in the standardized residency training of cardiovascular medicine.Methods:Fifty-nine residents taking the standardized residency training of cardiovascular medicine in Changhai Hospital from 2018 to 2019 were randomly divided into PACS teaching group ( n = 30) and traditional teaching group ( n = 29). The research group adopted the PACS system for the teaching of cardiovascular medicine, and the control group took the traditional teaching method. The teaching effect was evaluated by theoretical examination, imaging examination and questionnaire. SPSS 19.0 was used for t test and chi-square test. Results:The theoretical and film reading scores of the PACS teaching group were significantly higher than those of the control group [(87.70 ± 6.52) vs. (80.55 ± 8.63); (86.67 ± 6.33) vs. (77.48 ± 10.29), P < 0.05)]. The results of the questionnaire showed that PACS teaching method was helpful for residents to master cardiovascular knowledge, arouse their learning interest and improve their clinical thinking ability. The satisfaction with the teaching method in the PACS teaching group was significantly higher than that in the traditional teaching group [(9.22 ± 0.44) vs. (8.26 ± 0.72), P < 0.05]. Conclusion:The application of PACS system in the teaching of cardiovascular medicine can significantly improve the teaching effect of residents.

Objective:To explore the strategies and complications of the submucosal tunneling endoscopic resection (STER) in the treatment of esophageal duplicated cyst (EDC).Methods:From January 2013 to December 2019, at Department of Gastroenterology, Taizhou Hospital of Zhejiang Province, the clinical data of 11 hospitalized patients with EDC diagnosed by pathological examination who underwent STER were collected. The clinical featured, computed tomography (CT) findings, endoscopic findings, postoperative efficacy, complications and pathological results after operation were summarized.Results:Among the 11 patients, there were 6 males and 5 females, the age ranged from 13 to 67 years, and the mean age was (43.0±18.2) years. One case presented with swallowing obstruction, 1 case with belching, 4 cases with upper abdominal pain, and the remaining 5 cases had no specific clinical symptoms. Under endoscopy, the lesions of 11 patients were hemispherical or mound-shaped with smooth surface submucosal masses in the esophageal cavity, which were soft to touch. Under endoscopic ultrasonography, they all appeared as hypoechoic masses with clear boundary located in the esophageal muscularis propria. The results of CT scan of 9 patients showed round low-density cystic masses, among them 7 cases showed mild enhancement. The maximum diameter of the cysts was 1.5 to 4.4 cm, with mean maximum diameter being (2.8±0.8) cm, and the maximum diameter of most patients (7 cases) were 2 to 3 cm. The other two patients showed only slightly thickened esophageal wall on CT. Five lesions occurred in the horizontal mediastinum of the lower esophagus. All the 11 patients underwent STER operation successfully, among them 6 patients received simple STER and the cysts were completely resected, and the other 5 patients received STER and cauterization with argon ion for the residual cyst wall. The pathological results after operation indicated that 6 cases were congenital esophageal cysts and 5 cases were bronchogenic cysts. The median follow-up time (range) of 11 patients was 42 months (12-86 months). Ten patients recovered well after the operation, and local recurrence, malignant transformation or metastasis were not found. One case had recurrence, and was treated with STER and cauterization with argon ion for residual cyst wall and cured. No complications such as bleeding, fistula, mediastinal infection or death occurred during and after operation in all the 11 patients.Conclusions:STER is a minimally invasive, safe and effective treatment for EDC, and may be a new treatment for EDC.

