Cow′s milk protein allergy (CMPA) is one of the most common presentations of food allergy seen in early childhood.It is an abnormal immune response caused by cow′s milk protein.CMPA can be clinically subdivided into either immediate-onset IgE mediated or delayed onset non-IgE mediated, or both.At present, concerns regarding the early and timely diagnosis of CMPA have been high-lighted over the years and there are many expert consensus on CMPA in China, but these consensus did not distinguish IgE mediated or non-IgE mediated CMPA.In view of the obvious clinical differences between the two type of CMPA and non-IgE mediated CMPA is more common in infancy, experts focus on pediatric gastroenterology, allergy/immunology, dermatology, nutrition and child healthcare convened by the Allergy Prevention and Control Professional Committee of Chinese Preventive Medicine Association present this guideline to help practitioners in primary care settings to early recognize and make suitable management of non-IgE mediated CMPA in China.The guideline incorporates the cutting-edge international guidance and the actual situation of Chinese children describing in detail the types, clinical features, diagnosis and nutritional intervention of non-IgE mediated CMPA.There are 42 recommendations in 7 categories in total referring to the common questions related to non-IgE mediated CMPA.

Objective:To analyze the efficacy and safety of the biological agent infliximab (IFX) in the treatment of pediatric Crohn′s disease.Methods:A total of 86 children with Crohn′s disease who had received IFX in three hospitals (Ruijin Hospital, Ruijin Hospital North and Shanghai Children's Hospital) in Shanghai from January 2007 to December 2017 were included in this retrospective study. The efficacy of IFX was assessed by comparing clinical and laboratory data before and after IFX treatment. Student t test, Mann-Whitney U test or chi-square test were used to analyze the data of the two groups. Logistic reggression analysis were used to analyze the effects of variables such as age, clinical characteristics, disease behavior and combined medications on the efficacy and safety of IFX. Results:Among the 86 children with Crohn′s disease in the study, 50 were males and 36 females. The IFX treatment was initiated at 12.0 (7.1, 13.6) years of age, and the follow-up period was 94.1 (47.8, 185.5) weeks. Efficacy analysis showed that in the induction remission phase, the clinical response rate was 97% (79/81) and the remission rate was 74% (60/81). In the maintenance remission phase, the clinical response rate was 75% (51/68) and the remission rate was 68% (46/68). After 34 weeks of treatment with IFX, pediatric Crohn′s disease activity index (PCDAI) (5 (0, 10) vs. 36 (26, 45)), C-reactive protein (3 (1, 8) vs. 8 (3, 31) mg/L), erythrocyte sedimentation rate (10 (6, 10) vs. 35 (20, 50) mm/1 h), platelet ( (327±107)×10 9vs. (438±159) ×10 9/L), albumin ((37±6) vs. (30±6) g/L), hemoglobin ((116±16) vs. (103±18) g/L), change of body weight (-0.5±1.2 vs. -1.0±0.9), anemia (29% (20/68) vs. 75% (51/68)), and perianal disease (13/21 vs. 0) were significantly improved (all P<0.05). By the end of 34 weeks of IFX treatment, 25% (17/68) of children experienced secondary loss of response to IFX. Logistic reggression analysis showed that PCDAI>30 was positively correlated with secondary loss of response ( OR=3.823, 95% CI 1.015 -15.328, P=0.048), and combined with azathioprine was conducive to maintaining efficacy of IFX ( OR=0.440, 95% CI 0.106 -1.033, P=0.044). The IFX-related adverse events included infusion reactions in 17% (15/86) and infections in 42% (36/86) of children. Analysis showed that age<6 years was a risk factor for infusion reactions (χ 2=6.556, P=0.010), and combined use of steroids (χ 2=5.230, P=0.022) may increase the incidence of infection. Conclusions:IFX is effective in the treatment of pediatric Crohn′s disease with favorable safety. Reducing secondary loss of response to IFX is an urgent issue that need to be addressed. At the same time, it is necessary to pay close attention to the adverse events during IFX treatment.

