2017年 · 第55卷第07期

The human gut microbial flora consists of 1×10¹⁴It is composed of 1,000 to 1,500 bacteria, 10 times the total amount of human cells and 150 times the total amount of human genes. Normal intestinal flora plays an important role in maintaining human health and nutrition. It has the functions of anti-infection, promoting digestion and absorption of nutrients, obtaining energy, inducing host immune response, regulating and maintaining intestinal barrier function^[1]。 With the in-depth research on intestinal flora, microecological preparations prepared according to the principle of microecology have received widespread attention, including probiotics preparations, which refer to preparations containing a sufficient number of non-pathogenic specific viable bacteria that are beneficial to the health and/or physiological function of the host, and maintain microecological balance by improving the microbial flora on the surface of mucosa such as the intestinal tract of the host; prebiotics preparations refer to preparations of substances capable of selectively stimulating the growth and reproduction of one or several beneficial bacteria in the intestine without being digested by the host; synbiotics preparation refers to a combination of probiotics and prebiotics^[2]； postbiotics preparations refer to the bacterial components and metabolites of probiotics^[3]。

human milk oligosaccharides (HMO), a prebiotic component in breast milk, are the third largest solid component in breast milk after lactose and fat. HMO is not decomposed by digestive enzymes in the intestine, but acts as a substrate to stimulate and/or activate the growth and reproduction of intestinal bacteria, and plays a role in protecting against intestinal pathogenic microorganism infection and maintaining the balance of intestinal microecology^[1]。 Significant differences in intestinal flora composition have been demonstrated between breast-fed and standard formula-fed infants. The intestinal flora composition of infants fed with appropriate amounts of prebiotics added to formula milk is closer to that of breastfed infants^[2]。 Therefore, the role of prebiotics on the intestinal health of infants has received widespread attention.

Food allergy is a kind of adverse food reaction, which refers to one or more specific food ingredients that sensitize the body after entering the human body, and repeatedly entering it can lead to abnormal immune response of the body, causing physiological dysfunction and/or tissue damage, and then causing a series of clinical symptoms. The incidence of food allergy in children ranges from 0.02% to 8%, which varies according to age, region and allergen^[1]。 Its symptoms are non-specific and involve the digestive system, respiratory system, skin, cardiovascular system and nervous system, etc. Among them, 60% of children's food allergies involve the digestive system, and in severe cases, they can lead to growth retardation, anemia and hypoalbuminemia^[2]。 This consensus aims to standardize the diagnosis and management of such diseases.

The child was a 13-year-old male. The main reasons were repeated oral albuginea and rash with respiratory tract infection for 13 years, growth retardation for 12 years, repeated cytopenia for 6 years, and aggravation for 2 months. Two months after birth, the child began to repeatedly develop bilateral white membranous buccal mucosa, hard crusty rash on the chest and back, and bronchopneumonia (the result of multiple sputum cultures was Candida albicans). It is considered as chronic cutaneous and mucosal candidiasis and respiratory fungal infection. Antifungal treatments are effective. The child still has pulmonary abscess and bronchiectasis in the lungs. The child was found to be short at the age of 1 year and 6 months. So far, the height and weight of the child are still lower than the third percentile of normal height and weight of children of the same age. Thyroid function showed decreased triiodothyronine and thyroxine, increased thyroid stimulating hormone (TSH), and exogenous thyroxine supplementation was effective. From the age of 7, there was repeated cytopenia, and the platelets could rise to normal after gamma globulin and hormone treatment, but the anemia did not improve. Routine blood examination 2 months before admission showed moderate reduction in hemoglobin, reticulocytes, moderate to severe reduction in platelets, and normal white blood cells, which was not diagnosed and treated. The child's parents are not close relatives, the child is the sixth child and the sixth child, and there are 5 sisters, all of whom are in good health. The child's maternal grandfather died of esophageal cancer, and there was no abnormality in Yu family's history.

A male child, 4 months old and 27 days old, was admitted to Zhengzhou Children's Hospital due to "runny nose for 3 days, poor spirit for 2 days and shortness of breath for 1 day". The child developed runny nose 3 days before admission, and no special treatment was given. Poor mental response occurred 2 days before admission, and he went to the local hospital for fluid rehydration and acid correction treatment for 1 day. One day ago, the child developed shortness of breath, without cough, asthma, fever, vomiting and diarrhea. For further treatment, (1) metabolic acidosis (genetic metabolic disease?), (2) severe pneumonia? Admission. After the illness, the child's spirit, diet and night sleep are not good, and the defecation and defecation are normal. The child was the second birth and the second birth, with a full-term natural delivery, with a birth weight of 4.1 kg. He was breastfed after birth without supplement food, and his growth and development before admission were consistent with those of children of the same age. Past physical health, no similar medical history. Parents are not intimate married, 1 brother, 7 years old, in good health. Family history of genetic disease denied.