Objective:To analyze the pathogenic bacteria and epidemiological characteristics in children with respiratory tract infection in Tianjin area.Methods:Retrospective case analysis was performed on 2 392 hospitalized children in the wards of respiratory diseases, intensive care unit and special care ward of Tianjin Children′s Hospital from June 2018 to May 2019. Thirteen pathogenic bacteria in deep sputum and bronchoalveolar lavage fluid samples were detected by loop-mediated isothermal amplification. The laboratory data and clinical characteristics of the infected children were analyzed, and the comparison between groups was performed by t test or χ 2 test. Results:Among 2 392 cases, 1 407 were males and 985 females. There was no significant difference in the detection rate between males and females (72.5% (1 020/1 407) vs.74.2% (731/985), χ 2=0.87, P=0.35). A total of 1 751 strains and 12 kinds of positive respiratory pathogens were detected, with a detection rate of 73.2%. Among them, 913 (38.2%) strains were Mycoplasma pneumoniae (MP), 514 (21.5%) were Streptococcus pneumoniae (Sp), 381 (15.9%) were Methicillin-resistant Staphylococcus aureus (MRSA) and 279 (11.7%) were Hemophilus influenzae (Hi). There was significant difference in the detection rate of pathogens among different age groups (χ2=83.67, P<0.01). The positive rate of alveolar lavage fluid group was higher than that of deep sputum fluid group [81.6% (614/752) vs. 69.3% (1 137/1 640), χ 2=39.89, P<0.01]. The length of hospital stay of children infected with different pathogens was significantly different (all P<0.01). There was significant difference in duration of fever among children infected with different pathogens (χ2=228.69,103.56, 3.96, 27.38,24.50,41.66, all P<0.05). There were 63 (7.7%) cases of atelectasis, 260 (31.9%) cases of pleurisy and 120 (14.7%) cases of pleural effusion in MP children. Children with Sma were most likely to involve the heart system (2/9), and children with Eco infection had a higher incidence of complications such as those of blood (3/19), urinary (2/19), digestive systems(4/19), systemic inflammatory response syndrome and sepsis (1/19). Conclusions:The main bacterial pathogens of respiratory tract infection in children in Tianjin were MP, Sp, MRSA and Hi. It is suggested that clinicians should not only pay attention to the respiratory symptoms of children, but also pay attention to the complications caused by bacterial pathogen infection, so as to prevent the deterioration of the disease and improve the prognosis.

Objective: To explore the correlation between sleep and the severity of coronary artery stenosis, and to further guide the prevention and control of coronary heart disease. Methods: A total of 302 patients, including 183 males and 119 females, were enrolled in the department of cardiology of Changhai hospital from February to June 2019. The patients were divided into three groups according to the degree of stenosis (atherosclerotic group, atherosclerotic group with degree of stenosis <50%, atherosclerotic group with degree of stenosis 50%-70%, and atherosclerotic group with degree of stenosis >70%). General information, comorbidities and Pittsburgh sleep quality index (PSQI) of patients in each group were analyzed to compare the differences and analyze the risk factors of aggravated coronary artery stenosis. Results: There were statistically significant differences in age, gender and diabetes among all groups (P<0.05). There was no statistically significant difference in the incidence of hypertension and hyperlipidemia in each group (P>0.05). Spearman correlation analysis showed that PSQI score was positively correlated with the degree of atherosclerosis (P<0.01). In the multivariate regression model, poorer sleep quality (OR=1.75, 95% CI: 1.14-2.69, P<0.05), shorter sleep time (OR=1.64, 95% CI: 1.05-2.55, P<0.05) and more diurnal dysfunction (OR=1.45, 95% CI: 1.11-1.88, P<0.01) were correlated with increased coronary artery stenosis. Higher PSQI total score (OR=1.13, 95% CI: 1.06-1.20, P<0.01) and lower PSQI evaluation grade (very bad vs very good: 13.85, 95% CI: 1.56-122.82, P<0.05) were also related to the increase of coronary artery stenosis. Conclusions Poorer sleep quality, shorter sleep time and more diurnal dysfunction were independent risk factors for the aggravation of coronary artery stenosis. Higher Pittsburgh sleep quality index was significantly associated with the severity of coronary artery stenosis.