Objective: To analyze the clinical characteristics of chronic pancreatitis (CP) and evaluate its impact on growth of children. Methods: A retrospective study was conducted in 94 children (male 49 cases, female 45 cases) who were diagnosed with CP in the Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from August 2008 to July 2015. Clinical characteristics, such as features of abdominal pain, etiologies, image data, levels of serum amylase and lipase, and physical development data were extracted from electronic medical records. The comparison between groups based on etiology or with normal control was performed with student′s t test. Results: The age of first episode was (8.2±3.7) years. There were 61 (65%) children diagnosed with idiopathic CP, and 25 (27%) with anatomic abnormalities. The age of onset in the group with anatomic abnormalities was lower than that in the idiopathic CP group ((6.3±3.5) vs. (8.9±3.4) years, t=3.211, P=0.002). There were 51 (54%) patients with serum amylase elevation, 41(44%) patients with lipase elevation, and 35 (37%) with elevation in both. The questionnaire showed that 28 out of 30 children had moderate to severe abdominal pain. The patients′ weight standard score (SDS) was significantly lower than the overall average in normal control (-0.4±1.1 vs. 0, t=-3.308, P=0.001). Meanwhile, the mean level of insulin like growth factor-1 (IGF-1) SDS of 35 children was significantly decreased (-1.8±1.8 vs. 0, t=-6.136, P<0.01). There were 69% (37/54) patients diagnosed by magnetic resonance cholangiopancreatography (MRCP) combined with magnetic resonance imaging (MRI), higher than that diagnosed by abdominal ultrasound (29%, 27/94). Conclusions Idiopathic CP and anatomic abnormalities were the two main etiologies. Normal level of serum amylase and lipase or negative finding of ultrasound cannot exclude CP, while MRCP and MRI should be considered to improve CP diagnostic rate. It is noteworthy that growth delay would happen in children with CP history.

Objective: To investigate the incidence and risk factors of extraintestinal manifestations (EIMs) in children with inflammatory bowel disease (IBD). Methods: The clinical data of 161 children with IBD was collected from the electronic medical records in the Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine from January 2012 to December 2017. These patients were divided into Crohn′s disease (CD) group and ulcerative colitis (UC) group, accounting for 82.0% (132 cases) and 18.0%(29 cases), respectively. The incidence of EIMs in each group was analyzed. The potential risk factors of EIMs including the IBD phenotype, gender, age, location of the CD lesion, disease activity of CD, and the presence of perianal lesion were analyzed with logistic regression model. Results: Eighty-eight patients (54.7%) had EIMs. The main EIMs were immune-mediated EIMs and growth retardation, accounting for 41.0% (66/161) and 24.2% (39/161), respectively. Aphthous ulcer (39/161, 23.0%) was the most common symptom among immune-mediated EIMs, followed by arthropathy (20/161, 12.4%) and skin lesions (19/161, 11.8%). Forty-three patients (26.7%) had EIMs before being diagnosed as IBD. Fifty-eight (65.9%) patients had only one EIM during the whole course of IBD. By logistic regression analysis, CD (OR=5.536, 95%CI:1.825-16.788) and perianal disease (OR=1.969, 95%CI:1.035-3.746) were the risk factors of immune-mediated EIMs. Meanwhile, CD (OR=11.319, 95%CI: 1.487-86.179), younger than six-year-old at diagnosis (OR=8.556, 95%CI: 3.109-23.545), moderate to severe activity of CD (OR=3.447, 95%CI: 1.196-9.934) and perianal disease (OR=3.361, 95%CI: 1.720-7.793) increased the risk of growth retardation. Conclusions The children with IBD have a high incidence of EIMs, which were more common in CD than in UC. The risk factors of developing EIMs include CD, perianal diseases, younger than six-year-old at diagnosis and moderate to severe activity of CD.