Case 1: A 34-day-old female with a gestational age of 34 weeks and a birth weight of 2 820 g was hospitalized in a local hospital due to "premature respiratory distress syndrome (RDS), patent ductus arteriosus (PDA) and persistent pulmonary hypertension". She was transferred to the Children's Hospital affiliated to Zhejiang University School of Medicine 34 days after birth in March 2015 due to "difficulty in withdrawal". She was admitted for physical examination. Auxiliary examination: Thyroid stimulating hormone (TSH)>150 mU/L, admission cardiac ultrasound showed "pulmonary artery systolic pressure 132.46 mmHg (1 mmHg =0.133 kPa), ejection fraction (EF) 0.50, left ventricular systolic function decreased, right heart large"; Abdominal B-ultrasound showed "several hypoechoic light clusters diffusely distributed in hypoechoic areas and thickening of hepatic veins". Abdominal CT scan plus enhancement showed hepatomegaly (4 cm below the costs) and multiple low-density shadows in the liver. The lesions on enhanced scan showed "progressive and centripetal enhancement". Admission diagnosis: Congenital heart disease: PDA, atrial septal defect, severe pulmonary hypertension, cardiac insufficiency; Infantile hepatic hemangioendothelioma (IHHE). After admission, he was given ventilator-assisted ventilation. Medical treatment included propranolol hydrochloride (trade name: propranolol) 0.6 mg/ (kg·d), sildenafil 2 mg/ (kg·d) gradually increased to 8 mg/ (kg·d), and milrinone 0.5 μ g/ (kg·min). Hepatic artery ligation was performed on the 9th day of admission. Two weeks after operation, the liver tumor shrank slightly (the liver shrank to 3.8 cm subcostal), and the pulmonary artery pressure dropped to 51.7 mmHg at two weeks after operation, but finally died of "decompensated heart failure, severe pulmonary hypertension complicated by infection".

The patient, a 4-year-old and 11-month-old girl, went to Beijing Children's Hospital in May 2016 due to "paroxysmal event of 4 years and 2 months". Four years and two months before admission (9 months of age), episodic events occurred, which were manifested as binocular gaze, lip smacking several times, and slight stiffness of limbs, which lasted for 1 to 3 s and resolved spontaneously, with attacks of 5 to 10 times a day. Standing or sitting attacks may appear to bend down or fall to the ground. There is no consciousness disorder at the time of attack, and can make eye contact or simple verbal communication. The attack has no inducement and irregularity, and all occurred in the waking period. He was diagnosed with "epilepsy (absence seizure)" in another hospital, and was treated with various anti-epileptic drugs orally, and was treated with minimally invasive surgery during the drug administration 2 years before admission (details unknown). The attacks of children gradually worsened, each attack lasted 10-20 s, and the frequency was 10-20 times a day. There was no discomfort between episodes. There was no special pregnancy of the mother of the child, perinatal period, feeding history and family history of the child. Children have backward intelligence and motor development since childhood. They raise their heads at 4 months, turn over at 6 months, sit alone at 10 months, stand alone at 18 months, are called "mom and dad" at 18 months, and walk alone at 24 months. Now the walking gait between attacks is OK, can speak simple sentences, and articulation is clear.

Eosinophilic esophagitis (EoE) is a chronic immune inflammatory disease of the esophagus characterized by esophageal eosinophil infiltration. At present, it is considered that the diagnostic value of esophageal histopathological examination with eosinophil count ≥15/high power field (HP) is significant^[1]。 Diagnostic criteria proposed in the United States in 2013^[2]It emphasizes that gastroesophageal reflux disease (GERD), proton pump inhibitor (PPI) -sensitive eosinophilia and other diseases should be ruled out. However, in clinical practice, it is often difficult to meet all criteria at the same time. Pediatric EoE patients have diverse clinical manifestations, lack of specificity, and are easily misdiagnosed and missed.

Childhood inflammatory bowel disease (IBD) is a kind of chronic intestinal inflammatory disease with unknown etiology and pathogenesis. The current global incidence of IBD in children is (2.5 to 11.4) /100 000, accounting for 10% of the total incidence of IBD, with an estimated prevalence of 58/100 000^[1,2]。 In recent years, the incidence of IBD in children in China and other Asian countries has been on the rise^[3,4]。 At present, the diagnosis of IBD in children requires a combination of clinical manifestations, laboratory and radiological examinations, endoscopic and pathological examinations, and the exclusion of intestinal inflammation caused by other reasons with similar clinical manifestations. In most cases, the diagnosis of IBD in children relies on endoscopy and biopsy. Despite multiple diagnostic methods, 20% of children have colonic lesions with an unclear diagnosis and are uncertain enteritis^[5]。 Numerous basic and clinical studies have found that the detection of serological markers plays an important role in the diagnosis of IBD in children, and it is also important for the differential diagnosis of IBD and non-IBD, Crohn's disease (CD) and ulcerative colitis (UC) in children^[6,7]。 The research progress of serological markers related to IBD in children is reviewed as follows.

The study design protocol with the highest level of evidence in evidence-based medicine among clinical studies is a randomized controlled trial (RCT). However, due to a series of problems such as ethics, it is more difficult to carry out RCT in pediatric research than in adult patients, and children, especially their families, have less acceptance of such research designs. In order to improve the quality of research, researchers often hope to adopt the research design scheme with high scientific and good feasibility, and cluster randomized trial is a good choice for pediatric researchers.