Objective: To investigate the clinical significance of detection of urine renal injury biomarkers in children with primary nephrotic syndrome (PNS). Methods: Seventy-nine children with PNS at the Department of Nephrology, Tianjin Children′s Hospital were enrolled from January to December 2016, who were given sufficient glucocorticoid for 4 weeks.According to the response to glucocorticoid, they were divided into steroid-sensitive nephrotic syndrome (SSNS) group (63 cases) and steroid-resistant nephrotic syndrome (SRNS) group (16 cases), then they were divided into simple type and nephritic type according to diagnostic criteria.Urinary levels of microalbuminuria (MAlb), transferrin (TfR), retinal binding protein (RBP), N-acetyl-β-D-glucosaminidase (NAG), α1-microglobulin (α1-MG) and β₂-microglobulin (β₂-MG) were measured in the children before and after treatment, and the data were analyzed by the statistical method. Results: Before treatment, the levels of RBP, NAG, α1-MG and β₂-MG in the SSNS group [0.91(1.80) mg/L, 28.00(31.5) U/L, 8.40(14.2) mg/L, 0.45(0.35) mg/L]were lower than those in SRNS group[3.94(4.82) mg/L, 37.10(18.20) U/L, 11.10(21.42) mg/L, 0.66(1.41) mg/L], and the differences were statistically significant (all P<0.05); After treatment, the MAlb, TfR, RBP, NAG, α1-MG, β₂-MG in the SSNS group [14.10(5.60) mg/L, 0.40(1.60) mg/L, 0.26(0.38) mg/L, 7.90(9.10) U/L, 2.00(4.40) mg/L, 0.27(0.35) mg/L] were lower than those before treatment[MAlb: 1 704.00(1 995.60) mg/L, TfR: 142.10(81.90) mg/L] and those after treatment in the SRNS group[557.90(1 857.17) mg/L, 117.40(102.10) mg/L, 4.19(5.15) mg/L, 38.80(32.43) U/L, 10.85(16.60) mg/L, 0.63(0.91) mg/L], and the differences were statistically significant (all P<0.05). However, before and after treatment, except for MAlb[before treatment: 2 258.75(2 028.43) mg/L], the indicators in the SRNS group were not significantly improved.Before treatment, the RBP in the SRNS group was significantly higher than that in the SSNS group in children with simple type PNS, and the RBP, NAG, α1-MG and β₂-MG in the SRNS group were significantly higher than those in the SSNS group in children with nephritic type PNS (all P<0.05). According to receiver operating characteristic curve, there were obvious differences in the urinary levels of RBP, NAG and β₂-MG, and area under curve(AUC) was 0.858, 0.837 and 0.679, respectively, all of which were <0.9, so the value of diagnosis was not high.Logistic regression analysis was used to identify RBP and NAG as influencing factors and to establish a model.Through the combined detection of these two indicators, the diagnostic value was higher (AUC was 0.956), and when the diagnostic sensitivity was 93.8%, the specificity could reach 82.5%. Conclusions Urinary RBP, NAG, α1-MG and β₂-MG can early reflect tubular interstitial impairment in children with PNS, especially SRNS.Combined detection of RBP and NAG has certain value in predicting the efficacy of glucocorticoid.