Objective To establish the quality standard of Wuji-Jianwei granules. Methods The contents of Bupleuri Radix, Codonopsis Radix, Paeoniae Radix Alba, Corydalis Rhizoma in Wuji-Jianwei granules were identified by using the thin layer chromatography (TLC) method. The contents of peoniflorin was determined by the high performance liquid chromatography (HPLC) method. Results The TLC had strong specificity and high separation, negative control without interference. The linear range was 0.124 8-0.748 8 μg for peoniflorin (r=0.999 6). The average recovery was 94.42% (RSD=1.46%) and the content of peoniflorin was 0.725 3 mg/g. Conclusions The method is accurate and reasonable, and can be used for the quality control of Wuji-Jianwei granules.

Objective To analyze the clinical characteristics of chronic pancreatitis (CP) and evaluate its impact on growth of children. Methods A retrospective study was conducted in 94 children (male 49 cases, female 45 cases) who were diagnosed with CP in the Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from August 2008 to July 2015. Clinical characteristics, such as features of abdominal pain, etiologies, image data, levels of serum amylase and lipase, and physical development data were extracted from electronic medical records. The comparison between groups based on etiology or with normal control was performed with student′s t test. Results The age of first episode was (8.2±3.7) years. There were 61 (65%) children diagnosed with idiopathic CP, and 25 (27%) with anatomic abnormalities. The age of onset in the group with anatomic abnormalities was lower than that in the idiopathic CP group ((6.3 ± 3.5) vs. (8.9 ± 3.4) years, t=3.211, P=0.002). There were 51 (54%) patients with serum amylase elevation, 41(44%) patients with lipase elevation, and 35 (37%) with elevation in both. The questionnaire showed that 28 out of 30 children had moderate to severe abdominal pain. The patients′ weight standard score (SDS) was significantly lower than the overall average in normal control (-0.4±1.1 vs. 0, t=-3.308, P=0.001). Meanwhile, the mean level of insulin like growth factor‐1 (IGF‐1) SDS of 35 children was significantly decreased (-1.8 ± 1.8 vs. 0, t=-6.136, P<0.01). There were 69% (37/54) patients diagnosed by magnetic resonance cholangiopancreatography (MRCP) combined with magnetic resonance imaging (MRI), higher than that diagnosed by abdominal ultrasound (29%, 27/94). Conclusions Idiopathic CP and anatomic abnormalities were the two main etiologies. Normal level of serum amylase and lipase or negative finding of ultrasound cannot exclude CP, while MRCP and MRI should be considered to improve CP diagnostic rate. It is noteworthy that growth delay would happen in children with CP history.

Objective To evaluate the clinical value and safety of endoscopic retrograde cholangiopancreatog-raphy(ERCP)in children with pancreaticobiliary diseases. Methods Retrospective review was conducted for the data of 196 patients younger than 18 years old who underwent ERCP between January 2008 and June 2016 at Shanghai Rui-jin Hospital Affiliated to School of Medicine,Shanghai Jiaotong University. The data of indications,pathogenesis,thera-py,complications were collected and the relationship between ERCP treatment methods and post - operation complica-tions was analyzed. Results A total of 314 ERCP procedures were performed on 196 patients,with the success rate of 99. 0％ . There were 94 boys and 102 girls with the median age of (8. 7 ± 3. 7)years old(ranged 1. 1 - 16. 8 years old) at time of procedure. Indications included pancreatic diseases(156 cases)and bile duct diseases(40 cases). The ERCP findings were classified as follows:chronic pancreatitis(114 cases),acute recurrent pancreatitis(28 cases),bile duct stone(19 cases),acute pancreatitis(12 cases),cholangiectasis(8 cases),cholangitis(5 cases),congenital biliary dila-tion(5 cases)and other pancreaticobiliary. Furthermore,45. 9％ of the patients were proved to have structural abnor-malities after operation. The most common bile duct diseases were malfusion of pancreatobiliary ducts(60. 0％),and pancreas cleavage was the most common cause of recurrent pancreatitis,accounting for 22. 4％ . The total post - ERCP complication rate was 14. 3％,including 41 cases(13. 0％)mild to moderate post - ERCP pancreatitis,4 cases(1. 3％) gastrointestinal bleeding. All cases were cured by medical treatment except that one cases with duodenal minor papilla wound bleeding underwent emergent endoscopic hemostasis. No other serious complications occurred such as bile duct in-fection,postoperative perforation and severe pancreatitis related to ERCP. Statistical analysis showed that multiple repeated operations were the protective factor for post - ERCP pancreatitis and pancreatic stone removal was the risk factor. Conclusions The diagnostic and therapeutic utility of ERCP for pediatrics with pancreaticobiliary diseases is effective and safe.

Objective To investigate the incidence of extra intestinal organ damage in infants with acute rotavirus (RV) infection,the relative risk factors in patients with extra intestinal organ damage,the significance of procalcitonin(PCT)in those infants with multiple organ injury.Methods One hundred and three infants with acute diarrhea whose rotavirus antigens were positive and 65 negative ones were divided into two groups.The differences between these two groups in incidences of extra intestinal organ damage were analyzed.Meanwhile,variables from the clinical data that may lead to extra intestinal organ damage were analyzed.Then,the relationship of multiple organ damage and serum concentration of PCT was also analyzed.Results There were significant differences between positive group and negative group in the rates of respiratory system injury,myocardial damage and hepatic involvement (P ＜ 0.05).High fever was the only high risk factor in myocardial damage through multi factor Logistic regression analysis.There were also significant differences among the group with multiple organ damage and only one extra intestinal organ damage and no extra intestinal organ damage in serum concentration of PCT(P ＜ 0.05).Conclusion It is common to be attacked by extra intestinal organ damage in infants with acute rotavirus infection.High fever is the risk factor for RV enteritis complicated with myocardial damage.The elevation of PCT concentration suggest that multiple organ injury out of the intestinal tract may take place in infants with acute RV infection.

Celiac disease(CD) is a chronic intestinal malabsorption syndrome by ingestion of wheat bran material in a susceptible population which is immune-mediated.At present,the incidence of CD in North America and Europe has reached about 1％-3％,the disease is considered to be very rare in China,but now some studies have confirmed the existence of the disease.Children suffering from CD can lead to failure in growth and development,and patients can be significantly improved by gluten-free diet.Therefore,early diagnosis and timely treatment is great significance.

Objective To investigate the imbalance of peripheral Th17 cells(Th17)and regulatory T cells(Treg)in children with allergic rhinitis(AR)and bronchial asthma(BA)and its clinical significance.Methods A total of 25 children with simple AR(AR group),25 children with simple BA(BA group)and 25 children with AR complicated with BA(AR+BA group)were selected.Another 25 healthy children were selected as control group at the same time.The levels of Th17 cells and Treg cells in peripheral blood,immunoglobulin E(IgE),transforming growth factor β1(TGF-β1),percentage of forced expiratory volume in one second in predicted value(FEV1％)and levels of serum IL-6,IL-17,IL-23 and IL-10 were compared among four groups.The correlations between IgE,FEV1％and Th17,Treg,TGF-β1,IL-17 in children with AR complicated with BA were analyzed.Results There were significant differences in peripheral blood Th17 cells,Treg cells,IgE,TGF-β1 and FEV1％between AR group,BA group,AR+BA group and the control group(P<0.05).IL-17 level was significantly higher in AR+BA group than AR group and BA group(P<0.05).Correlation analysis showed that IgE was positively correlated with levels of Th17 and IL-17,and negatively correlated with Treg and TGF-β1(P<0.05).Conclusion There is imbalance of Th17 and Treg cells in children with AR and BA.Their expression are correlated with IgE and FEV1％.