Objective: To investigate the drug resistance and risk factors of community-acquired urinary tract infection(UTI) caused by extended-spectrum β-lactamase(ESBLs)-producing Escherichia coli in children. Methods: The clinical data of 125 children with community-acquired urinary tract infection caused by Escherichia coli were analyzed, who were hospitalized at Department of Pediatric Nephrology of Tianjin Children′s Hospital from June 2017 to June 2018.The ESBLs-producing group and the non ESBLs-producing group were named depending on the production of the ESBLs.WHONET 5.6 bacterial resistance monitoring software was used to calculate the drug resistance rate of bacteria.The drug resistance rate and clinical data were analyzed by adopting χ² test and Fisher′s exact probability method, then, factors with statistical significance identified by single factor analysis were further analyzed by multivariate Logistic regression analysis. Results: Among 125 strains of Escherichia coli, 68 strains(54.4%) were ESBLs-producing Escherichia coli and 57 strains(45.6%) were non ESBLs-producing.The drug resistance rates of ESBLs-producing Escherichia coli to penicillins, cephalosporins, quinolones and monocyclic beta-lactams were higher than those of non ESBLs-producing strains, and the drug resistance rates to Ampicillin, Piperacillin, Cefazolin, Cefuroxime, Ceftriaxone and Cefotaxime were nearly 100%.The resistance rates of ESBLs-producing strains to Imipenem, Meropenem, Amikacin, Furantoin, Cefotetan and Piperacillin/Tazobactam were lower (< 5%). Univariate analysis showed that there were significant differences in recurrent UTI (χ²=12.043, P<0.01) and use of third-generation cephalosporins in the past 3 months(χ²=28.545, P<0.01) between ESBLs-producing group and non ESBLs-producing group.Multivariate Logistic regression analysis showed that use of third-generation cephalosporins in the past 3 months was an independent risk factor of community-acquired UTI caused by ESBLs-producing Escherichia coli(OR=11.285, 95%CI: 3.140-39.134, Wald=13.972, P<0.01). Conclusions The isolation rate of ESBLs-producing Escherichia coli in children with community-acquired UTI is high, and the drug resistance rate is high, so children who used third-generation cephalosporins in the past 3 months were more likely to develop community-acquired UTI caused by ESBLs-producing Escherichia coli.

Objective To explore the pathologic features and distribution characteristics of upper gastrointestinal submucosal tumors (SMT).Methods From January 2013 to December 2017,at Department of Gastroenterology of Taizhou Hospital Affiliated to Wenzhou Medical University,clinical data of 1 182 hospitalized patients with 1 237 upper gastrointestinal SMT who underwent endoscopic therapy and diagnosed by pathology and immunohistochemistry was retrospectively analyzed including the pathological types,tumor of locations,endoscopic findings,layer of origin and tumor size.Results There were 473 esophageal SMT,including 387(81.8％) leiomyomas,located in the mucosal muscularis or muscularis propria;and 59(12.5％)cysts located in the submucosa or mucosal muscularis.There were 138(29.2％) lesions,159(33.6％) lesions and 176(37.2％) lesions in the upper,middle and lower esophagus respectively,and the most common type was leiomyoma.A total of 723 tumors were gastric SMT,among them 284 (39.3％) lesions were gastrointestinal stromal tumors (GIST) and 273(37.8％) lesions were leiomyomas,and all located in the muscularis propria.A total of 69(9.5％) lesions located at cardia,the common types were leiomyoma (55 lesions,79.7％) and GIST (nine lesions,13.0％).A total of 239 (33.1％) lesions located at gastric fundus,the common types were GIST (152 lesions,63.6％) and leiomyoma (79 lesions,33.1％).A total of 280 (38.7％) lesions located at gastric body,the common types were leiomyoma (138 lesions,49.3％) and GIST (111 lesions,39.6％).A total of 127 (17.6％) lesions located at gastric antrum,the common types were heterotopic pancrease (71 lesions,55.9％) and lipoma (26 lesions,20.5％),and all were located in the submucosa,some involved the muscularis propria.There were six (0.8％) lesions at gastric angle,and two (0.3％) at gastrointestinal anastomosis.Forty-one lesions were duodenal SMT,among them 23(56.1％) located at duodenal bulb,the common types were cyst (10 lesions,43.5％),lipoma (five lesions,21.7％) and heterotopic pancrease (five lesions,21.7％).A total of 18(43.9％) lesions located at descending duodenum,the common types were lipoma (nine lesions,50.0％) and cyst (five lesions,27.8％),and all lesions located in the submucosa.Conclusions The most common type of SMT in the esophagus and cardia is leiomyoma,however the SMT in gastric fundus and body are mostly leiomyomas and GIST,while in gastric antrum,most SMT are heterotopic pancreases and lipomas.In duodenal bulb and descending duodenum,the common types of SMT are cyst and lipoma.

Objective: To establish comprehensive laboratory reference intervals for Chinese children. Methods: This was a cross-sectional multicenter study. From June 2013 to December 2014, eligible healthy children aged from 6-month to 17-year were enrolled from 20 medical centers with informed consent. They were assessed by physical examination, questionnaire survey and abdominal ultrasound for eligibility. Fasting blood samples were collected and delivered to central laboratory. Measurements of 15 clinical laboratory parameters were performed, including estradiol (E2), testosterone(T), luteinizing hormone(LH), follicle-stimulating hormone(FSH), alanine transaminase(ALT), serum creatinine(Scr), cystatin C, immunoglobulin A(IgA), immunoglobulin G(IgG), immunoglobulin M(IgM), complement (C3, C4), alkaline phosphatase(ALP), uric acid(UA) and creatine kinase(CK). Reference intervals were established according to central 95% confidence intervals for reference population, stratified by age and sex. Results: In total, 2 259 children were enrolled. Finally, 1 648 children were eligible for this study, including 830 boys and 818 girls, at a mean age of 7.4 years. Age- and sex- specific reference intervals have been established for the parameters. Reference intervals of sex hormones increased gradually with age. Concentrations of ALT, cystatin C, ALP and CK were higher in children under 2 years old. Serum levels of sex hormones, creatinine, immunoglobin, CK, ALP and urea increased rapidly in adolescence, with significant sex difference. In addition, reference intervals were variable depending on assay methods. Concentrations of ALT detected by reagents with pyridoxal 5'-phosphate(PLP) were higher than those detected by reagents without PLP. Compared with enzymatic method, Jaffe assay always got higher results of serum creatinine, especially in children younger than 9 years old. Conclusion This study established age- and sex- specific reference intervals, for 15 clinical laboratory parameters based on defined healthy children.

Objective To investigate the distribution and antibiotic resistance to pathogens isolated from children with acute pyelonephritis(APN) and explore the risk factors for it.Methods A retrospective analysis was performed on the distribution and antibiotic resistance to 173 pathogens isolated from 264 children with APN who hospitalized at Tianjin Children's Hospital from March 2012 to March 2017.The antibiotic resistance to pathogens was determined by using antimicrobial susceptibility.The clinical indicators of children were compared with APN and 200 children with lower urinary tract infection,including sex,age,index of blood and urine.The risk factors for APN were analyzed.Results Gram-negative bacilli were the main pathogen (61.3％),and involved Escherichia coil (E.coil) of 34.1％.Gram-positive cocci accounted for 38.7％,and involved enterococcus faecium of 24.3％.The resistance rate of E.coli to Ampicillin was the highest(89.8％),but the rate significantly decreased by adding Amoxicillin/Clavulanic acid(47.5％).Compared with Ampicillin,the difference was statistically significant(P ＜ 0.05).The resistance rate of E.coli to Tocefoperazone/Sulbactam was significantly lower than to other cephalosporins(P ＜ 0.01).E.coli had lowest resistance rate to Imipenem (0.03 ％).The resistance rate of enterococcus faecium was low to Linezolid and Vancomycin(＜ 5％).Single and multiple regression analysis revealed that younger than 1 year old,children with urinary tract malformation,increasing procalcitonin (PCT) of blood and β2-microglobulin (β2-MG) and neutrophil gelatinase-associated lipocalin (NGAL) of urine were all the risk factors of APN (all P ＜ 0.05).Conclusions E.coil is the major pathogen in children with APN and the enterococci-caused APN has been increasing.These pathogens have a high antibiotic resistance rate.Antimicrobial therapy should be based on the findings of urine culture and antimicrobial susceptibility test.In the children,less than 1 year old,with urinary tract malformation,the increasing PCT of blood,β2-MG and NGAL of urine are the risk factors for APN.